EP4493151A2 - Compositions possédant une biodisponibilité améliorée d'agents thérapeutiques et leurs utilisations - Google Patents

Compositions possédant une biodisponibilité améliorée d'agents thérapeutiques et leurs utilisations

Info

Publication number
EP4493151A2
EP4493151A2 EP23710760.2A EP23710760A EP4493151A2 EP 4493151 A2 EP4493151 A2 EP 4493151A2 EP 23710760 A EP23710760 A EP 23710760A EP 4493151 A2 EP4493151 A2 EP 4493151A2
Authority
EP
European Patent Office
Prior art keywords
weight
unsaturated
saturated
mixture
triglycerides
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23710760.2A
Other languages
German (de)
English (en)
Inventor
Daniel Gooding
John Brew
Robin M. Bannister
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Trx Biosciences Ltd
Original Assignee
Trx Biosciences Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/EP2022/058180 external-priority patent/WO2022207580A2/fr
Application filed by Trx Biosciences Ltd filed Critical Trx Biosciences Ltd
Publication of EP4493151A2 publication Critical patent/EP4493151A2/fr
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/148—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/5123—Organic compounds, e.g. fats, sugars

Definitions

  • Oral delivery of a therapeutic compound is the most preferred route of administration and account for eighty percent of all the pharmaceutical compositions on the market.
  • the underlying premise of traditional oral delivery is that the therapeutic compound must first be released from the composition into the gastrointestinal fluids being absorbed by capillaries lining the duodenum of the small intestine and then distributed systemically by the bloodstream.
  • the effectiveness of oral delivery typically relies on the pharmacokinetic properties of the pharmaceutical composition and the therapeutic compound formulated therein, with the amount of therapeutic compound released from the pharmaceutical composition (dissolution rate) and the amount of the therapeutic compound absorbed into systemic circulation and made available to the body (or bioavailability) being two primary critical factors.
  • hydrophilic therapeutic compounds the formulation challenges are different. Although these compounds are readily soluble in the aqueous gastrointestinal environment, many are poorly absorbed, due to poor membrane permeability and/or enzymatic degradation. Many solid dosage formulations of hydrophilic therapeutic compounds exhibit poor or no absorption of the therapeutic compounds.
  • One approach to improve the pharmacokinetics of a pharmaceutical composition comprising hydrophobic therapeutic compound has been the requirement to ingest the pharmaceutical composition with a high fat content meal to facilitate absorption in the small intestine and thus increase its bioavailability.
  • Ingestion of the meal triggers the digestive process in the stomach which includes release of bile from the gall bladder into the duodenum, where it breaks down and absorbs fats from food.
  • the absorption of the therapeutic compound that is released is enters the systemic circulation in higher amounts due to the concomitant absorption of fats from the meal.
  • phospholipid-based formulations including macroemulsion, microemulsion, self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), self-nanoemulsifying drug delivery systems (SNEDDS), solid-lipid nanoparticle (SLN), liposomes and lipoplexes.
  • SEDDS self-emulsifying drug delivery systems
  • SMEDDS self-microemulsifying drug delivery systems
  • SNEDDS self-nanoemulsifying drug delivery systems
  • SSNEDDS solid-lipid nanoparticle
  • liposomes and lipoplexes solid-lipid nanoparticle
  • compositions disclosed herein are formulated to rely on physiological lipid digestion and absorption systems to achieve absorption and enhanced efficacy and increase bioavailability of therapeutic compounds to better facilitate treatment of a disease or disorder.
  • formulations are not only applicable to highly lipophilic therapeutic compounds but also provide a means to increase the solubility of therapeutic compounds that are generally less soluble in both aqueous and lipid matrices.
  • a therapeutic compound disclosed herein can be a hydrophilic therapeutic compound, a hydrophobic therapeutic compound, or a pharmaceutical active agent or ingredient, a diagnostic agent or ingredient, a cosmeceutical active agent or ingredient, or a nutraceutical active agent or ingredient.
  • a glycerolipid disclosed herein includes hard fats and liquid fats.
  • a hard fat is a glycerolipid that is solid at 18°C and includes triglycerides.
  • a liquid fat is a glycerolipid that is liquid at 18°C and also includes partially hydrolyzed glycerolipids and monoglycerides.
  • Digestion enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C14-24 fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives with a polyhydroxylated head group, one or more steroidal surfactants, or any combination thereof.
  • a composition disclosed herein may further comprise one or more pharmaceutically- acceptable stabilizing agents.
  • a pharmaceutic composition for use in treating a disease or disorder, the pharmaceutic composition comprising a) one or more therapeutic compounds, b) one or more glycerolipids, and c) one or more digestion enhancers.
  • a therapeutic compound disclosed herein can be a hydrophilic therapeutic compound, a hydrophobic therapeutic compound, or a pharmaceutical active agent or ingredient, a diagnostic agent or ingredient, a cosmeceutical active agent or ingredient, or a nutraceutical active agent or ingredient.
  • a glycerolipid disclosed herein includes hard fats and liquid fats.
  • a hard fat is a glycerolipid that is solid at 18°C and includes triglycerides.
  • a liquid fat is a glycerolipid that is liquid at 18°C and also includes partially hydrolyzed glycerolipids and monoglycerides.
  • Digestion enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C14-24 fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives with a polyhydroxylated head group, one or more steroidal surfactants, or any combination thereof.
  • a composition disclosed herein may further comprise one or more pharmaceutically-acceptable stabilizing agents.
  • FIGS. 1A-1H show representative PXRD spectra analyzing a disclosed pharmaceutical composition comprising fenofibrate with FIG. 1 A showing a representative PXRD spectra of a GELCURE® 43/01 standard; FIG. 1 B showing a representative PXRD spectra of a cholic acid standard; FIG. 1C showing a representative PXRD spectra of a fenofibrate standard; FIG. 1 D showing a representative PXRD spectra of a Vehicle standard; FIG. 1 E showing a representative PXRD spectra of a disclosed pharmaceutical composition comprising fenofibrate standard; FIG.
  • FIG. 1F showing a representative PXRD spectra of a fenofibrate standard superimposed over a representative PXRD spectra of a disclosed pharmaceutical composition comprising fenofibrate standard with asterisks above peak indicating relevant peak overlap
  • FIG. 1G showing a representative PXRD spectra of a cholic acid standard superimposed over a representative PXRD spectra of a Vehicle standard with asterisks above peak indicating relevant peak overlap
  • FIG. 1 H showing a representative PXRD spectra of a cholic acid standard superimposed over a disclosed pharmaceutical composition comprising fenofibrate standard with asterisks above peak indicating relevant peak overlap
  • FIGS. 2A-2B show representative UHPLC tracings of fenofibric acid levels in blood and brain with FIG. 2A shows a UHPLC tracing of fenofibric acid levels in blood after oral administration of 30 mg/kg of disclosed pharmaceutical compositions comprising fenofibrate; and FIG. 2B shows a UHPLC tracing of fenofibric acid levels in brain after oral administration of 30 mg/kg of disclosed pharmaceutical compositions comprising fenofibrate;
  • FIG. 3 shows a representative UHPLC tracing of mebendazole levels in blood after oral administration of 30 mg/kg of disclosed pharmaceutical compositions comprising mebendazole;
  • FIG. 4 shows a representative UHPLC tracing of olaparib levels in blood after oral administration of 30 mg/kg of disclosed pharmaceutical compositions comprising olaparib.
  • the present specification discloses pharmaceutical compositions formulated for oral delivery in a manner where the therapeutic compound present in the pharmaceutical composition is preferentially taken up into the lymphatic system.
  • the pharmaceutical compositions disclosed herein comprises one or more therapeutic compounds, one or more glycerolipids, and one or more digestion enhancers.
  • a glycerolipid disclosed herein facilitates dissolvement of a therapeutic compound disclosed herein into solution and/or acts as a stabilizing agent that prevents a disclosed therapeutic compound from precipitating out of the pharmaceutical composition.
  • a digestion enhancer disclosed herein increases the solubility of the one or more therapeutic compounds in the glycerolipid matrix, in conjunction with the glycerolipids, increases absorption of these compounds into the lymphatic system, and increases availability of these compounds to their therapeutic target.
  • a disclosed pharmaceutical composition formulated using one or more glycerolipids and one or more digestion enhancers disclosed herein increases bioavailability of a therapeutic compound minimally by maintaining higher levels of the therapeutic compound over extended time period as well as increasing the directed bio-distribution of the therapeutic compound to its therapeutic target. Furthermore, besides achieving the greatest amount of therapeutic compound exposure over time to its therapeutic target, in many cases, a disclosed pharmaceutical composition enables a therapeutic compound to also reach its maximum concentration in the shortest period of time. Overall, a disclosed pharmaceutical composition exhibits a superior pharmacokinetic and pharmacodynamic profiles over current formulations of the same therapeutic compound making the disclosed pharmaceutical compositions more effective and efficacious for its intended use.
  • enterocytes The luminal wall of the small intestine is lined with many projections called villi, each of which comprises intestinal cells called enterocytes. Enterocytes not only secrete enzymes that digest proteins (polypeptides), carbohydrates (polysaccharides), and fats (lipids) but these cells also absorbed the amino acids, monosaccharides and fatty acid breakdown products. Interestingly, however, enterocytes process these breakdown products differently with amino acids and monosaccharides being taken up by capillaries and transported systemically by the blood system and fatty acids being taken up by blind ended lymphatic vessels called lacteal and then transported systemically by the lymphatic system.
  • the disclosed pharmaceutical compositions take advantage of this differential processing by formulating therapeutic compounds that are preferentially processed by enterocytes in a manner where these compounds are taken up and transported int the lymphatic system.
  • Dietary lipids typically consumed by a mammal comprise 90% triglycerides as well as small amounts of cholesterol esters and phospholipids. Unlike proteins and carbohydrates, dietary lipids are hydrophobic molecules that cannot dissolve in the fluids present in the lumen of the small intestine and instead aggregate together to form fat globules. Pancreatic lipase is a water-soluble enzyme that cleaves ester bonds and breaks down lipid triglycerides into fatty acids and glycerol.
  • Bile contains amphipathic molecules such as bile salts including sodium cholate and sodium chenodeoxycholate, phospholipids including lecithin, as well as the hydrophobic steroid cholesterol.
  • bile When bile is excreted into the small intestine it mixes with the fat globules in a manner where bile salts and phospholipids intercalate with and break apart these structures into smaller units called emulsion droplets as well as recruits an amphipathic molecule called collapse.
  • Colipase is a protein co-enzyme that binds lipase to the emulsion droplets and stabilizes the enzyme in its active conformation, As such, emulsification greatly increases the surface area of which lipases can act upon triglycerides as well as increases its efficiency and catalytic rate thereby enabling sufficient amounts of lipid digestion to occur in the small intestine.
  • the resulting free fatty acids which are also hydrophobic and insoluble in the intestinal fluids, associate with the phospholipids from the bile to form tiny droplets called mixed micelles having a phospholipid and bile salt composition which encapsulates the free fatty acids.
  • Mixed micelles which are about 200 to 500 times smaller in size than emulsion droplets, fuse with the membranes of enterocytes where the free fatty acids enter the cytosol of these cells. Once inside the enterocytes, the free fatty acids are transported to the lumen of smooth endoplasmic reticulum and are transformed back into triglycerides are assembled with cholesterol and phospholipids into spherical lipid structures.
  • chylomicrons are then packaged is the Golgi apparatus and exit the basolateral side of the enterocytes via exocytosis. Since chylomicrons are too large to be taken up by blood capillaries, these lipoproteins enter the lymphatic system via the lacteal in a process that depends on Apo B-48. The chylomicrons then circulate through the lymph vessels and drain into the blood system via the thoracic duct bypassing the liver circulation.
  • chylomicrons are in the blood system, these lipoproteins travel to various extrahepatic tissues where their triglycerides are hydrolyzed by the activity of the lipoprotein lipase, allowing the released free fatty acids and glycerol to be absorbed by the tissues.
  • chylomicron remnants are formed and are taken up by the liver, thereby also transferring dietary fat to this organ.
  • the present specification discloses pharmaceutical compositions formulated for oral delivery in a manner where the fibrate present in the pharmaceutical composition is preferential taken up into the lymphatic system.
  • the pharmaceutical compositions disclosed herein comprises one or more fibrates, one or more glycerolipids, and one or more digestion enhancers.
  • a digestion enhancer disclosed herein increases the solubility of the one or more fibrates in the glycerolipid matrix, in conjunction with the glycerolipids, increases absorption of these compounds into the lymphatic system and increases availability of these compounds to their therapeutic target.
  • Natural digestion processes rely upon the secretion of bile onto the ingested gut contents and rely upon their mixing with the gut contents to initiate emulsification and access to other digestion processes such as the activity of lipases. These processes must be completed for the drug to be absorbed.
  • a full gall bladder response in relation to the ingestion of lipids will secrete up to 50-60 ml_ of bile into the duodenum.
  • the present invention relies upon the intimate mixing of digestion enhancers with the fibrate in the preparation of a pharmaceutical composition disclosed herein that can then be taken orally by the patient. The fibrate is then presented to the gut lumen in a form that is immediately ready for uptake.
  • the pharmaceutical compositions disclosed herein employ components that are the products of triglyceride digestion to mimic the conditions created by a high fat meal.
  • There formulations enable the one or more fibrates contained therein to be bundled along with the free fatty acids into micelles and absorbed by the enterocytes which then package the one or more fibrates into chylomicrons.
  • the fibrate loaded chylomicrons are then transported by the lymphatic system to their target cells where the fibrates are taken up by these cells to exert their beneficial effects.
  • the chylomicrons are being co-opted as a drug delivery system for the one or more fibrates contain in a pharmaceutical composition disclosed herein.
  • the disclosed pharmaceutical compositions provide a more consistent and predictable bioavailability of the one or more fibrates disclosed herein that could ever be achieved by reliance on a high fat meal.
  • a pharmaceutical composition disclosed herein delivers its fibrates via the lymphatic system.
  • the use of the lymphatic system to deliver fibrates is beneficial for several reasons.
  • the lymphatic system avoids pre-systemic metabolism that reduces the bioavailability of many fibrates administered using a traditional oral delivery approach.
  • first pass effect or first-pass metabolism a fibrate absorbed by the digestive system must first enter the hepatic portal system before reaching systemic circulation. While in the hepatic portal system, a fibrate can be metabolized by hepatic enzymes of the liver which reduce the amount of fibrate that enters systemic circulation.
  • lymphatic uptake system represents an attractive opportunity for the preferential delivery of drugs.
  • small water-soluble molecules that obey the rules for paracellular absorption are not ideal substrates for lymphatic uptake.
  • Additional highly lipophilic molecules which are often poorly and variably bioavailable even when absorbed by lymphatic uptake.
  • This invention uses a wide family of digestion enhancers in a lipidic delivery system, to allow both the small molecule Lipinski compliant drugs and the highly lipophilic drugs to be effectively delivered through the lymphatic uptake route.
  • the lymphatic route of administration can aid delivery of fibrates directly to its target cells, thereby increasing its bioavailability and decreasing its clearance rate.
  • fibrate loaded chylomicrons transported into the lymphatic system would drain into the thoracic artery and circulate throughout the body via the arterial system until reaching a capillary bed where the fibrate loaded chylomicrons extracavates into the surrounding tissue to be taken up by target cell.
  • lymphatic-based administration results in more fibrate being delivered to the various systems, organs, and tissues due to the avoidance of the hepatic portal system discussed above. Additionally, since more fibrate enters the general circulatory system, its elimination, i.e., metabolism and excretion, is prolonged, thereby decreasing the clearance rate of this compound which effectively increases its half-life.
  • Another advantage of the disclosed pharmaceutical compositions is the use of chylomicrons to selectively biodistribute the one or more fibrates contained therein to immune cells such as, e.g., macrophages and dendritic cells.
  • immune cells such as, e.g., macrophages and dendritic cells.
  • macrophages can take up chylomicrons.
  • macrophages circulating in the lymph and blood secrete lipoprotein lipase and chylomicrons are substrates for this enzymatic activity resulting in the uptake of chylomicron proteins and lipids, and by extension any fibrates contained within the chylomicrons.
  • the exogenous lipoprotein metabolism pathway through a series of processing events converts chylomicrons to LDL particles which become oxidized by ROS to create oxidized LDL particles.
  • FAT/CD36 scavenger receptor located on membrane of macrophages bind to and endocytose these oxidized LDL particles including any fibrates contained therein.
  • these fibrate-loaded macrophages will be directed to cells undergoing pathologic distress where the fibrates can be delivered to these distressed cells.
  • GALT gut-associated lymphoid tissue
  • these micelles can also be taken up via the macrophage lipoprotein lipase process discussed above.
  • compositions are also advantageous because the components used for its formulation mimic the signals that trigger bile and pancreatic lipoprotein lipase secretion, enhance the rate of micellular formation, and increase the enterocyte absorption rate of micelle above that achieved with the use of the digestion enhancers in the formulation alone. Such characteristics increase the speed and amount of fibrate entering the lymphatic system and thus its bioavailability.
  • fibrates are poorly water soluble or hydrophobic therapeutic compounds that heretofore have proven difficult to formulate in a therapeutically effective manner due to, e.g., their insolubility or instability in solution resulting in precipitation.
  • fibrates are poorly water soluble or hydrophobic therapeutic compounds that heretofore have proven difficult to formulate in a therapeutically effective manner due to, e.g., their insolubility or instability in solution resulting in precipitation.
  • a disclosed pharmaceutical composition comprising one or more fibrates dramatically increase the dissolution rate and bioavailability of these compounds.
  • Chylomicrons comprise membrane-bound proteins which function as ligands which associate with their cognate receptors located on the membrane surface of cells.
  • One such ligand of these large lipoprotein particles are proteins that interact with lipid transport proteins.
  • fibrate-loaded chylomicrons are shed for absorption, cells that express high levels of lipid transport proteins on the cellular membrane preferentially bind and internalize these lipoprotein particles.
  • the brain has high levels of lipid transport proteins on the cellular membrane allowing passage across the blood brain barrier, and other epithelial tissue such as the choroid plexus. This mechanism thereby increases the efficacy of these compounds.
  • lipid transport proteins on the cellular membrane include, immune, heart, adipose, hepatic, and cancer cells.
  • Heart cells express high levels of lipid transport proteins on their surface and we may therefore anticipate an increased cardiotoxicity for therapeutic compounds delivered through the lymphatic pathway.
  • cardiotoxicity of therapeutic compounds is commonly caused through a high Cmax concentrations of free compound, resulting in GPCR or ion channel related pathologies.
  • lipid delivery of therapeutic compounds can result in lower-than-expected cardiotoxicity as these targets are protected from high concentrations of free compounds, as they are only slowly released from the chylomicron phase.
  • the use of a pharmaceutical composition disclosed herein can also be associated with reduce cardiac side effects and diminished toxicity.
  • anti-inflammatory, antifibrotic, antimicrobial and bronchodilatory medications can be considered ling targeting through lymphatic delivery, using this technology.
  • the disclosed pharmaceutical compositions are unlike current surfactant-based formulations, such as, e.g., macroemulsion, microemulsion, self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), self-nanoemulsifying drug delivery systems (SNEDDS), solid-lipid nanoparticle (SLN), liposomes and lipoplexes.
  • the disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions, and as such avoid the side-effects associated with these formulations like destabilizing the membranes lining in the stomach causing irritation. Additionally, the disclosed pharmaceutical compositions avoid the manufacturing issues associated with current surfactant-based formulations, such as, e.g., formulation handling issues and no predictive in vitro testing. The disclosed pharmaceutical compositions also avoid the problems associated with current surfactant-based formulations include, e.g., in v/vo drug precipitation, limited lymphatic uptake, and lack of and oxidation of unsaturated fatty acids.
  • the disclosed pharmaceutical compositions completely bypass the dissolution phase of drug uptake resulting in significantly greater bioavailability of one or more fibrates contained therein.
  • the formulations disclosed herein are designed to avoid the formation of stable emulsions and when added to water, do not undergo spontaneous emulsification (exhibit the Ouzo Effect). Rather, when added to water these materials are clearly immiscible.
  • compositions disclosed herein are generally administered as a pharmaceutical acceptable composition.
  • pharmaceutical acceptable refers any molecular entity or composition refers any molecular entity or composition useful in preparing a pharmaceutical composition that is generally safe, non-toxic, and neither biologically nor otherwise undesirable and includes that which is acceptable for veterinary use as well as human pharmaceutical use.
  • pharmaceutically acceptable composition is synonymous with “pharmaceutical composition” and means the combination of one or more therapeutic compounds disclosed herein that are combined with one or more glycerolipids, one or more digestion enhances, and other components disclosed herein to form the product that is administered to an individual.
  • a pharmaceutical composition disclosed herein is useful for medical and veterinary applications.
  • a pharmaceutical composition may be administered to an individual alone, or in combination with other supplementary active ingredients, agents, drugs or hormones.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more glycerolipids, and c) one or more digestion enhancers.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more glycerolipids, c) one or more bile acids and/or one or more bile salts, one or more phospholipids, one or more free C14-24 fatty acid surfactants, or any combination thereof.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more glycerolipids, c) one or more bile acids and/or one or more bile salts; and d) one or more phospholipids.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more glycerolipids, c) one or more bile acids and/or one or more bile salts; d) one or more phospholipids; and e) one or more free C14-24 fatty acid surfactants.
  • one or more therapeutic compounds disclosed herein can comprise one or more hydrophilic therapeutic compounds, one or more poorly water soluble or hydrophobic therapeutic compounds, or any combination thereof.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more triglycerides, one or more partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, and c) one or more digestion enhancers.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more triglycerides, one or more partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and/or one or more bile salts, one or more phospholipids, one or more free C14-24 fatty acid surfactants, or any combination thereof.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more triglycerides, one or more partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and/or one or more bile salts; and d) one or more phospholipids.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more triglycerides, one or more partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and/or one or more bile salts; d) one or more phospholipids; and e) one or more free C14-24 fatty acid surfactants.
  • one or more therapeutic compounds disclosed herein can comprise one or more hydrophilic therapeutic compounds, one or more poorly water soluble or hydrophobic therapeutic compounds, or any combination thereof.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, and c) one or more digestion enhancers.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and/or one or more bile salts, one or more phospholipids, one or more free C14-24 fatty acid surfactants, or any combination thereof.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and/or one or more bile salts; and d) one or more phospholipids.
  • a pharmaceutical composition disclosed herein comprises a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and/or one or more bile salts; d) one or more phospholipids; and e) one or more free C14-24 fatty acid surfactants.
  • one or more therapeutic compounds disclosed herein can comprise one or more hydrophilic therapeutic compounds, one or more poorly water soluble or hydrophobic therapeutic compounds, or any combination thereof.
  • a pharmaceutical composition disclosed herein is formulated as an anhydrous solid, a solid dispersion, or a molecular dispersion. As such, the formulations of the disclosed pharmaceutical compositions lack any water. In addition, as discussed above, the disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions. As such, a pharmaceutical composition disclosed herein will maintain its hydrophobilc lipid characteristics when in an aqueous environment, behaving just like fats and oils and requiring the lipid digestive process to be broken down for absorption. Only when exposed to pancreatic juices from the small intestine will emulsification occur.
  • the one or more glycerolipids and the one or more digestion enhancers used are not sufficiently amphiphilic to initiate emulsification and require the action of bile secreted by the gall bladder during the digestion process in order for these components to contribute to the formation of micellar structures.
  • Another reason is that the bile acid, fatty acid surfactants, phospholipids, and any other digestion enhancer are all individually and in combination below the critical micellar concentration necessary for emulsification to occur.
  • a therapeutic compound is a compound that provides pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or animals.
  • a therapeutic compound includes both a small molecule therapeutic compound that is synthesized and a synthetic peptide, a biologic therapeutic compound manufactured in, extracted from, or semi synthesized from biological sources including vaccines, whole blood, blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living medicines used in cell therapy.
  • Non-limiting examples of a therapeutic compound include, a pharmaceutical active agent or ingredient, a diagnostic agent or ingredient, a cosmeceutical active agent or ingredient, and a nutraceutical active agent or ingredient.
  • a therapeutic compound disclosed herein may be used in the form of a pharmaceutically acceptable salt, solvate, or solvate of a salt, e.g. the hydrochloride. Additionally, therapeutic compound disclosed herein may be provided as racemates, or as individual enantiomers, including the R- or S-enantiomer.
  • the therapeutic compound disclosed herein may comprise a R- enantiomer only, a S-enantiomer only, or a combination of both a R-enantiomer and a S-enantiomer of a therapeutic compound.
  • a therapeutic compound disclosed herein can be a hydrophilic therapeutic compound or a hydrophobic therapeutic compound.
  • a pharmaceutical composition disclosed herein may comprises one or more therapeutic compounds based on Biopharmaceutics Classification System (BCS) Class l-IV drugs.
  • BCS Biopharmaceutics Classification System
  • the BCS is a scientific framework for classifying drug substances based on based on its minimum aqueous solubility in the pH range of 1 to 7.5, dose and human fraction absorbed or intestinal membrane permeability, see U.S. Department of Health and Human Services Food and Drug Administration Center for Evaluation and Research (CDER), Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, Guidance for Industry (2017), which is hereby incorporated by reference in its entirety.
  • the BCS When combined with the dissolution of the drug product, the BCS takes into account three major factors that govern the rate and extent of drug absorption from IR solid oral dosage forms: (1 ) dissolution, (2) solubility, and (3) intestinal permeability.
  • This system categorizes drugs into four classes according to their permeability and solubility.
  • BCS Class I drugs are therapeutic compounds that have high solubility and high permeable and are generally absorbed completely.
  • BCS Class II drugs are therapeutic compounds that have low solubility and high permeable and would be absorbed completely, if in solution.
  • BCS Class III drugs are therapeutic compounds that have high solubility and low permeable and have difficulty being absorbed completely, even though the agent is in solution (high dissolution rate).
  • BCS Class IV drugs are therapeutic compounds that have low solubility and low permeable and are difficult to get in solution and once in solution are difficult to get absorbed. Subclassification shave also been proposed based on whether a therapeutic compound from BCS Class I or III is an acid, a base or neutral, see Tsume, et al., The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC, Eur. J. Pharm. Sci. 57: 152-163 (2014), which is hereby incorporated by reference in its entirety.
  • IPD in vivo predictive dissolution
  • a pharmaceutical composition disclosed herein may comprises one or more BCS Class I therapeutic compounds, BCS Class II therapeutic compounds, BCS Class III therapeutic compounds, BCS Class IV therapeutic compounds, or any combination thereof.
  • a pharmaceutical composition disclosed herein may comprises one or more BCS Class I therapeutic compounds.
  • a pharmaceutical composition disclosed herein may comprises one or more BCS Class II therapeutic compounds.
  • a pharmaceutical composition disclosed herein may comprises one or more BCS Class III therapeutic compounds.
  • a pharmaceutical composition disclosed herein may comprises one or more BCS Class IV therapeutic compounds.
  • a pharmaceutical composition disclosed herein may comprises one or more hydrophilic therapeutic compounds.
  • a hydrophilic therapeutic compound disclosed herein includes amphipathic therapeutic compound, and are water soluble compounds with appreciable or substantial water solubility.
  • a hydrophilic therapeutic compound disclosed herein has an intrinsic water solubility (i.e., water solubility of the unionized form) of, e.g., at least 0.1 % by weight, at least 0.5 % by weight, at least 1 % by weight or, and more typically at least 10% by weight.
  • a pharmaceutical composition disclosed herein may comprises one or more hydrophobic therapeutic compounds.
  • a hydrophobic therapeutic compound disclosed herein includes lipophilic therapeutic compounds, and are poorly water-soluble compounds having little or no water solubility.
  • a poorly water soluble or hydrophobic therapeutic compound disclosed herein has an intrinsic water solubility(i. e. , water solubility of the unionized form) of, e.g., at most 1 % by weight, at most 0.5% by weight, at most 0.1 % by weight, and more typically at most 0.01 % by weight.
  • a therapeutic compound disclosed herein is a therapeutic compound comprising an organic acid functional group, such as, e.g., a carboxylic acid functional group or sulfonic acid functional group.
  • an organic acid functional group such as, e.g., a carboxylic acid functional group or sulfonic acid functional group.
  • examples of a disclosed therapeutic compound comprising an organic acid functional group include a free acid form of a therapeutic compound (/.e., a therapeutic compound having a free organic acid) and a salt form of a therapeutic compound (/.e., a therapeutic compound having an organic acid salt).
  • An organic acid salt form of a therapeutic compound includes any therapeutic compound associated with an alkali metal, such as, e.g., lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), or alkaline earth metal, such as, e.g., beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).
  • an alkali metal such as, e.g., lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr)
  • alkaline earth metal such as, e.g., beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).
  • a therapeutic compound disclosed herein is a therapeutic compound comprising an organic base functional group, such as, e.g. an amine functional group.
  • examples of a disclosed therapeutic compound comprising an organic base functional group include a therapeutic compound containing an organic base functional group capable of donating ions.
  • a therapeutic compound containing an organic base functional group capable of donating ions is a therapeutic compound containing an amine functional group capable of donating ions including, without limitation, a primary amine, a secondary amine, a tertiary amine, amide, amidine, amido, amino, imidate, imide, imine, imino, iminohydroxyl, and a quaternary salt.
  • Non-limiting examples of a therapeutic compound include those classified by the United States Pharmacopea (USP) including analgesics (including opioids and non-opioids), anesthetics, antibacterials (including antibiotics), anticonvulsants, antidementia agents, antidepressants, antidotes and antitoxins, antiemetics, antifungals, anti-inflammatory agents (including corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and nonsteroidal anti-inflammatory drugs (NSAIDs)), antimigraine agents, antimyasthenic agents, antimycobacterials, antineoplastics, antiparasitics, antiparkinson agents, antipsychotics, antivirals (including HIV antiretrovirals and direct-acting hepatitis C drugs), anxiolytic (antianxiety) agents, bipolar agents, blood glucose regulators (including insulin and other diabetes medications), blood products (including anticoagulants), cardiovascular agents (including beta-blockers.
  • USP United States Pharmacopea
  • ACE inhibitors and lipid management drugs such as statins and PPAR agonists), central nervous system agents (including amphetamines), dental and oral agents, dermatological (skin) agents, enzyme replacement agent, gastrointestinal agents (including H2 blockers and proton pump inhibitors), genitourinary (genital and urinary tract) agents, hormonal agents (adrenal, pituitary, prostaglandins, sex hormones, including estrogen, testosterone, and anabolic steroids, and thyroid), hormone suppressant (adrenal, parathyroid, pituitary, sex hormones, and thyroid), immunological agents, inflammatory bowel disease agents, metabolic bone disease agents, nootropic agents, ophthalmic agents, otic agents, respiratory tract agents (including antihistamines and bronchodilators), sedatives and hypnotics, skeletal muscle relaxants, and therapeutic nutrients, minerals, and electrolytes.
  • statins and PPAR agonists central nervous system agents (including amphetamines), dental and oral agents
  • Non-limiting examples of a therapeutic compound include those classified as 5-alpha-reductase inhibitors, 5-aminosalicylates, 5HT3 receptor antagonists, adamantane, adrenal cortical steroids, adrenal corticosteroid inhibitors, agents for hypertensive emergencies, agents for pulmonary hypertension, aldosterone receptor antagonists, alkylating agents, allergenics, alpha-glucosidase inhibitors, alternative medicines, amebicides, aminoglycosides, aminopenicillins, aminosalicylates, amphetamines, AMPA receptor antagonists, amylin analogs, analgesics, androgens, anabolic steroids, Angiotensin Converting Enzyme (ACE) inhibitors, angiotensin II inhibitors, angiotensin receptor blockers, anorexiants, antacids, antiadrenergic agents, antiandrogens, antianginal agents, antiarrhythmic agents, antiasthmatic agents, anti
  • pylori eradication agents H2 antagonists, hedgehog pathway inhibitors, hematopoietic stem cell mobilizer, heparin antagonists, heparins, HER2 inhibitors, herbal products, histone deacetylase inhibitors, hormones, hydantoin, hydrazide derivatives, immunologic agents, immunostimulants, immunosuppressive agents, impotence agents, incretin mimetics, inotropic agents, insulin, insulin-like growth factors, integrase strand transfer inhibitor, interferons, interleukin inhibitors, interleukins, intravenous nutritional products, investigational drugs, iodinated contrast media, iron products, ketolides, leprostatics, leukotriene modifiers, lincomycin derivatives, local injectable anesthetics, lymphatic staining agents, macrolide derivatives, macrolides, magnetic resonance imaging contrast media, malignancy photosensitizers, mast cell stabilizers, meglitinides, melanocort
  • a therapeutic compound disclosed herein may be a protein kinase inhibitor.
  • a protein kinase inhibitor is a type of enzyme inhibitor that blocks the action of one or more protein kinases.
  • Protein kinases are ubiquitous intracellular and cell surface proteins that play critical roles in cell signaling pathways involved in metabolism, injury responses, adaption, growth, and differentiation. They act by adding a phosphate group to a protein (phosphorylation), usually on a specific amino acid which often makes the protein or enzyme "active".
  • the human genome has more than 500 protein kinases and they can be classified as tyrosine, serine-threonine or nonspecific (both), based upon their amino acid specificity.
  • a tyrosine kinase inhibitor can be divided into two main families, receptor tyrosine kinase (RTK) inhibitors and non-receptor or cytoplasmic tyrosine kinase (nRTK) inhibitors.
  • RTK receptor tyrosine kinase
  • nRTK cytoplasmic tyrosine kinase
  • RTK inhibitors include RTK class I inhibitors (EGF receptor family) (ErbB family), RTK class II inhibitors (Insulin receptor family), RTK class III inhibitors (PDGF receptor family), RTK class IV inhibitors (VEGF receptors family), RTK class V inhibitors (FGF receptor family), RTK class VI inhibitors (CCK receptor family), RTK class VII inhibitors (NGF receptor family), RTK class VIII inhibitors (HGF receptor family), RTK class IX inhibitors (Eph receptor family), RTK class X inhibitors (AXL receptor family), RTK class XI inhibitors (TIE receptor family), RTK class XII inhibitors (RYK receptor family), RTK class XIII inhibitors (DDR receptor family), RTK class XIV inhibitors (RET receptor family), RTK class XV inhibitors (ROS receptor family), RTK class XVI inhibitors (LTK receptor family), RTK class XVII inhibitors (ROR receptor family), RTK class XVIII inhibitors (MuSK receptor
  • Nonlimiting examples of nRTK inhibitors include ABL nRTK inhibitors, ACK nRTK inhibitors, CSK nRTK inhibitors, FAK nRTK inhibitors, FES nRTK inhibitors, FRK nRTK inhibitors, JAK nRTK inhibitors, SRC nRTK inhibitors, SYK nRTK inhibitors, and TEC nRTK inhibitors.
  • a serine-threonine kinase (STK) inhibitor can be divided into two main families, receptor protein serine/threonine kinase (RSTK) inhibitors and non-receptor or cytoplasmic serine/threonine kinase (nRSTK) inhibitors.
  • RSTK receptor protein serine/threonine kinase
  • nRSTK non-receptor or cytoplasmic serine/threonine kinase
  • Nonlimiting examples of receptor protein serine/threonine kinase inhibitors include Polo kinase (PLK) inhibitors, Cyclin-dependent kinase (CDK) inhibitors, (RNA-polymerase)-subunit kinase (RPS6K) inhibitors, Mitogen-activated protein kinase (MAPK) inhibitors, MAPK kinase (MAPKK) inhibitors, MAPK kinase kinase (MAPKKK or MAP3K) inhibitors, Tau-protein kinase (TPK) inhibitors, non-specific serine/threonine protein kinase inhibitors, Pyruvate dehydrogenase kinase (PDK) inhibitors, Dephospho- (reductase kinase) kinase inhibitors, 3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase inhibitors, (isocitrate dehydrogena
  • Two exemplary RSTK inhibitors are a Rho-associated protein kinase (ROCK) kinase inhibitor including ROCK 1 inhibitors and ROCK 2 inhibitors, and MAPK kinase inhibitors including MAPK1 inhibitors, MAPK3 inhibitors, MAPK4 inhibitors, MAPK6 inhibitors, MAPK7 inhibitors, MAPK8 inhibitors, MAPK9 inhibitors, MAPK10 inhibitors, MAPK11 inhibitors, MAPK12 inhibitors, MAPK13 inhibitors, MAPK14 inhibitors, and MAPK15 inhibitors.
  • ROCK Rho-associated protein kinase
  • a therapeutic compound disclosed herein may be a poly ADP ribose polymerase (PARP) inhibitor.
  • PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). PARP inhibitors are used to treat cancer and are considered a potential treatment for acute lifethreatening diseases, such as stroke and myocardial infarction, as well as for long-term neurodegenerative diseases.
  • a PARP inhibitor is a PARP 1 inhibitor or a PARP 2 inhibitor.
  • Non-limiting examples of PARP inhibitors are iniparib, olaparib, niraparib, rucaparib, talazoparib, and veliparib.
  • a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in an amount of, e.g., about 0.05%, about 0.1%, about 1%, about 2.5%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, about 20%, about 22.5%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50% by weight.
  • a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in an amount of, e.g., at least 0.05%, at least 0.1%, at least 1%, at least 2.5%, at least 5%, at least 7.5%, at least 10%, at least 12.5%, at least 15%, at least 17.5%, at least 20%, at least 22.5%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% by weight.
  • a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in an amount of, e.g., at most 0.05%, at most 0.1%, at most 1%, at most 2.5%, at most 5%, at most 7.5%, at most 10%, at most 12.5%, at most 15%, at most 17.5%, at most 20%, at most 22.5%, at most 25%, at most 30%, at most 35%, at most 40%, at most 45%, or at most 50% by weight.
  • a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds disclosed herein in an amount of, e.g., about 0.05% to about 1%, about 0.05% to about 2.5%, about 0.05% to about 5%, about 0.05% to about 7.5%, about 0.05% to about 10%, about 0.05% to about 12.5%, about 0.05% to about 15%, about 0.05% to about 17.5%, about 0.05% to about 20%, about 0.05% to about 22.5%, about 0.05% to about 25%, about 0.05% to about 30%, about 0.05% to about 40%, about 0.05% to about 50%, about 0.1% to about 1%, about 0.1% to about 2.5%, about 0.1% to about 5%, about 0.1% to about 7.5%, about 0.1% to about 10%, about 0.1% to about 12.5%, about 0.1% to about 15%, about 0.1% to about 17.5%, about 0.1% to about 20%, about 0.1% to about 22.5%, about 0.1% to about 25%, about 0.1% to about 30%, about 0.1% to about 40%, about 0.05% to about 50%,
  • a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in a concentration of, e.g., about 25 mg/mL, about 30 mg/mL, about 35 mg/mL, about 40 mg/mL, about 45 mg/mL, about 50 mg/mL, about 60 mg/mL, about 65 mg/mL, about 70 mg/mL, about 75 mg/mL, about 100 mg/mL, about 125 mg/mL, about 150 mg/mL, about 175 mg/mL, about 200 mg/mL, about 225 mg/mL, about 250 mg/mL, about 275 mg/mL, about 300 mg/mL, about 325 mg/mL, about 350 mg/mL, about 375 mg/mL, about 400 mg/mL, about 425 mg/mL, about 450 mg/mL, about 475 mg/mL, about 500 mg/mL, about 525 mg/mL, about 550 mg/mL, about 575 mg/mL,
  • a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in a concentration of, e.g., at least 25 mg/mL, at least 30 mg/mL, at least 35 mg/mL, at least 40 mg/mL, at least 45 mg/mL, at least 50 mg/mL, at least 60 mg/mL, at least 65 mg/mL, at least 70 mg/mL, at least 75 mg/mL, at least 100 mg/mL, at least 125 mg/mL, at least 150 mg/mL, at least 175 mg/mL, at least 200 mg/mL, at least 225 mg/mL, at least 250 mg/mL, at least 275 mg/mL, at least 300 mg/mL, at least 325 mg/mL, at least 350 mg/mL, at least 375 mg/mL, at least 400 mg/mL, at least 425 mg/mL, at least 450 mg/mL, at least 475 mg/mL, at least 500 mg/mL, at
  • a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in a concentration of, e.g., at most 25 mg/mL, at most 30 mg/mL, at most 35 mg/mL, at most 40 mg/mL, at most 45 mg/mL, at most 50 mg/mL, at most 60 mg/mL, at most 65 mg/mL, at most 70 mg/mL, at most 75 mg/mL, at most 100 mg/mL, at most 125 mg/mL, at most 150 mg/mL, at most 175 mg/mL, at most 200 mg/mL, at most 225 mg/mL, at most 250 mg/mL, at most 275 mg/mL, at most 300 mg/mL, at most 325 mg/mL, at most 350 mg/mL, at most 375 mg/mL, at most 400 mg/mL, at most 425 mg/mL, at most 450 mg/mL, at most 475 mg/mL, at most 500 mg/mL, at
  • a pharmaceutical composition disclosed herein comprises one or more therapeutic compounds in a concentration of, e.g., about 25 mg/mL to about 50 mg/mL, about 25 mg/mL to about 75 mg/mL, about 25 mg/mL to about 100 mg/mL, about 25 mg/mL to about 125 mg/mL, about 25 mg/mL to about 150 mg/mL, about 25 mg/mL to about 200 mg/mL, about 25 mg/mL to about 250 mg/mL, about 25 mg/mL to about 300 mg/mL, about 25 mg/mL to about 350 mg/mL, about 25 mg/mL to about 400 mg/mL, about 25 mg/mL to about 450 mg/mL, about 25 mg/mL to about 500 mg/mL, about 25 mg/mL to about 550 mg/mL, about 25 mg/mL to about 600 mg/mL, about 50 mg/mL to about 100 mg/mL, about 50 mg/mL to about 150
  • a pharmaceutical composition disclosed herein may comprises one or more glycerolipids.
  • Glycerolipids are composed mainly of mono-, di-, and tri-substituted glycerols and are hydrophobic molecules having an HLB of less than 4.
  • One group of glycerolipids is the glycerides, where one, two, or all three hydroxyl groups of glycerol are each esterified using a fatty acid to produce monoglycerides, diglycerides, and triglycerides, respectively.
  • each hydroxyl groups of glycerol may be esterified by the same fatty acid or different fatty acids.
  • a monoglyceride disclosed herein may include a saturated or unsaturated fatty acid having a carbon length of C12-C24.
  • a diglyceride disclosed herein may include one saturated or unsaturated fatty acid having a carbon length of C12-C24, or two saturated or unsaturated fatty acids each having a carbon length of C12- C24.
  • a triglyceride disclosed herein may include one saturated or unsaturated fatty acid having a carbon length of Ci2-C24,two saturated or unsaturated fatty acids each having a carbon length of C12-C24, or three saturated or unsaturated fatty acids each having a carbon length of C12-C24.
  • Two types of glycerolipids are used in formulating one or more therapeutic compounds disclosed herein to produce a pharmaceutical composition disclosed herein.
  • One type is hard fats, namely glycerolipids that are solid at 18°C.
  • a disclosed hard fat or glycerolipid that is solid at 18°C has several purposes.
  • a hard fat complexes with a therapeutic compound disclosed herein, stabilizes it in a glycerolipid matrix that prevents the compound from precipitating out.
  • a hard fat disclosed herein triggers the lipid digestion process stimulating the release of bile from the gallbladder to enhance the emulsification of the administered pharmaceutical composition.
  • the hard fats present in the pharmaceutical composition serve as substrates for pancreatic lipase which breaks down these hard fats into glycerol and free fatty acids.
  • pancreatic lipase breaks down these hard fats into glycerol and free fatty acids.
  • the presence of these digested lipid molecules triggers their absorption, along with the associated therapeutic compound, by the enterocytes lining the lumen of the duodenum of the small intestine. Once internalized, the enterocytes subsequent process and distribute the free fatty acid/therapeutic compound mixture into the lymphatic system.
  • a disclosed hard fat or glycerolipid that is solid at 18°C do not have emulsion forming properties since these lipids does not exhibit a critical micelle concentration.
  • a disclosed hard fat or glycerolipid that is solid at 18°C is to prevent formulary components that do possess a critical micelle concentration from initiating emulsification by diluting these components to below their critical micelle concentration and providing an anhydrous environment that reduces the necessary interaction of these components to initiate emulsification.
  • the other type of glycerolipid used in formulating one or more therapeutic compounds disclosed herein is liquid fats or oils, namely glycerolipids that are liquid at 18°C.
  • the primary purposes of a disclosed liquid fat or glycerolipid that is liquid at 18°C is as a solvent that facilitates dissolvement of a therapeutic compound disclosed herein as well as a stabilizing agent that prevents a disclosed therapeutic compound from precipitating out of the glycerolipid matrix.
  • a disclosed liquid fat or glycerolipid that is liquid at 18°C do not have emulsion forming properties since these lipids does not exhibit a critical micelle concentration.
  • liquid fat or glycerolipid that is liquid at 18°C
  • formulary components that do possess a critical micelle concentration from initiating emulsification by diluting these components to below their critical micelle concentration and providing an anhydrous environment that reduces the necessary interaction of these components to initiate emulsification.
  • a pharmaceutical composition disclosed herein may include one or more glycerolipids in an amount of, e.g., about 20% by weight, about 25% by weight, about 30% by weight, about 35% by weight, about 40% by weight, about 45% by weight, about 50% by weight, about 55% by weight, about 60% by weight, about 65% by weight, about 70% by weight, about 75% by weight, about 80% by weight, about 85% by weight, about 90% by weight, or about 95% by weight.
  • a pharmaceutical composition disclosed herein may include one or more glycerolipids in an amount of, e.g., at least 20% by weight, at least 25% by weight, at least 30% by weight, at least 35% by weight, at least 40% by weight, at least 45% by weight, at least 50% by weight, at least 55% by weight, at least 60% by weight, at least 65% by weight, at least 70% by weight, at least 75% by weight, at least 80% by weight, at least 85% by weight, at least 90% by weight, or at least 95% by weight.
  • a pharmaceutical composition disclosed herein may include one or more glycerolipids in an amount of, e.g., at most 20% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 45% by weight, at most 50% by weight, at most 55% by weight, at most 60% by weight, at most 65% by weight, at most 70% by weight, at most 75% by weight, at most 80% by weight, at most 85% by weight, at most 90% by weight, at most 95% by weight, or at most 99% by weight.
  • a pharmaceutical composition disclosed herein may include one or more glycerolipids in an amount of, e.g., about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 25% to about 30%, about 25% to about 40%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 70%, about 25% to about
  • composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of saturated C10-C18 triglycerides, a mixture of saturated C10-C20 triglycerides, a mixture of saturated C10- C22 triglycerides, a mixture of saturated C10-C24 triglycerides, a mixture of saturated C12-C18 triglycerides, a mixture of saturated C12-C20 triglycerides, a mixture of saturated C12-C22 triglycerides, a mixture of saturated C12-C24 triglycerides, a mixture of saturated C14-C18 triglycerides, a mixture of saturated C14-C20 triglycerides, a mixture of saturated C14-C22 triglycerides, a mixture of saturated C14-C24 triglycerides, a mixture of saturated C14-C24
  • composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of unsaturated C10-C18 triglycerides, a mixture of unsaturated C10-C20 triglycerides, a mixture of unsaturated C10-C22 triglycerides, a mixture of unsaturated C10-C24 triglycerides, a mixture of unsaturated C12-C18 triglycerides, a mixture of unsaturated C12-C20 triglycerides, a mixture of unsaturated C12-C22 triglycerides, a mixture of unsaturated C12-C24 triglycerides, a mixture of unsaturated C14-C18 triglycerides, a mixture of unsaturated C14-C20 triglycerides, a mixture of unsaturated C14-C22 triglycerides, a mixture of uns
  • pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of saturated and unsaturated C10-C18 triglycerides, a mixture of saturated and unsaturated C10-C20 triglycerides, a mixture of saturated and unsaturated C10-C22 triglycerides, a mixture of saturated and unsaturated C10-C24 triglycerides, a mixture of saturated and unsaturated C12-C18 triglycerides, a mixture of saturated and unsaturated C12-C20 triglycerides, a mixture of saturated and unsaturated C12-C22 triglycerides, a mixture of saturated and unsaturated C12-C24 triglycerides, a mixture of saturated and unsaturated C14-C18 triglycerides, a mixture of saturated and unsaturated C14-C18 triglycerides, a mixture
  • a pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of triglycerides having a melting point of, e.g., about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, about 30°C, about 31 °C, about 32°C, about 33°C, about 34°C, about 35°C, about 36°C, about 37°C, about 38°C, about 39°C, about 40°C, about 41 °C, about 43°C, about 43°C, about 44°C, about 45°C, about 45°C, about 47°C, about 48°C, about 49°C, or about 50°C.
  • a pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of triglycerides having a melting point of, e.g., at least 25°C, at least 26°C, at least 27°C, at least 28°C, at least 29°C, at least 30°C, at least 31 °C, at least 32°C, at least 33°C, at least 34°C, at least 35°C, at least 36°C, at least 37°C, at least 38°C, at least 39°C, at least 40°C, at least 41 °C, at least 43°C, at least 43°C, at least 44°C, at least 45°C, at least 45°C, at least 47°C, at least 48°C, at least 49°C, or at least 50°C.
  • a pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of triglycerides having a melting point of, e.g., at most 25°C, at most 26°C, at most 27°C, at most 28°C, at most 29°C, at most 30°C, at most 31 °C, at most 32°C, at most 33°C, at most 34°C, at most 35°C, at most 36°C, at most 37°C, at most 38°C, at most 39°C, at most 40°C, at most 41 °C, at most 43°C, at most 43°C, at most 44°C, at most 45°C, at most 45°C, at most 47°C, at most 48°C, at most 49°C, or at most 50°C.
  • a pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of triglycerides having a melting point of, e.g., about 25°C to about 37°C, about 25°C to about 38°C, about 25°C to about 39°C, about 25°C to about 40°C, about 25°C to about 41 °C, about 25°C to about 42°C, about 25°C to about 43°C, about 25°C to about 44°C, about 25°C to about 45°C, about 25°C to about 46°C, about 25°C to about 47°C, about 25°C to about 48°C, about 25°C to about 49°C, about 25°C to about 50°C, about 28°C to about 37°C, about 28°C to about 38°C, about 28°C to about 39°C, about 28°C to about 40°C,
  • a pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of triglycerides in an amount of, e.g., about 10% by weight, about 15% by weight, about 20% by weight, about 25% by weight, about 30% by weight, about 35% by weight, about 40% by weight, about 45% by weight, about 50% by weight, about 55% by weight, about 60% by weight, about 65% by weight, about 70% by weight, or about 75% by weight.
  • a pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of triglycerides in an amount of, e.g., at least 10% by weight, at least 15% by weight, at least 20% by weight, at least 25% by weight, at least 30% by weight, at least 35% by weight, at least 40% by weight, at least 45% by weight, at least 50% by weight, at least 55% by weight, at least 60% by weight, at least 65% by weight, at least 70% by weight, or at least 75% by weight.
  • a pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of triglycerides in an amount of, e.g., at most 10% by weight, at most 15% by weight, at most 20% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 45% by weight, at most 50% by weight, at most 55% by weight, at most 60% by weight, at most 65% by weight, at most 70% by weight, at most 75% by weight, at most 80% by weight, at most 85% by weight, at most 90% by weight, at most 95% by weight, or at most 99% by weight.
  • a pharmaceutical composition disclosed herein may include one or more hard fats or glycerolipids that are solid at 18°C comprising, or consisting essentially of or consisting of a mixture of triglycerides in an amount of, e.g., about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of a mixture of mono-, di- and triglycerides.
  • pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of a mixture of unsaturated C10-C18 monoglycerides, C10-C18 diglycerides, and
  • C10-C18 triglycerides a mixture of unsaturated C10-C20 monoglycerides, C10-C20 diglycerides, and C10-C20 triglycerides, a mixture of unsaturated C10-C22 monoglycerides, C10-C22 diglycerides, and C10-C22 triglycerides, a mixture of unsaturated C10-C24 monoglycerides, C10-C24 diglycerides, and C10-C24 triglycerides, a mixture of unsaturated C12-C18 monoglycerides, C12-C18 diglycerides, and C12-C18 triglycerides, a mixture of unsaturated C12-C20 monoglycerides, C12-C20 diglycerides, and C12-C20 triglycerides, a mixture of unsaturated C12-C22 monoglycerides, C12-C22 diglycerides, and C12-C20 trigly
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of a mixture of saturated C10-C18 monoglycerides, C10-C18 diglycerides, and C10-C18 triglycerides, a mixture of saturated C10-C20 monoglycerides, C10-C20 diglycerides, and C10-C20 triglycerides, a mixture of saturated
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of a mixture of saturated and unsaturated C10-C18 monoglycerides, C10-C18 diglycerides, and C10-C18 triglycerides, a mixture of saturated and unsaturated C10-C20 monoglycerides, C10-C20 diglycerides, and C10- C20 triglycerides, a mixture of saturated and unsaturated C10-C22 monoglycerides, C10-C22 diglycerides, and C10-C22 triglycerides, a mixture of saturated and unsaturated C10-C24 monoglycerides, C10-C24 diglycerides, and C10-C24 triglycerides, a mixture of saturated and unsaturated C12-C18 monoglycerides, C12-C18 diglycerides, and
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of a mixture of mono-, di- and triglycerides having a melting point of, e.g., at most 15°C, at most 16°C, at most 17°C, at most 18°C, at most 19°C, or at most 20°C.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising or consisting essentially of or consisting of a mixture of mono-, di-, and/or triglycerides in an amount of, e.g., about 10% by weight, about 15% by weight, about 20% by weight, about 25% by weight, about 30% by weight, about 35% by weight, about 40% by weight, about 45% by weight, about 50% by weight, about 55% by weight, about 60% by weight, about 65% by weight, about 70% by weight, or about 75% by weight by weight.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising or consisting essentially of or consisting of a mixture of mono-, di-, and/or triglycerides in an amount of, e.g., at least 10% by weight, at least 15% by weight, at least 20% by weight, at least 25% by weight, at least 30% by weight, at least 35% by weight, at least 40% by weight, at least 45% by weight, at least 50% by weight, at least 55% by weight, at least 60% by weight, at least 65% by weight, at least 70% by weight, or at least 75% by weight.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising or consisting essentially of or consisting of a mixture of mono-, di-, and/or triglycerides in an amount of, e.g., at most 10% by weight, at most 15% by weight, at most 20% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 45% by weight, at most 50% by weight, at most 55% by weight, at most 60% by weight, at most 65% by weight, at most 70% by weight, or at most 75% by weigh.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising or consisting essentially of or consisting of a mixture of mono-, di-, and/or triglycerides in an amount of, e.g., about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 45%, about 20% to
  • composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of one or more monoglycerides.
  • a monoglyceride includes, without limitation, glycerol monomyristoleate, glycerol monopalmitoleate, glycerol monosapienate, glycerol monooleate, glycerol monoelaidate, glycerol monovaccenate, glycerol monolinoleate, glycerol monolinoelaidate, glycerol monolinolenate, glycerol monostearidonate, glycerol monoeicosenoate, glycerol monomeadate, glycerol monoarachidonate, glycerol monoeicosapentaenoate, glycerol monoerucate, glycerol monodocosahe
  • pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of unsaturated C10-C18 monoglycerides, unsaturated C10-C20 monoglycerides, unsaturated C10-C22 monoglycerides, unsaturated C10-C24 monoglycerides, unsaturated C12-C18 monoglycerides, unsaturated C12-C20 monoglycerides, unsaturated C12-C22 monoglycerides, unsaturated C12-C24 monoglycerides, unsaturated C14-C18 monoglycerides, unsaturated C14-C20 monoglycerides, unsaturated C14-C22 monoglycerides, unsaturated C14-C24 monoglycerides, unsaturated CIB-CIB monoglycerides, unsaturated C16-C20 monoglycerides, unsaturated C16-C22
  • pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of saturated C10-C18 monoglycerides, saturated C10-C20 monoglycerides, saturated C10-C22 monoglycerides, saturated C10-C24 monoglycerides, saturated C12-C18 monoglycerides, saturated C12-C20 monoglycerides, saturated C12-C22 monoglycerides, saturated C12-C24 monoglycerides, saturated C14-C18 monoglycerides, saturated C14-C20 monoglycerides, saturated C14-C22 monoglycerides, saturated C14-C24 monoglycerides, saturated CIB-CIS monoglycerides, saturated C16-C20 monoglycerides, saturated C16-C22 monoglycerides, saturated C16-C24 monoglycerides, saturated C18-C20 monoglycerides, saturated
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of a mixture of saturated and unsaturated C10-C18 monoglycerides, a mixture of saturated and unsaturated C10- C20 monoglycerides, a mixture of saturated and unsaturated C10-C22 monoglycerides, a mixture of saturated and unsaturated C10-C24 monoglycerides, a mixture of saturated and unsaturated C12-C18 monoglycerides, a mixture of saturated and unsaturated C12-C20 monoglycerides, a mixture of saturated and unsaturated C12-C22 monoglycerides, a mixture of saturated and unsaturated C12-C24 monoglycerides, a mixture of saturated and unsaturated C14-C18 monoglycerides, a mixture of saturated and unsaturated C14-C20 monoglycerides, a mixture of saturated and unsaturated C14
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of a monoiglyceride having a melting point of, e.g., at most 15°C, at most 16°C, at most 17°C, at most 18°C, at most 19°C, or at most 20°C.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising, or consisting essentially of or consisting of a monoglyceride having a melting point between, e.g., about 0°C to about 5°C, about 0°C to about 10°C, about 0°C to about 15°C, about 0°C to about 20°C, about 0°C to about 22°C, about 0°C to about 25°C, about 5°C to about 10°C, about 5°C to about 15°C, about 5°C to about 20°C, about 5°C to about 22°C, about 5°C to about 25°C, about 10°C to about 15°C, about 10°C to about 20°C, about 10°C to about 22°C, about 10°C to about 25°C, about 15°C to about 20°C, about 15°C to about 22°C, or about 15°C to about 25°C.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising or consisting essentially of or consisting of one or more monoglycerides in an amount of, e.g., about 10% by weight, about 15% by weight, about 20% by weight, about 25% by weight, about 30% by weight, about 35% by weight, about 40% by weight, about 45% by weight, about 50% by weight, about 55% by weight, about 60% by weight, about 65% by weight, about 70% by weight, or about 75% by weight.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising or consisting essentially of or consisting of one or more monoglycerides in an amount of, e.g. at least 10% by weight, at least 15% by weight, at least 20% by weight, at least 25% by weight, at least 30% by weight, at least 35% by weight, at least 40% by weight, at least 45% by weight, at least 50% by weight, at least 55% by weight, at least 60% by weight, at least 65% by weight, at least 70% by weight, or at least 75% by weight.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising or consisting essentially of or consisting of one or more monoglycerides in an amount of, e.g., at most 10% by weight, at most 15% by weight, at most 20% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 45% by weight, at most 50% by weight, at most 55% by weight, at most 60% by weight, at most 65% by weight, at most 70% by weight, or at most 75% by weight.
  • a pharmaceutical composition disclosed herein may include one or more liquid fats or glycerolipids that are liquid at 18°C comprising or consisting essentially of or consisting of one or more monoglycerides in an amount of, e.g., about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about
  • 20% to about 45% about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about
  • Commercially available liquid fats or glycerolipids that are liquid at 18°C include, without limitation, a hydrolyzed corn oil including glycerol monolinoleate (MAISINETM 35-1 , MAISINETM CC).
  • a hydrolyzed corn oil including glycerol monolinoleate comprises about 32% to 52% monoglycerides including glycerol monolinoleate, about 40% to 50% diglycerides, and about 5% to 30% triglycerides.
  • a pharmaceutical composition disclosed herein comprises any ratio of hard fats or glycerolipids that are solid at 18°C to liquid fats or glycerolipids that are liquid at 18°C that stabilizes one or more therapeutic compounds disclosed herein in a manner that prevents precipitation of the one or more therapeutic compounds.
  • a pharmaceutical composition disclosed herein comprises a hard fats or glycerolipids that are solid at 18°C to a liquid fats or glycerolipids that are liquid at 18°C ratio of, e.g., about 5:1, about 4:1 , about 3:1 , about 2:1 , or about 1 :1.
  • a pharmaceutical composition disclosed herein comprises a hard fats or glycerolipids that are solid at 18°C to a liquid fats or glycerolipids that are liquid at 18°C ratio of, e.g., about 5:1 to about 4:1, about 5:1 to about 3:1 , about 5:1 to about 2: 1 , about 5: 1 to about 1 :1 , about 4: 1 to about 3: 1 , about 4:1 to about 2: 1 , about 4: 1 to about 1 :1, about 3:1 to about 2: 1 , about 3:1 to about 1 : 1 , or about 2: 1 to about 1 :1.
  • a pharmaceutical composition disclosed herein comprises a hard fats or glycerolipids that are solid at 18°C to a liquid fats or glycerolipids that are liquid at 18°C ratio of, e.g., about 1 :5, about 1 :4, about 1 :3, or about 1 :2.
  • a pharmaceutical composition disclosed herein comprises a hard fats or glycerolipids that are solid at 18°C to a liquid fats or glycerolipids that are liquid at 18°C ratio of, e.g., about 1:5 to about 1 :4, about 1:5 to about 1 :3, about 1:5 to about 1 :2, about 1:5 to about 1 :1, about 1 :4 to about 1:3, about 1 :4 to about 1 :2, about 1 :4 to about 1 :1 , about 1:3 to about 1 :2, about 1 :3 to about 1 :1, or about 1:2 to about 1:1.
  • Digestion Enhancers e.g., about 1:5 to about 1 :4, about 1:5 to about 1 :3, about 1:5 to about 1 :2, about 1:5 to about 1 :1, about 1 :4 to about 1:3, about 1 :4 to about 1 :2, about 1 :4 to about 1 :1 , about 1:3 to about 1
  • a pharmaceutical composition disclosed herein may comprises one or more digestion enhancers.
  • the primary purposes of the one or more digestion enhancers are to enhance solubility of a therapeutic compound disclosed herein with the glycerolipid admixture, to enhance absorption of a therapeutic compound disclosed herein thereby improving the pharmacokinetics of the compound, and/or to improve availability and facilitate selected bio-distribution of a therapeutic compound disclosed herein thereby improving the pharmacodynamics of the compound.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes one or more bile acids. In some embodiments, a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes cholic acid.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes one or more C14-C24 free fatty acids. In some embodiments, a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes one or more C14-C20 free fatty acids. In some embodiments, a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes an oleic acid, a steric acid, or a linoleic acid. In some embodiments, a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes one or more C14-C24 free fatty acid surfactants. In some embodiments, a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes one or more C14-C20 free fatty acid surfactants. In some embodiments, a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes a sodium oleate, a sodium stearate, and/or a sodium linoleate.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more bile acids disclosed herein; and 2) one or more C14-C24 free fatty acids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) a cholic acid disclosed herein; and 2) one or more C14-C20 free fatty acids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) a cholic acid disclosed herein; and 2) an oleic acid, a steric acid, or a linoleic acid.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more bile acids disclosed herein; 2) one or more C14-C24 free fatty acids disclosed herein; and 3) one or more C14-C24 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) a cholic acid disclosed herein; 2) one or more C14-C20 free fatty acids disclosed herein; and 3) one or more C14-C20 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1) a cholic acid disclosed herein; 2) an oleic acid, a steric acid, and/or a linoleic acid; and 3) a sodium oleate, a sodium stearate, and/or a sodium linoleate.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more bile acids disclosed herein; and 2) one or more phospholipids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) a cholic acid disclosed herein; and 2) one or more phospholipids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more C14-C24 free fatty acids disclosed herein; and 2) one or more phospholipids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more C14-C20 free fatty acids disclosed herein; and 2) one or more phospholipids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) an oleic acid, a steric acid, and/or a linoleic acid; and 2) one or more phospholipids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more bile acids disclosed herein; 2) one or more C14-C24 free fatty acids disclosed herein; and 3) one or more phospholipids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more bile acids disclosed herein; 2) one or more C14-C20 free fatty acids disclosed herein; and 3) one or more phospholipids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1) a cholic acid disclosed herein; 2) an oleic acid, a steric acid, and/or a linoleic acid; and 3) one or more phospholipids disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more bile acids disclosed herein; 2) one or more phospholipids disclosed herein; and 3) one or more C14-C24 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1) a cholic acid disclosed herein; 2) one or more phospholipids disclosed herein; and 3) one or more C14-C20 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) a cholic acid disclosed herein; 2) one or more phospholipids disclosed herein; and 3) a sodium C14-C20 free fatty acid disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) a cholic acid disclosed herein; 2) one or more phospholipids disclosed herein; and 3) a sodium oleate, a sodium stearate, and/or a sodium linoleate.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more C14-C24 free fatty acids disclosed herein; 2) one or more phospholipids disclosed herein; and 3) one or more C14-C24 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1) one or more C14-C20 free fatty acids disclosed herein; 2) one or more phospholipids disclosed herein; and 3) one or more C14-C20 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) an oleic acid, a steric acid, and/or a linoleic acid; 2) one or more phospholipids disclosed herein; and 3) one or more sodium C14-C20 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) an oleic acid, a steric acid, and/or a linoleic acid; 2) one or more phospholipids disclosed herein; and 3) a sodium oleate, a sodium stearate, and/or a sodium linoleate.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more bile acids disclosed herein; 2) one or more C14-C24 free fatty acids disclosed herein; 3) one or more phospholipids disclosed herein; and 4) one or more C14-C24 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) one or more bile acids disclosed herein; 2) one or more C14-C20 free fatty acids disclosed herein; 3) one or more phospholipids disclosed herein; and 4) one or more C14-C20 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1 ) a cholic acid disclosed herein; 2) an oleic acid, a steric acid, and/or a linoleic acid; 3) one or more phospholipids disclosed herein; and 4) one or more sodium C14-C20 free fatty acid surfactants disclosed herein.
  • a pharmaceutical composition disclosed comprises one or more digestion enhancers that includes 1) a cholic acid disclosed herein; 2) an oleic acid, a steric acid, and/or a linoleic acid; 3) one or more phospholipids disclosed herein; and 4) a sodium oleate, a sodium stearate, and/or a sodium linoleate.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more digestion enhancers in an amount of, e.g., about 1% by weight, about 2.5% by weight, about 5% by weight, about 7.5% by weight, about 10 % by weight, about 12.5% by weight, about 15 % by weight, about 17.5% by weight, about 20% by weight, about 22.5% by weight, about 25% by weight, about 30% by weight, about 35% by weight, about 40% by weight, about 45% by weight, about 50% by weight, about 55% by weight, about 60% by weight, about 65% by weight, about 70% by weight, about 75% by weight, or about 80% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more digestion enhancers in an amount of, e.g., at least 1% by weight, at least 2.5% by weight, at least 5% by weight, at least 7.5% by weight, at least 10 % by weight, at least 12.5% by weight, at least 15 % by weight, at least 17.5% by weight, at least 20% by weight, at least 22.5% by weight, at least 25% by weight, at least 30% by weight, at least 35% by weight, at least 40% by weight, at least 45% by weight, at least 50% by weight, at least 55% by weight, at least 60% by weight, at least 65% by weight, at least 70% by weight, at least 75% by weight, or at least 75% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more digestion enhancers in an amount of, e.g., at most 1% by weight, at most 2.5% by weight, at most 5% by weight, at most 7.5% by weight, at most 10 % by weight, at most 12.5% by weight, at most 15 % by weight, at most 17.5% by weight, at most 20% by weight, at most 22.5% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 45% by weight, at most 50% by weight, at most 55% by weight, at most 60% by weight, at most 65% by weight, at most 70% by weight, at most 75% by weight, or at most 80% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more digestion enhancers in an amount of, e.g., about 1% to about 2.5% by weight, about 1% to about 5% by weight, about 1% to about 10% by weight, about 1% to about 15% by weight, about 1% to about 20% by weight, about 1% to about 25% by weight, about 2.5% to about 5% by weight, about 2.5% to about 10% by weight, about 2.5% to about 15% by weight, about 2.5% to about 20% by weight, about 2.5% to about 25% by weight, about 5% to about 10% by weight, about 5% to about 15% by weight, about 5% to about 20% by weight, about 5% to about 25% by weight, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 70%,
  • a pharmaceutical composition disclosed herein may comprises one or more bile acids.
  • the primary purpose of bile acids are to enhance solubility of a therapeutic compound disclosed herein within the glycerolipid admixture, to enhance absorption of a therapeutic compound disclosed herein thereby improving the pharmacokinetics of the compound, and/or to improve availability and facilitate selected biodistribution of a therapeutic compound disclosed herein thereby improving the pharmacodynamics of the compound.
  • a bile acid disclosed herein improves the solubility of a therapeutic compound disclosed herein within one or more glycerolipid and/or one or more free C14-24 fatty acids disclosed herein.
  • the improved solubility properties are achieved by the bile acids by preventing the recrystallization of a therapeutic compound during solidification when the molton pharmaceutical composition cools to room temperature (18°C to 20°C).
  • the improved pharmacokinetic properties are achieved by the bile acids by breaking apart the lipid component of a pharmaceutical composition disclosed herein via its surfactant properties into smaller lipid structures that mimic emulsion droplets, thereby facilitating the emulsification process.
  • the “emulsion droplets” recruit coliapse and create a greater surface area for which pancreatic lipase can digest the hard fat glycerolipids present there within which ultimately enhances enterocyte absorption and subsequent chylomicron formation.
  • Bile acids are involved in signaling for the initiation of chylomicron formation.
  • bile acids in the lipid formulation will maximise this signaling pathway and the production of chylomicrons.
  • the improved pharmacodynamic properties provided by bile acids are produced by increasing the availability of a therapeutic compound by increasing its content within chylomicrons prior to entering the circulatory system and subsequently facilitating the delivery of the therapeutic compound to compartments such as the brain passing across membranes such as the blood-brain barrier and the choroid plexus.
  • bile acids have a specific chemical structure, different from ordinary aliphatic surfactants, due to the presence of a large, rigid, and planar hydrophobic moiety of a steroid nucleus carrying 2-4 hydroxyl groups.
  • bile acids comprise the following basic components: (1 ) 4 rings, (2) a 5-/8-carbon side chain that ends with a carboxylic acid, and (3) a number of hydroxyl groups (whose position/number changes among the various salts).
  • the rings are ascribed the letters A, B, C, and D based on their distance from the side chain with the -COOH group, the D ring being the most distant (as well as being 1 C smaller than the other rings), as discussed below.
  • Beta hydroxyl groups face up/out, alpha groups down, and every bile acid has a 3-hydroxyl group that originates from their cholesterol precursor.
  • the chemical structure of bile salts results in this emulsification pathway being useful in accordance with the teachings of the disclosure, and accordingly, synthetic surfactants will not work.
  • bile acids include, without limitation, chenodeoxycholic acid, cholic acid, dafachronic acid, deoxycholic acid, glycocholic acid, glycohenodeoxycholic acid, lithocholic acid, taurochenodeoxycholic acid, taurocholic acid, and any stereoisomer thereof.
  • cholic acid and chenodeoxycholic acid are referred to as primary bile acids while deoxycholic acid (which is converted from cholic acid) and lithocholic acid (which is converted from chenodeoxycholic acid) are referred to as secondary bile acids.
  • Taurocholic acid and glycocholic acid (derivatives of cholic acid) and taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid) are the major bile acids that serve as the basis for the bile salts found in bile.
  • a bile acid present in a pharmaceutical composition disclosed herein there is a direct correlation between the amount of a bile acid present in a pharmaceutical composition disclosed herein and the improved properties observed. As such, the more bile acid present in a pharmaceutical composition disclosed herein the greater the improvement in solubility, absorption, and availability of the therapeutic composition.
  • the upper limit of bile acid including in a pharmaceutical composition disclosed herein is not limited to the solution point of a bile acid.
  • a pharmaceutical composition disclosed herein can include supersaturating amounts of a bile acid. As such, the upper limit of bile acid that can be included in a pharmaceutical composition disclosed herein is its critical micellar concentration (CMC).
  • an additional advantage of supersaturating amounts of a bile acid is the presence of the resulting nanoparticle formation of crystalline bile acid in a pharmaceutical composition disclosed herein.
  • bile acid nanoparticles can serve as a reservoir that upon exposure to the alkaline environment of the small intestine dissolve and form bile salts which in turn further enhances the emulsification process of the pharmaceutical composition disclosed herein.
  • the amount of a bile acid useful in a pharmaceutical composition disclosed herein is an amount below its CMC. In some embodiments, the amount of a bile acid useful in a pharmaceutical composition disclosed herein is an amount below its CMC and one that is supersaturating.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more bile acids in an amount of, e.g., about 0.1% by weight, about 0.5% by weight, about 1.0% by weight, about 1.0% by weight, about 1.5% by weight, about 2.0% by weight, about 2.5% by weight, about 3.0% by weight, about 3.5% by weight, about 4.0% by weight, about 4.5% by weight, about 5.0% by weight, about 5.5% by weight, about 6.0% by weight, about 6.5% by weight, about 7.0% by weight, about 7.5% by weight, about 8.0% by weight, about 8.5% by weight, about 9.0% by weight, about 9.5% by weight, or about 10.0% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more bile acids in an amount of, e.g., at least 0.1% by weight, at least 0.5% by weight, at least 1.0% by weight, at least 1.5% by weight, at least 2.0% by weight, at least 2.5% by weight, at least 3.0% by weight, at least 3.5% by weight, at least 4.0% by weight, at least 4.5% by weight, at least 5.0% by weight, at least 5.5% by weight, at least 6.0% by weight, at least 6.5% by weight, at least 7.0% by weight, at least 7.5% by weight, at least 8.0% by weight, at least 8.5% by weight, at least 9.0% by weight, at least 9.5% by weight, or at least 10.0% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more bile acids in an amount of, e.g., at most 0.1% by weight, at most 0.5% by weight, at most 1.0% by weight, at most 1.5% by weight, at most 2.0% by weight, at most 2.5% by weight, at most 3.0% by weight, at most 3.5% by weight, at most 4.0% by weight, at most 4.5% by weight, at most 5.0% by weight, at most 5.5% by weight, at most 6.0% by weight, at most 6.5% by weight, at most 7.0% by weight, at most 7.5% by weight, at most 8.0% by weight, at most 8.5% by weight, at most 9.0% by weight, at most 9.5% by weight, or at most 10.0% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more bile acids in an amount of, e.g., about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1 % to about 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, about 0.5% to about 5.0%, about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 5.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more bile acids in a concentration of, e.g., at most 0.01 mM, at most 0.025 mM, at most 0.05 mM, at most 0.075 mM, at most 0.1 mM, at most 0.25 mM, at most 0.5 mM, at most 0.75 mM, at most 1 mM, or at most 5 mM.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more bile acids in a concentration of, e.g., about 0.01 mM to about 0.05 mM, about 0.01 mM to about 0.1 mM, about 0.01 mM to about 0.5 mM, about 0.01 mM to about 1 mM, about 0.01 mM to about 5 mM, about 0.05 mM to about 0.1 mM, about 0.05 mM to about 0.5 mM, about 0.05 mM to about 1 mM, about 0.05 mM to about 5 mM, about 0.1 mM to about 0.5 mM, about 0.1 mM to about 1 mM, about 0.1 mM to about 5 mM, or about 1 mM to about 5 mM.
  • a pharmaceutical composition disclosed herein may comprises one or more free C14-24 fatty acids.
  • a fatty acid comprises a carboxylic acid with a long unbranched hydrocarbon chain which may be either saturated or unsaturated and are hydrophobic molecules having an HUB of less than 4.
  • the primary purpose of free C14-24 fatty acids are to enhance solubility of a therapeutic compound disclosed herein within the glycerolipid admixture and to enhance absorption of a therapeutic compound disclosed herein thereby improving the pharmacokinetics of the compound.
  • the improved solubility properties are achieved by the free C14-24 fatty acids due to their properties of being a solvent that facilitates dissolvement of a therapeutic compound disclosed herein.
  • the improved absorption properties are achieved by the free C14-24 fatty acids by facilitating and increasing the formation of micelles by breaking up larger emulsion droplets, thereby mimicking the lipid digestion products of triglycerides, namely free fatty acids.
  • a C14-24 fatty acid disclosed herein increases the uptake of micelles comprising one or more therapeutic compounds into enterocytes.
  • a free C14-24 fatty acids disclosed herein improves the solubility of a bile salt disclosed herein.
  • pharmaceutical composition disclosed herein may include one or more free C14-24 fatty acids comprising, or consisting essentially of or consisting of unsaturated free C14-C16 fatty acids, unsaturated free C14-C18 fatty acids, unsaturated free C14-C20 fatty acids, unsaturated free C14-C22 fatty acids, unsaturated free C14-C24 fatty acids, unsaturated free CIB-CIS fatty acids, unsaturated free C16-C20 fatty acids, unsaturated free C16-C22 fatty acids, unsaturated free C16-C24 fatty acids, unsaturated free C18- C20 fatty acids, unsaturated free C18-C22 fatty acids, unsaturated free C18-C24 fatty acids, unsaturated free C20-C22 fatty acids, or unsaturated free C22-C24 fatty acids.
  • pharmaceutical composition disclosed herein may include one or more free C14-24 fatty acids comprising, or consisting essentially of or consisting of co-3 unsaturated free C18-C22 fatty acids, co-5 unsaturated free C18-C22 fatty acids, co-6 unsaturated free C18-C22 fatty acids, co-7 unsaturated free C18-C22 fatty acids, co-9 unsaturated free C18-C22 fatty acids, co-10 unsaturated free C18-C22 fatty acids, co— 11 unsaturated free C18-C22 fatty acids, or co-12 unsaturated free C18-C22 fatty acids.
  • composition disclosed herein may include one or more free
  • C14-24 fatty acids comprising, or consisting essentially of or consisting of saturated free C14-C16 fatty acids, saturated free C14-C18 fatty acids, saturated free C14-C20 fatty acids, saturated free C14-C22 fatty acids, saturated free C14-C24 fatty acids, saturated free CIB-CIB fatty acids, saturated free C16-C20 fatty acids, saturated free C16-C22 fatty acids, saturated free C16-C24 fatty acids, saturated free C18-C20 fatty acids, saturated free C18-C22 fatty acids, saturated free C18-C24 fatty acids, saturated free C20-C22 fatty acids, or saturated free C22-C24 fatty acids.
  • a pharmaceutical composition disclosed herein may include one or more free C14-24 fatty acids comprising, or consisting essentially of or consisting of a mixture of saturated and unsaturated free C14-C16 fatty acids, a mixture of saturated and unsaturated free C14-C18 fatty acids, a mixture of saturated and unsaturated free C14-C20 fatty acids, a mixture of saturated and unsaturated free C14-C22 fatty acids, a mixture of saturated and unsaturated free C14-C24 fatty acids, a mixture of saturated and unsaturated free CIB-CIS fatty acids, a mixture of saturated and unsaturated free C16-C20 fatty acids, a mixture of saturated and unsaturated free C16-C22 fatty acids, a mixture of saturated and unsaturated free C16-C24 fatty acids, a mixture of saturated and unsaturated free C18-C20 fatty acids, a mixture of saturated and unsaturated free C18-C22 fatty acids, a mixture of saturated and unsaturated free C18-
  • Non-limiting examples of a free C14-24 fatty acid include palmitic acid (hexadecenoic aicd), palmitolinolenic acid, palmitidonic acid, palmitovaccenic acid, palmitoleic acid, sapienic acid, 4- Hexadecenoic acid, stearic acid (octadecenoic acid), a-linolenic acid, stearidonic acid, a-eleostearic acid, p-eleostearic acid, pumicic acid, 7,10,13-octadecatrienoic acid, 12-octadecenoic acid, linoleic acid, linolelaidic acid, y-linolenic acid, calendic acid, pinolenic acid, vaccinic acid, ruminic acid, oleic acid, elaidic acid, petroselinic acid, arachidic acid (eicosanoic acid), dihomo-a-l
  • the amount of a free C14-24 fatty acid useful in a pharmaceutical composition disclosed herein is an amount that does not adversely affect the pharmacokinetics of a therapeutic compound it is being formulated with.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acids in an amount of, e.g., about 1% by weight, about 2.5% by weight, about 5% by weight, about 7.5% by weight, about 10 % by weight, about 12.5% by weight, about 15 % by weight, about 17.5% by weight, about 20% by weight, about 22.5% by weight, about 25% by weight, about 35% by weight, about 30% by weight, about 40% by weight, about 50% by weight, about 60% by weight, about 70% by weight, or about 75% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acids in an amount of, e.g., at least 1% by weight, at least 2.5% by weight, at least 5% by weight, at least 7.5% by weight, at least 10 % by weight, at least 12.5% by weight, at least 15 % by weight, at least 17.5% by weight, at least 20% by weight, at least 22.5% by weight, at least 25% by weight, at least 30% by weight, at least 35% by weight, at least 40% by weight, at least 50% by weight, at least 60% by weight, at least 70% by weight, or at least 75% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acids in an amount of, e.g., at most 1% by weight, at most 2.5% by weight, at most 5% by weight, at most 7.5% by weight, at most 10 % by weight, at most 12.5% by weight, at most 15 % by weight, at most 17.5% by weight, at most 20% by weight, at most 22.5% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 50% by weight, at most 60% by weight, at most 70% by weight, or at most 75% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acids in an amount of, e.g., about 1% to about 2.5% by weight, about 1% to about 5% by weight, about 1% to about 10% by weight, about 1% to about 15% by weight, about 1% to about 20% by weight, about 1% to about 25% by weight, about 2.5% to about 5% by weight, about 2.5% to about 10% by weight, about 2.5% to about 15% by weight, about 2.5% to about 20% by weight, about 2.5% to about 25% by weight, about 2.5% to about 30% by weight, about 5% to about 10% by weight, about 5% to about 15% by weight, about 5% to about 20% by weight, about 5% to about 25% by weight, about 5% to about 30% by weight, about 10% to about 15% by weight, about 10% to about 20% by weight, about 10% to about 25% by weight, about 10% to about 30% by weight, about 10% to about 40% by weight, about 10% to about 45% by weight,
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acids in a concentration of, e.g., at most 0.01 mM, at most 0.025 mM, at most 0.05 mM, at most 0.075 mM, at most 0.1 mM, at most 0.25 mM, at most 0.5 mM, at most 0.75 mM, at most 1 mM, at most 1.25 mM, at most 1.5 mM, at most 1.75 mM, or at most 2 mM.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acids in a concentration of, e.g., about 0.01 mM to about 0.05 mM, about 0.01 mM to about 0.1 mM, about 0.01 mM to about 0.5 mM, about 0.01 mM to about 1 mM, about 0.01 mM to about 1.25 mM, about 0.01 mM to about 1.5 mM, about 0.01 mM to about 1.75 mM, about 0.01 mM to about 2 mM, about 0.05 mM to about 0.1 mM, about 0.05 mM to about 0.5 mM, about 0.05 mM to about 1 mM, about 0.05 mM to about 1.25 mM, about 0.05 mM to about 1.5 mM, about 0.05 mM to about 1.75 mM, about 0.05 mM to about 2 mM, about 0.05 mM to about
  • a pharmaceutical composition disclosed herein may comprises one or more phospholipids.
  • phospholipids disclosed herein to break apart the lipid component of a pharmaceutical composition disclosed herein via its surfactant properties into smaller lipid structures that mimic emulsion droplets, thereby facilitating the emulsification process.
  • the “emulsion droplets” recruit coliapse and create a greater surface area for which pancreatic lipase can digest the hard fat glycerolipids present therewithin.
  • phospholipids disclosed herein along with free fatty acid surfactants disclosed herein, facilitate formation of micelles by associating with the lipid digestion products of triglycerides, and then enhancing association of the triglyceride digestion products with fatty acid transporters, thereby enhancing absorption lipid molecules and the associated therapeutic compound into enterocytes.
  • the structure of the phospholipid generally comprises a hydrophobic tail of one or more fatty acids and a hydrophilic head containing phosphoric acid functional group and is amphipathic in nature and having an HLB of greater than 12.
  • Phospholipids include, without limitation, phosphoglycerides and phosphosphingolipids.
  • Phosphoglycerides have a general structure comprising a glycerol backbone with two fatty acids esterified to the first and second hydroxyl groups of glycerol and a phosphoric acid group esterified to the third hydroxyl group of glycerol.
  • An alcohol group is esterified to the phosphoric acid group of a phosphoglyceride.
  • Phosphoglycerides always have two fatty acids usually with one fatty acid being saturated and the other being unsaturated. Phosphoglycerides are generally typed according to the particular alcohol group present on the phosphortic acid group, such as, e.g., ethanolamine, choline, serine or inositol.
  • Non-limiting examples of phosphoglycerides include a phosphatidic acid (phosphatidate) (PA), a phosphatidylethanolamine (PE), a phosphatidylcholine (PC), a phosphatidylserine (PS), a cardiolipin, and a phosphoinositide including phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2), and phosphatidylinositol triphosphate (PIP3).
  • PA phosphatidic acid
  • PE phosphatidylethanolamine
  • PC phosphatidylcholine
  • PS a phosphatidylserine
  • a cardiolipin and a phosphoinositide including phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), phosphatidyli
  • phosphosphingolipids Although structurally different, phosphosphingolipids also have a polar head and two nonpolar tails. Phosphosphingolipids have a general structure comprising a long-chain amino alcohol sphingosine backbone with a fatty acid forming an amide linkage to the amino group of to the sphingosine backbone and a phosphoric acid group esterified to the hydroxyl group of the sphingosine backbone.
  • Non-limiting examples of phosphosphingolipids include a ceramide phosphorylethanolamine (Cer-PE), and ceramide phosphorylcholine (Cer-PC), and ceramide phosphorylglycerol (Cer-PG).
  • a phospholipid in addition to its amphipathic nature, can be a zwitterionic phospholipids.
  • a zwitterionic phospholipid is a fully ionized molecule that contains an equal number of positively charged and negatively charged functional groups and is electrically neutral.
  • Non-limiting examples of a zwitterionic phospholipid include phosphatidylethanolamine (PE), phosphatidylcholine (PC), ceramide phosphorylethanolamine (Cer-PE), and ceramide phosphorylcholine (Cer-PC).
  • Phospholipids disclosed herein include lecthins.
  • Lecthins are amphiphilic mixtures of glycerophospholipids.
  • a lecthin comprises a mixture of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and phosphatidic acid.
  • a lecthin comprises 19% to 21% phosphatidylcholine, 8% to 20% phosphatidylethanolamine, 20% to 21% phosphatidylinositol, and 5% to 11% phospholipids comprising phosphatidylserine, and phosphatidic acid.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more phospholipids in an amount of, e.g., about 1.0% by weight, about 1.5% by weight, about 2.0% by weight, about 2.5% by weight, about 3.0% by weight, about 3.5% by weight, about 4.0% by weight, about 4.5% by weight, about 5.0% by weight, about 5.5% by weight, about 6.0% by weight, about 6.5% by weight, about 7.0% by weight, about 7.5% by weight, about 8.0% by weight, about 8.5% by weight, about 9.0% by weight, about 9.5% by weight, or about 10.0% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more phospholipids in an amount of, e.g., at least 1.0% by weight, at least 1.5% by weight, at least 2.0% by weight, at least 2.5% by weight, at least 3.0% by weight, at least 3.5% by weight, at least 4.0% by weight, at least 4.5% by weight, at least 5.0% by weight, at least 5.5% by weight, at least 6.0% by weight, at least 6.5% by weight, at least 7.0% by weight, at least 7.5% by weight, at least 8.0% by weight, at least 8.5% by weight, at least 9.0% by weight, at least 9.5% by weight, or at least 10.0% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more phospholipids in an amount of, e.g., at most 1.0% by weight, at most 1.5% by weight, at most 2.0% by weight, at most 2.5% by weight, at most 3.0% by weight, at most 3.5% by weight, at most 4.0% by weight, at most 4.5% by weight, at most 5.0% by weight, at most 5.5% by weight, at most 6.0% by weight, at most 6.5% by weight, at most 7.0% by weight, at most 7.5% by weight, at most 8.0% by weight, at most 8.5% by weight, at most 9.0% by weight, at most 9.5% by weight, or at most 10.0% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more phospholipids in an amount of, e.g., about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%,
  • a pharmaceutical composition disclosed herein may comprises one or more free C14-24 fatty acid surfactants.
  • a fatty acid surfactant comprises a carboxylic acid with a long unbranched hydrocarbon chain which may be either saturated or unsaturated associated with an alkali metal or other metal ion and are hydrophobic molecules amphipathic molecules having a HLB of greater than 12.
  • the primary purpose of the one or more free C14-24 fatty acid surfactants are to enhance solubility of a therapeutic compound disclosed herein with the glycerolipid admixture and to enhance absorption of a therapeutic compound disclosed herein thereby improving the pharmacokinetics of the compound.
  • the improved solubility properties are achieved by the one or more free C14-24 fatty acid surfactants through the interaction of its carboxylic acid functional group with sodium ions present on a therapeutic compound which neutralizes the charge and facilitating the compounds interaction with the hydrophobic glycolipid admixture.
  • the amount of the one or more free C14-24 fatty acid surfactants to a pharmaceutical composition disclosed herein is calculated to be stoichiometric at a minimum or supra-stoichiometric to ensure enough moles of the one or more free C14-24 fatty acid surfactants are present to displace the salt from the therapeutic compound and have the salt replaced by the fatty acid as a counterion which forms solubilized therapeutic compound in the lipid matrix.
  • the fatty acid surfactant also acts as a solubilizer of therapeutic compound in the composition, and is not acting as a counter-ion, so it can be in sub- or supra-stoichiometric concentrations.
  • the improved absorption properties are achieved by the free C14-24 fatty acid surfactants by facilitating and increasing the formation of mixed micelles by breaking up larger emulsion droplets, thereby mimicking the lipid digestion products of triglycerides, namely free fatty acids.
  • a C14-24 fatty acid surfactant disclosed herein increases the uptake of micelles comprising one or more therapeutic compounds into enterocytes.
  • a free C14-24 fatty acid surfactant disclosed herein is a free C14-24 fatty acid that is associated with an alkali metal, such as, e.g., lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), or alkaline earth metal, such as, e.g., beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).
  • an alkali metal such as, e.g., lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr)
  • alkaline earth metal such as, e.g., beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).
  • pharmaceutical composition disclosed herein may include one or more free C14-24 fatty acid surfactants comprising, or consisting essentially of or consisting of unsaturated free C14-C16 fatty acid surfactants, unsaturated free C14-C18 fatty acid surfactants, unsaturated free C14-C20 fatty acid surfactants, unsaturated free C14-C22 fatty acid surfactants, unsaturated free C14-C24 fatty acid surfactants, unsaturated free CIB-CIB fatty acid surfactants, unsaturated free C16-C20 fatty acid surfactants, unsaturated free C16-C22 fatty acid surfactants, unsaturated free C16-C24 fatty acid surfactants, unsaturated free C18-C20 fatty acid surfactants, unsaturated free C18-C22 fatty acid surfactants, unsaturated free C18-C24 fatty acid surfactants, unsaturated free C20-C22 fatty acid surfactants, unsaturated free C18-C24 fatty acid
  • pharmaceutical composition disclosed herein may include one or more free C14-24 fatty acid surfactants comprising, or consisting essentially of or consisting of co-3 unsaturated free C18-C22 fatty acid surfactants, co-5 unsaturated free C18-C22 fatty acid surfactants, co-6 unsaturated free C18-C22 fatty acid surfactants, co-7 unsaturated free C18-C22 fatty acid surfactants, co-9 unsaturated free C18-C22 fatty acid surfactants, co-10 unsaturated free C18-C22 fatty acid surfactants, co— 11 unsaturated free C18-C22 fatty acid surfactants, or co-12 unsaturated free C18-C22 fatty acid surfactants.
  • free C14-24 fatty acid surfactants comprising, or consisting essentially of or consisting of co-3 unsaturated free C18-C22 fatty acid surfactants, co-5 unsaturated free C18-C22 fatty acid surfactants, co-6 unsaturated free C18-C22 fatty acid
  • pharmaceutical composition disclosed herein may include one or more free C14-24 fatty acid surfactants comprising, or consisting essentially of or consisting of saturated free C14-C16 fatty acid surfactants, saturated free C14-C18 fatty acid surfactants, saturated free C14-C20 fatty acid surfactants, saturated free C14-C22 fatty acid surfactants, saturated free C14-C24 fatty acid surfactants, saturated free CIB-CIS fatty acid surfactants, saturated free C16-C20 fatty acid surfactants, saturated free C16-C22 fatty acid surfactants, saturated free C16-C24 fatty acid surfactants, saturated free C18-C20 fatty acid surfactants, saturated free C18-C22 fatty acid surfactants, saturated free C18-C24 fatty acid surfactants, saturated free C20-C22 fatty acid surfactants, or saturated free C22-C24 fatty acid surfactants.
  • a pharmaceutical composition disclosed herein may include one or more free C14-24 fatty acid surfactants comprising, or consisting essentially of or consisting of a mixture of saturated and unsaturated free C14-C16 fatty acid surfactants, a mixture of saturated and unsaturated free C14-C18 fatty acid surfactants, a mixture of saturated and unsaturated free C14-C20 fatty acid surfactants, a mixture of saturated and unsaturated free C14-C22 fatty acid surfactants, a mixture of saturated and unsaturated free C14-C24 fatty acid surfactants, a mixture of saturated and unsaturated free C16-C18 fatty acid surfactants, a mixture of saturated and unsaturated free C16-C20 fatty acid surfactants, a mixture of saturated and unsaturated free C16-C22 fatty acid surfactants, a mixture of saturated and unsaturated free C16-C24 fatty acid surfactants, a mixture of saturated and unsaturated free C18-
  • Non-limiting examples of a free C14-24 fatty acid surfactant include sodium palmitate (hexadecanoate), sodium palmitolinolenate, sodium palmitidonate, sodium palmitovaccenate, sodium palmitoleate, sodium sapienate, sodium 4-Hexadecenoate, sodium stearate (octadecenoate), sodium a- linolenate, sodium stearidonate, sodium a-eleostearate, sodium p-eleostearate, sodium pumicate, sodium 7,10,13-octadecatrienoate, sodium 12-octadecenoate, sodium linoleate, sodium linolelaidate.
  • the lower limit of one or more free C14-24 fatty acid surfactants that can be included in a pharmaceutical composition disclosed herein is an amount sufficient to solubilize a therapeutic compound and confer its improved absorption properties.
  • the upper limit of one or more free C14-24 fatty acid surfactants that can be included in a pharmaceutical composition disclosed herein is its micellar concentration (CMC).
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acid surfactants in an amount of, e.g., about 0.1% by weight, about 0.5% by weight, about 1.0% by weight, about 1.0% by weight, about 1.5% by weight, about 2.0% by weight, about 2.5% by weight, about 3.0% by weight, about 3.5% by weight, about 4.0% by weight, about 4.5% by weight, about 5.0% by weight, about 5.5% by weight, about 6.0% by weight, about 6.5% by weight, about 7.0% by weight, about 7.5% by weight, about 8.0% by weight, about 8.5% by weight, about 9.0% by weight, about 9.5% by weight, or about 10.0% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acid surfactants in an amount of, e.g., at least 0.5% by weight, at least 1.0% by weight, at least 1.5% by weight, at least 2.0% by weight, at least
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acid surfactants in an amount of, e.g., at most 0.1% by weight, at most 0.5% by weight, at most 1.0% by weight, at most 1.5% by weight, at most 2.0% by weight, at most 2.5% by weight, at most 3.0% by weight, at most 3.5% by weight, at most 4.0% by weight, at most 4.5% by weight, at most 5.0% by weight, at most 5.5% by weight, at most 6.0% by weight, at most 6.5% by weight, at most 7.0% by weight, at most 7.5% by weight, at most 8.0% by weight, at most 8.5% by weight, at most 9.0% by weight, at most 9.5% by weight, or at most 10.0% by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acid surfactants in an amount of, e.g., about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1% to about 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, about 0.5% to about 5.0%, about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 3.0%, about 1.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acid surfactants in a concentration of, e.g., at most 5 M, at most 10 M, at most 15 pM, at most 20 pM, at most 25 pM, at most pM, or at most 35 pM.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of one or more free C14-24 fatty acid surfactants in a concentration of, e.g., about 1 pM to about 5 pM, about 1 pM to about 10 pM, about 1 pM to about 15 pM, about 1 pM to about 20 pM, about 1 pM to about 25 pM, about 1 pM to about 30 pM, about 1 pM to about 35 pM, about 5 pM to about 10 pM, about 5 pM to about 15 pM, about 5 pM to about 20 pM, about 5 pM to about 25 pM, about 5 pM to about 30 pM, about 5 pM to about 35 pM, about 10 pM to about 15 pM, about 10 pM to about 20 pM, about 10 pM to about 25 pM, about 10 pM to about 30 pM, about 5 pM
  • a pharmaceutical composition disclosed herein may include a curcumin.
  • Curcumin is a pigment of phenolic nature extracted from Curcuma longa. Although a pharmacologically bioactive molecule, curcumin is able to facilitate gall bladder contraction, making this compound useful as a digestion enhancer disclosed herein. Gall bladder contraction is an important process in the absorption of fat and thus provide an important benefit increase the formation of mixed micelles by breaking up larger emulsion droplets, thereby increasing the uptake of micelles comprising one or more therapeutic compounds into enterocytes. While a highly insoluble compound, curcumin is soluble using a formulation disclosed herein.
  • the amount of a curcumin useful in a pharmaceutical composition disclosed herein is a therapeutically effective amount or an amount effective in facilitating gall bladder contraction.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of curcumin in an amount of, e.g., about 0.1%, about 0.5%, about 1% by weight, about 1.5% by weight, about 2% by weight, about 2.5% by weight, about 3% by weight, about 4% by weight, about 5% by weight, about 7.5% by weight, or about 10 % by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of curcumin in an amount of, e.g., at least 0.1%, at least 0.5%, at least 1% by weight, at least 1.5% by weight, at least 2% by weight, at least 2.5% by weight, at least 3% by weight, at least 4% by weight, at least 5% by weight, at least 7.5% by weight, or at least 10 % by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of curcumin in an amount of, e.g., at most 0.1%, at most 0.5%, at most 1% by weight, at most 1.5% by weight, at most 2% by weight, at most 1% by weight, at most 1 .5% by weight, at most 2% by weight, at most 2.5% by weight, at most 3% by weight, at most 4% by weight, at most 5% by weight, at most 7.5% by weight, or at most 10 % by weight.
  • a pharmaceutical composition disclosed herein may comprising or consisting essentially of or consisting of curcumin in an amount of, e.g., about 0.1% to about 1% by weight, about 0.1% to about 1.5% by weight, about 0.1% to about 2% by weight, about 0.1% to about 2.5% by weight, about 0.1% to about 5% by weight, about 0.1% to about 7.5% by weight, about 0.1% to about 10% by weight, about 0.5% to about 1% by weight, about 0.5% to about 1.5% by weight, about 0.5% to about 2% by weight, about 0.5% to about 2.5% by weight, about 0.5% to about 5% by weight, about 0.5% to about 7.5% by weight, about 0.5% to about 10% by weight, about 1% to about 1.5% by weight, about 1% to about 2% by weight, about 1% to about 2.5% by weight, about 1% to about 5% by weight, about 1% to about 7.5% by weight, or about 1% to about 10% by weight.
  • a glycol polymer may include one or more glycol polymers.
  • a pharmaceutical composition disclosed herein may comprise a stabilizing agent in an amount sufficient to stabilize the free acid or base present in a therapeutic compound disclosed herein.
  • a pharmaceutical composition disclosed herein may comprise a stabilizing agent in an amount of, e.g., less than about 40% by weight, less than about 35% by weight, less than about 30% by weight, less than about 25% by weight, less than about 20% by weight, less than about 19% by weight, less than about 18% by weight, less than about 17% by weight, less than about 16% by weight, less than about 15% by weight, less than about 14% by weight, less than about 13% by weight, less than about 12% by weight, less than about 11% by weight, less than about 10% by weight, less than about 9% by weight, less than about 8% by weight, less than about 7% by weight, less than about 6% by weight, less than about 5% by weight, less than about 4% by weight, less than about 3% by weight, less than about 2% by weight, or less than about 1%.
  • a pharmaceutical composition disclosed herein may comprise a stabilizing agent in an amount of, e.g., about 1% to about 5% by weight, about 1% to about 7% by weight, about 1% to about 10% by weight, about 1% to about 12% by weight, about 1 % to about 15% by weight, about 1% to about 18% by weight, about 1% to about 20% by weight, about 2% to about 5% by weight, about 2% to about 7% by weight, about 2% to about 10% by weight, about 2% to about 12% by weight, about 2% to about 15% by weight, about 2% to about 18% by weight, about 2% to about 20% by weight, about 3% to about 5% by weight, about 3% to about 7% by weight, about 3% to about 10% by weight, about 3% to about 12% by weight, about 3% to about 15% by weight, about 3% to about 18% by weight, about 3% to about 20% by weight, about 4% to about 5% by weight, about 4% to about 7% by weight, about 4% to about 5%
  • a stability agent as disclosed herein is not a solvent as it is used in an amount that does not result in substantial dissolving of a solute. As such, the amount stability agent used in a solid solution composition disclosed herein results in no more than 85% dissolution of a therapeutic compound disclosed herein. In aspects of this embodiment, he amount stability agent used in a solid solution composition disclosed herein results in.
  • a glycol polymer may comprise a pharmaceutically-acceptable PEG polymer.
  • PEG polymers also known as polyethylene oxide (PEG) polymers or polyoxyethylene (POE) polymers, are prepared by polymerization of ethylene oxide and are commercially available over a wide range of molecular weights from 100 g/mol to 10,000,000 g/mol.
  • PEG polymers with a low molecular mass are liquids or low-melting solids, whereas PEG polymers of a higher molecular mass are solids.
  • a PEG polymer used as a stability agent is a liquid PEG polymer.
  • a PEG polymer has a molecular weight of, e.g., no more than 100 g/mol, no more than 200 g/mol, no more than 300 g/mol, no more than 400 g/mol, no more than 500 g/mol, no more than 600 g/mol, no more than 700 g/mol, no more than 800 g/mol, no more than 900 g/mol, or no more than 1000 g/mol.
  • a PEG polymer include, without limitation, PEG 100, PEG 200, PEG 300, PEG 400, PEG 500, PEG 600, PEG 700, PEG 800, PEG 900, PEG 1000, PEG 1100, PEG 1200, PEG 1300, PEG 1400, PEG 1500,
  • PEG 2500 PEG 2600, PEG 2700, PEG 2800, PEG 2900, PEG 3000, PEG 3250, PEG 3350, PEG 3500,
  • PEG 3750 PEG 4000, PEG 4250, PEG 4500, PEG 4750, PEG 5000, PEG 5500, PEG 6000, PEG 6500,
  • a glycol polymer may comprise a pharmaceutically-acceptable polypropylene glycol (PPG) polymer.
  • PPG polymers also known as polypropylene oxide (PPG) polymers or polyoxypropylene (POP) polymers, are prepared by polymerization of propylene oxide and are commercially available over a wide range of molecular weights from 100 g/mol to 10,000,000 g/mol.
  • PPG polymers with a low molecular mass are liquids or low-melting solids, whereas PPG polymers of a higher molecular mass are solids.
  • a PPG polymer used as a stability agent is a liquid PPG polymer.
  • a PPG polymer has a molecular weight of, e.g., no more than 100 g/mol, no more than 200 g/mol, no more than 300 g/mol, no more than 400 g/mol, no more than 500 g/mol, no more than 600 g/mol, no more than 700 g/mol, no more than 800 g/mol, no more than 900 g/mol, or no more than 1000 g/mol.
  • a PPG polymer include, without limitation, PPG 100, PPG 200, PPG 300, PPG 400, PPG 500, PPG 600, PPG 700, PPG 800, PPG 900, PPG 1000, PPG 1100, PPG 1200, PPG 1300, PPG 1400, PPG 1500,
  • PPG 2500 PPG 2600, PPG 2700, PPG 2800, PPG 2900, PPG 3000, PPG 3250, PPG 3350, PPG 3500,
  • PPG 3750 PPG 4000, PPG 4250, PPG 4500, PPG 4750, PPG 5000, PPG 5500, PPG 6000, PPG 6500,
  • a pharmaceutical composition disclosed herein does not include a glycol polymer. In aspects of these embodiments, a pharmaceutical composition disclosed herein does not include a PEG polymer. In other aspects of these embodiments, a pharmaceutical composition disclosed herein does not include a PGG polymer. In yet other aspects of these embodiments, a pharmaceutical composition disclosed herein does not include both a PEG polymer and a PGG polymer.
  • a substantial amount of a therapeutic compound present in a pharmaceutical composition disclosed herein is delivered to or enters a lipid digestion and/or absorption pathway.
  • about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80% about 90%, or about 95% of a therapeutic compound present in a pharmaceutical composition disclosed herein is delivered to or enters a lipid digestion and/or absorption pathway.
  • At least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80% at least 90%, or at least 95% of a therapeutic compound present in a pharmaceutical composition disclosed herein is delivered to or enters a lipid digestion and/or absorption pathway.
  • at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80% at most 90%, or at most 95% of a therapeutic compound present in a pharmaceutical composition disclosed herein is delivered to or enters a lipid digestion and/or absorption pathway.
  • an insubstantial amount of a therapeutic compound present in a pharmaceutical composition disclosed herein is absorbed by blood capillaries and enters directly into the blood.
  • at most 1%, at most 5%, at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80% at most 90%, or at most 95% of a therapeutic compound present in a pharmaceutical composition disclosed herein is absorbed by blood capillaries and enters directly into the blood.
  • the inclusion of one or more digestion enhancers to one or more therapeutic compounds to a pharmaceutical composition disclosed herein is applicable to any therapeutic compound administered by a route of administration where uptake of the compound is achieved by absorption through the gastrointestinal tract, such as, e.g., oral delivery.
  • formulation of a pharmaceutical composition disclosed herein is dependent on the solubility of a therapeutic compound in the one or more glycerolipid used in formulating the pharmaceutical composition.
  • formulation of any one particular therapeutic compound disclosed herein is achieved by the process described below which produces pharmaceutical compositions where one or more therapeutic compounds remain stably incorporated in the glycerolipid mixture.
  • a selected therapeutic compound can be formulated using 1 ) glycerolipids including at least one liquid fat (glycerolipid that is liquid at 18°C) and at least one hard fat (glycerolipid that is solid at 18°C) and 2) one or more digestion enhancers.
  • the one or more liquid and hard fats are first heated and the one or more digestion enhancers are solubilized in the glycerolipid admixture. Upon completion of solubility of the digestion enhancers, and if appropriate, the temperature of the admixture can be adjusted anda selected therapeutic compound is then dissolved in this heated admixture to incorporate the compound.
  • the one or more liquid fats are first heated and the one or more digestion enhancers are solubilized in the liquid fats. Upon completion of solubility of the digestion enhancers, and if appropriate, the temperature of the admixture can be adjusted and a selected therapeutic compound is then dissolved in this heated admixture to incorporate the compound. Upon complete dissolution of the therapeutic compound, one or more hard fats are then added to this heated admixture. In some embodiments, one or more digestion enhancers are first heated and a selected therapeutic compound is then dissolved to this heated admixture to incorporate the compound.
  • the temperature of the admixture can be adjusted and one or more liquid fats are then added and incorporated into this admixture.
  • one or more hard fats are then added and incorporated into this admixture.
  • the initial heating step in all procedures is performed at a temperature sufficient to dissolve the one or more digestion enhancers and selected therapeutic compound and can be empirically determined based on the melting point of the selected components. Generally, this temperature range is about 60°C to about 170°C.
  • any subsequent adjustment to the heat when one or more liquid fats and/or one or more heart fats are being added to the admixture is performed at a temperature sufficient to melt the hard fats and can be empirically determined based on the melting point of the hard fat used in the formulation. Generally, this temperature range is about 40°C to about 60°C.
  • the pharmaceutical composition can be optionally stability tested by reheating the composition to a temperature sufficient to cause it to melt.
  • the reheating step is performed at a temperature sufficient to melt the glycerolipid components and can be empirically determined based on the melting point of the hard fat used in the formulation. Generally, this temperature range is 40°C to 50°C.
  • the selection of the one or more digestion enhancers is generally not a critical component in this process, as a bile acid, free fatty acid, phospholipid, or free fatty acid surfactant can all be used in any combination to achieve a pharmaceutical composition disclosed herein.
  • the preparative methods all include a complete dissolution phase that upon cooling nano-crystallization of some components occurs and this is described in the XRPD spectra.
  • aspects of the present specification disclose, in part, a method of treating an individual with a disease or disorder.
  • the method comprises the step of administering to an individual in need thereof a pharmaceutical composition disclosed herein, wherein administration reduces a symptom associated with the disease or disorder, thereby treating the individual.
  • aspects of the present specification disclose, in part, a pharmaceutical composition disclosed herein for use in the treatment of a disease or disorder.
  • aspects of the present specification disclose, in part, use of a pharmaceutical composition disclosed herein for the treatment of a disease or disorder.
  • aspects of the present specification disclose, in part, use of a pharmaceutical composition disclosed herein in the manufacture of a medicament for the treatment of a disease or disorder.
  • a disease or disorder disclosed herein includes, without limitation, a neoplasm, a cancer, an inflammation, an autoimmune disorder, an idiopathic pulmonary fibrosis, and a renal disease or disorder.
  • a pharmaceutical composition disclosed herein relies on the digestive process of the gastrointestinal tract, oral administration is the preferred route of administration.
  • aspects of the present specification disclose, in part, treating an individual suffering from a disease or disorder.
  • the term “treating,” refers to reducing or eliminating in an individual a clinical symptom of a disease or disorder; or delaying or preventing in an individual the onset of a clinical symptom of a disease or disorder.
  • the term “treating” can mean reducing a symptom of a condition characterized by a disease or disorder by, e.g., at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% at least 95%, or at least 100%.
  • the actual symptoms associated with a disease or disorder are well known and can be determined by a person of ordinary skill in the art by taking into account factors, including, without limitation, the location of the disease or disorder, the cause of the disease or disorder, the severity of the disease or disorder, and/or the tissue or organ affected by the disease or disorder. Those of skill in the art will know the appropriate symptoms or indicators associated with a specific type of disease or disorder and will know how to determine if an individual is a candidate for treatment as disclosed herein.
  • Neoplasms can be divided into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior.
  • a neoplasm can be benign, potentially malignant, or malignant (/.e., cancer).
  • a benign neoplasm include uterine fibroids, osteophytes and melanocytic nevi (skin moles).
  • Potentially-malignant neoplasms are localized, do not invade or destroy surrounding tissue but have the potential to transform into a malignant neoplasm.
  • neoplasms include carcinoma in situ. Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may metastasis and, if untreated or unresponsive to treatment, will generally prove fatal. Secondary neoplasm refers to any of a class of cancer that is either a metastatic offshoot of a primary tumor, or an apparently unrelated tumor that increases in frequency following certain cancer treatments such as chemotherapy or radiotherapy. Rarely there can be a metastatic neoplasm with no known site of the primary cancer and this is classed as a cancer of unknown primary origin. [0145] Aspects of the present specification disclose, in part, a disease or disorder that is a cancer.
  • Cancer or malignant neoplasm, is a large group of diseases involving uncontrolled growth and division of abnormal cells.
  • a cancer can be a primary cancer, the initial or original malignant neoplastic disease, or a metastatic cancer, a malignant neoplasm deriving from a primary cancer that spread or invaded to other parts of the body cause new malignant neoplasms.
  • a cancer can be a solid tumor comprising an abnormal mass of tissue that usually does not contain cysts or liquid areas, or a non-solid (blood) tumor, malignant neoplasms lacking mass.
  • Cancers are classified by the type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include carcinomas, sarcomas, lymphomas and leukemias, germ cell tumors, and blastomas.
  • a carcinoma is malignancy arising from epithelial cells, including the epithelial lining that covers the surface of internal organs and glands. This group includes many of the most common cancers and include nearly all those in the bladder, brain, breast, cervical, colon, endometrium, kidney, liver, lung, ovarian, pancreas prostate, rectum, skin, small intestine, stomach, thyroid, and uterus.
  • a sarcoma is malignancy arising from mesenchymal cells and include neoplasms derived from connective tissue such as, e.g., bone, cartilage, fat, nervous, and vascular tissue,
  • a lymphoma or leukemia is malignancy arising from hematopoietic (blood-forming) cells that leave the marrow and tend to mature in the lymph nodes (lymphoma) and blood (leukemia).
  • a germ cell tumor is malignancy arising from pluripotent cells, most often presenting in the testicle or the ovary (seminoma and dysgerminoma, respectively).
  • a blastoma is malignancy arising from immature "precursor" cells or embryonic tissue.
  • Non-limiting examples of a cancer include a basil-cell skin cancer, a bladder cancer, a brain cancer, a breast cancer, a cervical cancer, a colon cancer, an endometrial cancer, a glioblastoma, a Hodgkin's lymphoma, a non-Hodgkin's lymphoma, a kidney cancer, a leukemia, a lip cancer, a liver cancer, a lymphoma, a melanoma, a mesothelioma, a myeloma, a non-small cell lung cancer, a non-melanoma skin cancer, an oral cancer, an ovarian cancer, a pancreatic cancer, a prostate cancer, a rectal cancer, a sarcoma, a small cell lung cancer, a squamous cell skin cancer, and a thyroid cancer.
  • a cancer includes a bone or muscle cancer including, without limitation, a chondrosarcoma, an Ewing's sarcoma, a malignant fibrous histiocytoma, an osteosarcoma, a rhabdomyosarcoma, and a heart cancer.
  • a cancer includes a brain or neuronal cancer including, without limitation, an astrocytoma, a brainstem glioma, a pilocytic astrocytoma, an ependymoma, a primitive neuroectodermal tumor, a cerebellar astrocytoma, a cerebral astrocytoma, a glioblastoma, a glioma, a medulloblastoma, a neuroblastoma, an oligodendroglioma, a pineal astrocytoma, a pituitary adenoma, and hypothalamic glioma.
  • an astrocytoma a brainstem glioma, a pilocytic astrocytoma, an ependymoma, a primitive neuroectodermal tumor, a cerebellar astrocytoma, a cerebral astrocytoma, a
  • a cancer includes a breast cancer including, without limitation, a female breast cancer, an invasive cribriform carcinoma, an invasive lobular carcinoma, a medullary carcinoma, a male breast cancer, a phyllodes tumor, and a tubular carcinoma.
  • a cancer includes an endocrine cancer including, without limitation, an adrenocortical carcinoma, an islet cell carcinoma (endocrine pancreas), a merkel cell carcinoma, a multiple endocrine neoplasia syndrome, a parathyroid cancer, a pheochromocytoma, and a thyroid cancer.
  • an endocrine cancer including, without limitation, an adrenocortical carcinoma, an islet cell carcinoma (endocrine pancreas), a merkel cell carcinoma, a multiple endocrine neoplasia syndrome, a parathyroid cancer, a pheochromocytoma, and a thyroid cancer.
  • a cancer includes an eye cancer including, without limitation, a retinoblastoma and an uveal melanoma
  • a cancer includes a gastrointestinal cancer including, without limitation, an anal cancer, an appendix cancer, a cholangiocarcinoma, a colon cancer, an extrahepatic bile duct cancer, a gallbladder cancer, a gastric (stomach) cancer, a gastrointestinal carcinoid tumor, a gastrointestinal stromal tumor (GIST), a hepatocellular cancer, an islet cell cancer, a pancreatic cancer, and a rectal cancer.
  • a gastrointestinal cancer including, without limitation, an anal cancer, an appendix cancer, a cholangiocarcinoma, a colon cancer, an extrahepatic bile duct cancer, a gallbladder cancer, a gastric (stomach) cancer, a gastrointestinal carcinoid tumor, a gastrointestinal stromal tumor (GIST), a hepatocellular cancer, an islet cell cancer, a pancreatic cancer, and a rectal cancer.
  • a cancer includes a genitourinary or gynecologic cancer including, without limitation, a bladder cancer, a cervical cancer, an endometrial cancer, an extragonadal germ cell tumor, a gestational trophoblastic cancer, an ovarian cancer, an ovarian epithelial cancer (surface epithelial-stromal tumor), an ovarian germ cell cancer, a penile cancer, a renal cell carcinoma, a prostate cancer, a transitional cell cancer (renal pelvis to ureter or ureter and renal pelvis), a testicular cancer, an urethral cancer, an uterine sarcoma, a vaginal cancer, a vulvar cancer, and a Wilms tumor.
  • a bladder cancer including, without limitation, a bladder cancer, a cervical cancer, an endometrial cancer, an extragonadal germ cell tumor, a gestational trophoblastic cancer, an ovarian cancer, an ovarian epithelial cancer (surface epitheli
  • a cancer includes a head and neck cancer including, without limitation, an esophageal cancer, a head cancer, a hypopharyngeal cancer, a neck cancer, a nasopharyngeal carcinoma, an oral cancer, an oropharyngeal cancer, a paranasal sinus and nasal cavity cancer, a pharyngeal cancer, a salivary gland cancer.
  • a cancer includes a hematopoietic cancer including, without limitation, an acute biphenotypic leukemia, an acute eosinophilic leukemia, an acute lymphoblastic leukemia, an acute myeloid leukemia, an acute myeloid dendritic cell leukemia, an AIDS-related lymphoma, an anaplastic large cell lymphoma, an angioimmunoblastic T-cell lymphoma, a EB-cell prolymphocytic leukemia, a Burkitt's lymphoma, a chronic lymphocytic leukemia, a chronic myelogenous leukemia, a cutaneous T-cell lymphoma, a diffuse large B-cell lymphoma, a follicular lymphoma, a hairy cell leukemia, a hepatosplenic T-cell lymphoma, a Hodgkin's lymphoma, an intravascular large B
  • a cancer includes a skin cancer including, without limitation, a basal cell carcinoma, a dermatofibrosarcoma protuberans sarcoma, a melanoma, a Merkel cell carcinoma, a sebaceous carcinoma, a skin adnexal tumor, and a squamous cell carcinoma.
  • a cancer includes a thoracic or respiratory cancer including, without limitation, a bronchial adenoma/carcinoid, a laryngeal cancer, a mesothelioma, a non-small cell lung cancer, a pleuropulmonary blastoma, a small cell lung cancer, a thymoma, and a thymic carcinoma.
  • a cancer includes a HIV/AIDS related cancer including, without limitation, a AIDS-related cancer and a Kaposi sarcoma.
  • a cancer includes an epithelioid hemangioendothelioma (EHE), a desmoplastic small round cell tumor, and a liposarcoma.
  • EHE epithelioid hemangioendothelioma
  • desmoplastic small round cell tumor a desmoplastic small round cell tumor
  • liposarcoma a liposarcoma
  • aspects of the present specification disclose, in part, a disease or disorder that is a chronic inflammation.
  • Inflammation involves the activation of the immune system in response to harmful stimuli, such as, e.g., a pathogen, infection, irritant, or damage to cells.
  • harmful stimuli such as, e.g., a pathogen, infection, irritant, or damage to cells.
  • inflammation is a mechanism of innate immunity, as compared to adaptive immunity, which is specific for each pathogen. Inflammation can be classified as either acute or chronic.
  • acute inflammation is mediated by granulocytes
  • chronic inflammation is mediated by mononuclear cells such as monocytes and lymphocytes.
  • Acute inflammation is an initial protective response of the body to remove an injurious stimulus by maintaining tissue integrity and contributing to tissue repair. It is a part of the body’s natural defense system against injury and disease, and in the absence of acute inflammation, wounds and infections would never heal and progressive destruction of the tissue would compromise the survival of the organism.
  • the process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells, mastocytes, vascular endothelial cells, and vascular smooth muscle cells.
  • these cells undergo activation and release inflammatory mediating and sensitizing molecules, such as, e.g., pro-inflammatory cytokines, pro- inflammatory prostaglandins, leukotrienes, histamine, serotonin, neutral proteases, bradykinin and nitric oxide.
  • inflammatory molecules modulate a complex series of biological events involving cellular and acellular components of the local vascular system, the immune system, and the injured tissue site to propagate and mature the inflammatory response.
  • These events are responsible for eliciting an acute inflammatory response, typically characterized by 1) vasodilatation which increases blood flow into the tissue thereby causing erythema (redness and warmth), which may extend beyond this site (the flare response); 2) blood vessel permeability which increases plasma leakage into the tissue thereby causing edema (swelling); 3) alter the excitability of certain sensory neurons causing hypersensitivity and pain; 4) stimulate the release of inflammation inducing molecules such as, e.g., neuropeptides like substance P (SP) and calcitonin gene-related peptide (CGRP), prostaglandins, and amino acids like glutamate, from the peripheral nerve endings; and 5) increase migration of leukocytes, mainly granulocytes, from the blood vessels into the tissue.
  • Chronic inflammation may be characterized as the simultaneous destruction and healing of tissue from the inflammatory process, with the net result of provoking injury rather than mediating repair.
  • chronic inflammation is a disease.
  • an inflammatory response can occur anywhere in the body, chronic inflammation has been implicated in the pathophysiology of a wide range of seemingly unrelated disorders which underlay a large and varied group of human diseases.
  • chronic inflammation is involved in diseases as diverse as cardiovascular diseases, cancers, allergies, obesity, diabetes, digestive system diseases, degenerative diseases, auto-immune disorders, and Alzheimer's disease.
  • Chronic inflammation symptoms include, without limitation, edema, hyperemia, erythema, bruising, tenderness, stiffness, swollenness, fever, chills, stuffy nose, stuffy head, breathing problems, fluid retention, blood clots, loss of appetite, increased heart rate, formation of granulomas, fibrinous, pus, non-viscous serous fluid, or ulcer and pain.
  • the actual symptoms associated with a chronic inflammation are well known and can be determined by a person of ordinary skill in the art by taking into account factors, including, without limitation, the location of the inflammation, the cause of the inflammation, the severity of the inflammation, the tissue or organ affected, and the associated disorder.
  • granulomatous inflammation is an inflammation resulting from the formation of granulomas arising from a limited but diverse number of diseases, include, without limitation, tuberculosis, leprosy, sarcoidosis, and syphilis.
  • Purulent inflammation is an inflammation resulting in large amount of pus, which consists of neutrophils, dead cells, and fluid. Infection by pyogenic bacteria such as staphylococci is characteristic of this kind of inflammation.
  • Serous inflammation is an inflammation resulting from copious effusion of non- viscous serous fluid, commonly produced by mesothelial cells of serous membranes, but may be derived from blood plasma. Skin blisters exemplify this pattern of inflammation. Ulcerative inflammation is an inflammation resulting from the necrotic loss of tissue from the epithelial surface, exposing lower layers and forming an ulcer.
  • a chronic inflammation symptom can be associated with a large, unrelated group of disorders which underlay a variety of diseases and disorders.
  • the immune system is often involved with chronic inflammatory disorders, demonstrated in both allergic reactions and some myopathies, with many immune system disorders resulting in abnormal inflammation.
  • Non-immune diseases with etiological origins in chronic inflammatory processes include cancer, atherosclerosis, and ischaemic heart disease.
  • Non-limiting examples of disorders exhibiting chronic inflammation as a symptom include, without limitation, acne, acid reflux/heartburn, age related macular degeneration (AMD), allergy, allergic rhinitis, Alzheimer’s disease, amyotrophic lateral sclerosis, anemia, appendicitis, arteritis, arthritis, asthma, atherosclerosis, autoimmune disorders, balanitis, blepharitis, bronchiolitis, bronchitis, a bullous pemphigoid, burn, bursitis, cancer, cardiac arrest, carditis, celiac disease, cellulitis, cervicitis, cholangitis, cholecystitis, chorioamnionitis, chronic obstructive pulmonary disease (COPD), cirrhosis, colitis, congestive heart failure, conjunctivitis, cyclophosphamide-induced cystitis, cystic fibrosis, cystitis, common cold, dacryoadenitis
  • a chronic inflammation comprises a tissue inflammation.
  • Tissue inflammation is a chronic inflammation that is confined to a particular tissue or organ.
  • a tissue inflammation comprises, e.g., a skin inflammation, a muscle inflammation, a tendon inflammation, a ligament inflammation, a bone inflammation, a cartilage inflammation, a lung inflammation, a heart inflammation, a liver inflammation, a pancreatic inflammation, a kidney inflammation, a bladder inflammation, a stomach inflammation, an intestinal inflammation, a neuronal inflammation, and a brain inflammation.
  • a chronic inflammation comprises a systemic inflammation.
  • systemic inflammation is not confined to a particular tissue but in fact overwhelms the body, involving the endothelium and other organ systems.
  • sepsis is applied, with the terms bacteremia being applied specifically for bacterial sepsis and viremia specifically to viral sepsis.
  • bacteremia being applied specifically for bacterial sepsis and viremia specifically to viral sepsis.
  • Vasodilation and organ dysfunction are serious problems associated with widespread infection that may lead to septic shock and death.
  • a chronic inflammation comprises an arthritis.
  • Arthritis includes a group of conditions involving damage to the joints of the body due to the inflammation of the synovium including, without limitation osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthropathies like ankylosing spondylitis, reactive arthritis (Reiter's syndrome), psoriatic arthritis, enteropathic arthritis associated with inflammatory bowel disease, Whipple disease and Behcet disease, septic arthritis, gout (also known as gouty arthritis, crystal synovitis, metabolic arthritis), pseudogout (calcium pyrophosphate deposition disease), and Still's disease. Arthritis can affect a single joint (monoarthritis), two to four joints (oligoarthritis) or five or more joints (polyarthritis) and can be either an auto-immune disease or a non- autoimmune disease.
  • a chronic inflammation comprises an autoimmune disorder.
  • Autoimmune diseases can be broadly divided into systemic and organ-specific autoimmune disorders, depending on the principal clinico-pathologic features of each disease.
  • Systemic autoimmune diseases include, without limitation, systemic lupus erythematosus (SLE), Sjogren's syndrome, Scleroderma, rheumatoid arthritis, and polymyositis.
  • Local autoimmune diseases may be endocrinologic (Diabetes Mellitus Type 1 , Hashimoto's thyroiditis, Addison's disease etc.), dermatologic (pemphigus vulgaris), hematologic (autoimmune haemolytic anemia), neural (multiple sclerosis) or can involve virtually any circumscribed mass of body tissue.
  • endocrinologic Diabetes Mellitus Type 1 , Hashimoto's thyroiditis, Addison's disease etc.
  • dermatologic pemphigus vulgaris
  • hematologic autoimmune haemolytic anemia
  • neural multiple sclerosis
  • Types of autoimmune disorders include, without limitation, acute disseminated encephalomyelitis (ADEM), Addison's disease, an allergy or sensitivity, amyotrophic lateral sclerosis, antiphospholipid antibody syndrome (APS), arthritis, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune pancreatitis, bullous pemphigoid, celiac disease, Chagas disease, chronic obstructive pulmonary disease (COPD), diabetes mellitus type 1 (IDDM), endometriosis, fibromyalgia, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome (GBS), Hashimoto's thyroiditis, hidradenitis suppurativa, idiopathic thrombocytopenic purpura, inflammatory bowel disease, interstitial cystitis, lupus (including discoid lupus erythematosus, drug-induced lupus
  • a chronic inflammation comprises a myopathy.
  • Myopathies are caused when the immune system inappropriately attacks components of the muscle, leading to inflammation in the muscle.
  • a myopathy includes an inflammatory myopathy and an auto-immune myopathy.
  • Myopathies include, without limitation, dermatomyositis, inclusion body myositis, and polymyositis.
  • a chronic inflammation comprises a vasculitis.
  • Vasculitis is a varied group of disorders featuring inflammation of a vessel wall including lymphatic vessels and blood vessels like veins (phlebitis), arteries (arteritis) and capillaries due to leukocyte migration and resultant damage.
  • the inflammation may affect any size blood vessel, anywhere in the body. It may affect either arteries and/or veins.
  • the inflammation may be focal, meaning that it affects a single location within a vessel; or it may be widespread, with areas of inflammation scattered throughout a particular organ or tissue, or even affecting more than one organ system in the body.
  • Vasculitis include, without limitation, Buerger's disease (thromboangiitis obliterans), cerebral vasculitis (central nervous system vasculitis), Churg-Strauss arteritis, cryoglobulinemia, essential cryoglobulinemic vasculitis, giant cell (temporal) arteritis, Golfer's vasculitis, Henoch-Schonlein purpura, hypersensitivity vasculitis (allergic vasculitis), Kawasaki disease, microscopic polyarteritis/polyangiitis, polyarteritis nodosa, polymyalgia rheumatica (PMR), rheumatoid vasculitis, Takayasu arteritis, Wegener's granulomatosis, and vasculitis secondary to connective tissue disorders like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, Behpet
  • a chronic inflammation comprises a skin disorder.
  • Skin disorders include, without limitation, an acne, including acne vulgaris, a bullous phemigoid, a dermatitis, including atopic dermatitis and chronic actinic dermatitis, an eczema like atopic eczema, contact eczema, xerotic eczema, seborrhoeic dermatitis, dyshidrosis, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis, and autoeczematization, and statis dermatitis, hidradenitis suppurativa, lichen planus, psoriasis including plaqure psoriasis, nail psoriasis, guttate psoriasis, scalp psoriasis, inverse psoriasis, pustular
  • a chronic inflammation comprises a gastrointestinal disorder.
  • a gastrointestinal disorder includes, without limitation, irritable bowel disease, an inflammatory bowel disease including Crohn's disease and an ulcerative colitis like ulcerative proctitis, left-sided colitis, pancolitis and fulminant colitis.
  • a chronic inflammation comprises a cardiovascular disease.
  • LDL cholesterol becomes embedded in arterial walls, it can invoke an immune response.
  • Chronic inflammation eventually can damage the arteries, which can cause them to burst.
  • Cardiovascular disease is any of a number of specific diseases that affect the heart itself and/or the blood vessel system, especially the veins and arteries leading to and from the heart.
  • cardiovascular disorders including, without limitation, a hypertension, endocarditis, myocarditis, heart valve dysfunction, congestive heart failure, myocardial infarction, a diabetic cardiac conditions, blood vessel inflammation like arteritis, phlebitis, vasculitis; arterial occlusive disease like arteriosclerosis and stenosis, inflammatory cardiomegaly, a peripheral arterial disease; an aneurysm; an embolism; a dissection; a pseudoaneurysm; a vascular malformation; a vascular nevus; a thrombosis; a thrombphlebitis; a varicose veins; a stroke.
  • a hypertension endocarditis, myocarditis, heart valve dysfunction, congestive heart failure, myocardial infarction, a diabetic cardiac conditions, blood vessel inflammation like arteritis, phlebitis, vasculitis; arterial occlusive disease like arteriosclerosis and steno
  • Symptoms of a cardiovascular disorder affecting the heart include, without limitation, chest pain or chest discomfort (angina), pain in one or both arms, the left shoulder, neck, jaw, or back, shortness of breath, dizziness, faster heartbeats, nausea, abnormal heartbeats, feeling fatigued.
  • Symptoms of a cardiovascular disorder affecting the brain include, without limitation, sudden numbness or weakness of the face, arm, or leg, especially on one side of the body, sudden confusion or trouble speaking or understanding speech, sudden trouble seeing in one or both eyes, sudden dizziness, difficulty walking, or loss of balance or coordination, sudden severe headache with no known cause.
  • Symptoms of a cardiovascular disorder affecting the legs, pelvis and/or arm include, without limitation, claudication, which is a pain, ache, or cramp in the muscles, and cold or numb feeling in the feet or toes, especially at night.
  • a chronic inflammation comprises a cancer.
  • Inflammation orchestrates the microenvironment around tumors, contributing to proliferation, survival, and migration.
  • fibrinous inflammation results from a large increase in vascular permeability which allows fibrin to pass through the blood vessels.
  • an appropriate procoagulative stimulus such as cancer cells, a fibrinous exudate is deposited. This is commonly seen in serous cavities, where the conversion of fibrinous exudate into a scar can occur between serous membranes, limiting their function.
  • a cancer is an inflammatory cancer like a NF-KB-driven inflammatory cancer.
  • a chronic inflammation comprises a pharmacologically induced inflammation.
  • Certain drugs or exogenic chemical compounds are known to affect inflammation.
  • Vitamin A deficiency causes an increase in an inflammatory response.
  • Certain illicit drugs such as cocaine and ecstasy may exert some of their detrimental effects by activating transcription factors intimately involved with inflammation (e.g. NF-KB).
  • a chronic inflammation comprises an infection.
  • An infectious organism can escape the confines of the immediate tissue via the circulatory system or lymphatic system, where it may spread to other parts of the body. If an organism is not contained by the actions of acute inflammation, it may gain access to the lymphatic system via nearby lymph vessels.
  • An infection of the lymph vessels is known as lymphangitis, and infection of a lymph node is known as lymphadenitis.
  • lymphadenitis An infection of the lymph vessels is known as lymphangitis, and infection of a lymph node is known as lymphadenitis.
  • a pathogen can gain access to the bloodstream through lymphatic drainage into the circulatory system. Infections include, without limitation, bacterial cystitis, bacterial encephalitis, pandemic influenza, viral encephalitis, and viral hepatitis (A, B and C).
  • a chronic inflammation comprises a tissue or organ injury.
  • Tissue or organ injuries include, without limitation, a burn, a laceration, a wound, a puncture, or a trauma.
  • a chronic inflammation comprises a transplant rejection.
  • Transplant rejection occurs when a transplanted organ or tissue is not accepted by the body of the transplant recipient because the immune system of the recipient attacks the transplanted organ or tissue.
  • An adaptive immune response, transplant rejection is mediated through both T cell mediated and humoral immune (antibodies) mechanisms.
  • a transplant rejection can be classified as a hyperacute rejection, an acute rejection, or a chronic rejection.
  • Chronic rejection of a transplanted organ or tissue is where the rejection is due to a poorly understood chronic inflammatory and immune response against the transplanted tissue.
  • GVHD graft-versus-host disease
  • GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. It can also take place in a blood transfusion under certain circumstances. GVHD is divided into acute and chronic forms. Acute and chronic GVHD appear to involve different immune cell subsets, different cytokine profiles, somewhat different host targets, and respond differently to treatment.
  • a chronic inflammation comprises a Th1-mediated inflammatory disease.
  • an immune response should result in a well-balanced pro- inflammatory Th1 response and anti-inflammatory Th2 response that is suited to address the immune challenge.
  • Th2 type cytokines such as, e.g., IL-4, IL-5, and IL-13 which are associated with the promotion of IgE and eosinophilic responses in atopy, and also IL-10, which has an antiinflammatory response.
  • Th1-mediated inflammatory disease involves an excessive pro-inflammatory response produced by Th1 cells that leads to chronic inflammation.
  • the Th1-mediated disease may be virally, bacterially or chemically (e.g. environmentally) induced.
  • a virus causing the Th1- mediated disease may cause a chronic or acute infection, which may cause a respiratory disorder or influenza.
  • Neuroinflammation is an inflammatory response of the nervous tissue and can be both acute and chronic. Acute neuroinflammatory responses are a well-established defense against harmful conditions, such as infections, toxins, and neuronal cell injury. With respect to the peripheral nervous system (PNS), a neuroinflammatory response is handled in a manner similar to an inflammatory response.
  • the central nervous system (CNS) is considered an immunologically privileged site since the blood-brain barrier (BBB) typically prevents peripheral immune cells from entering the CNS. Instead, in response to an inflammatory trigger, resident glia cells, called microglia, become activated to destroy infectious agents before they damage neural tissue, and as such, are main form of active immune defense in the CNS.
  • microglia become chronically activated, leading to overproduction of proinflammatory factors (i.e., cytokines) and a progression of neurodegenerative changes (e.g., atrophy and loss of function of neurons).
  • proinflammatory factors i.e., cytokines
  • neurodegenerative changes e.g., atrophy and loss of function of neurons.
  • Activation of chronic neuroinflammation further triggers the infiltration of immune cells from the periphery across the BBB, accelerating neuroinflammation and the neurodegenerative process.
  • Much research has focused on the central role of neuroinflammation in the pathogenesis of many conditions relating to the CNS, including e.g., traumatic brain injury, stroke, Alzheimer’s disease, post-operative cognitive decline/perioperative neurocognitive disorder and now even long-term cognitive side effects from SARS-CoV-2.
  • a chronic inflammation comprises a chronic neurogenic inflammation.
  • Chronic neurogenic Inflammation refers to an inflammatory response initiated and/or maintained through the release of inflammatory molecules like SP or CGRP which released from peripheral sensory nerve terminals (/.e., an efferent function, in contrast to the normal afferent signaling to the spinal cord in these nerves).
  • Chronic neurogenic inflammation includes both primary inflammation and secondary neurogenic inflammation.
  • primary neurogenic inflammation refers to tissue inflammation (inflammatory symptoms) that is initiated by, or results from, the release of substances from primary sensory nerve terminals (such as C and A-delta fibers).
  • secondary neurogenic inflammation refers to tissue inflammation initiated by non-neuronal sources (e.g., extravasation from vascular bed or tissue interstitium-derived, such as from mast cells or immune cells) of inflammatory mediators, such as peptides or cytokines, stimulating sensory nerve terminals and causing a release of inflammatory mediators from the nerves.
  • inflammatory mediators such as peptides or cytokines
  • the net effect of both forms (primary and secondary) of chronic neurogenic inflammation is to have an inflammatory state that is maintained by the sensitization of the peripheral sensory nerve fibers.
  • the physiological consequence of the resulting chronic neurogenic inflammation depends on the tissue in question, producing, such as, e.g., cutaneous pain (allodynia, hyperalgesia), joint pain and/or arthritis, visceral pain and dysfunction, pulmonary dysfunction (asthma, COPD), and bladder dysfunction (pain, overactive bladder).
  • Neuroinflammation includes both acute neuroinflammation and chronic neuroinflammation.
  • Acute neuroinflammation usually follows injury to the central nervous system immediately, and is characterized by rapid activation of microglia, release of inflammatory molecules, endothelial cell activation, platelet deposition, and tissue edema.
  • Chronic neuroinflammation is the sustained activation of glial cells and recruitment of other immune cells into the brain.
  • chronic inflammation causes the degradation of tissue and of the BBB and reactive oxygen species generated and inflammatory signals released by microglia recruit peripheral immune cells to assist in mounting a neuroimmune response.
  • a neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death.
  • Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable.
  • the two major contributing factors to neurodegeneration are oxidative stress and neuroinflammation.
  • aspects of the present specification disclose, in part, a disease or disorder that is a renal disease or disorder.
  • a composition or compound is administered to an individual.
  • An individual is typically a human being.
  • any individual who is a candidate for a conventional chronic inflammation and/or a neuroinflammation treatment is a candidate for a disease or disorder treatment disclosed herein.
  • Preoperative evaluation typically includes routine history and physical examination including biomarker evaluation in addition to thorough informed consent disclosing all relevant risks and benefits of the procedure.
  • a pharmaceutical composition disclosed herein may comprise a therapeutic compound in a therapeutically effective amount.
  • the term “effective amount” is synonymous with “therapeutically effective amount”, “effective dose”, or “therapeutically effective dose” and when used in reference to treating a disease or disorder refers to the minimum dose of a therapeutic compound disclosed herein necessary to achieve the desired therapeutic effect and includes a dose sufficient to reduce a symptom associated with a disease or disorder.
  • the effectiveness of a therapeutic compound disclosed herein in treating a disease or disorder can be determined by observing an improvement in an individual based upon one or more clinical symptoms, and/or physiological indicators associated with the condition. An improvement in a disease or disorder also can be indicated by a reduced need for a concurrent therapy.
  • the appropriate effective amount of a therapeutic compound disclosed herein to be administered to an individual for a particular chronic inflammation and/or a neuroinflammation can be determined by a person of ordinary skill in the art by taking into account factors, including, without limitation, the type of chronic inflammation and/or a neuroinflammation, the location of the chronic inflammation and/or a neuroinflammation, the cause of the chronic inflammation and/or a neuroinflammation, the severity of the chronic inflammation and/or a neuroinflammation, the degree of relief desired, the duration of relief desired, the particular therapeutic compound used, the pharmacokinetic properties of the particular therapeutic compound used including liberation, absorption, distribution, metabolism, and excretion, the pharmacodynamic properties of the particular therapeutic compound used including mechanism of action, dose-response relationship, desired activity, undesirable side effects, therapeutic window and duration of action, the nature of the other compounds to be included in the composition, the particular formulation, the particular route of administration, the particular characteristics, history and risk factors of the patient, such as, e.g., age
  • an effective amount of a therapeutic compound disclosed herein can be extrapolated from in-vitro assays and in-vivo administration studies using animal models prior to administration to humans.
  • variations in the necessary effective amount are to be expected in view of the differing efficiencies of the various routes of administration.
  • oral administration of a therapeutic compound disclosed herein generally would be expected to require higher dosage levels than intravenous administration.
  • systemic administration of a therapeutic compound disclosed herein would be expected to require higher dosage levels than a local administration. Variations in these dosage levels can be adjusted using standard empirical routines of optimization, which are well-known to a person of ordinary skill in the art.
  • the condition of the individual can be monitored throughout the course of a method or use disclosed herein and that the effective amount of a therapeutic compound disclosed herein that is administered can be adjusted accordingly.
  • the precise therapeutically effective dosage levels and patterns are preferably determined by the attending healthcare professional in consideration of the above-identified factors.
  • a therapeutically effective amount of a therapeutic compound disclosed herein reduces a symptom associated with a disease or disorder by, e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 100%.
  • a therapeutically effective amount of a therapeutic compound disclosed herein reduces a symptom associated with a disease or disorder by, e.g., at most 10%, at most 15%, at most 20%, at most 25%, at most 30%, at most 35%, at most 40%, at most 45%, at most 50%, at most 55%, at most 60%, at most 65%, at most 70%, at most 75%, at most 80%, at most 85%, at most 90%, at most 95% or at most 100%.
  • a therapeutically effective amount of a therapeutic compound disclosed herein reduces a symptom associated with a disease or disorder by, e.g., about 10% to about 100%, about 10% to about 90%, about
  • a therapeutically effective amount of a therapeutic compound disclosed herein generally is in the range of about 0. 01 mg/kg to about 10 mg/kg.
  • an effective amount of a therapeutic compound disclosed herein may be, e.g., at least 0.01 mg/kg, at least 0.05 mg/kg, at least 0.1 mg/kg, at least 0.5 mg/kg, at least 1.0 mg/kg, at least 2.0 mg/kg, at least 3.0 mg/kg, at least 4.0 mg/kg, at least 5.0 mg/kg, at least 6.0 mg/kg, at least 7.0 mg/kg, at least 8.0 mg/kg, at least 9.0 mg/kg, or at least 10 mg/kg.
  • an effective amount of a therapeutic compound disclosed herein may be, e.g., at most 0.01 mg/kg, at most 0.05 mg/kg, at most 0.1 mg/kg, at most 0.5 mg/kg, at most 1.0 mg/kg, at most 2.0 mg/kg, at most 3.0 mg/kg, at most 4.0 mg/kg, at most 5.0 mg/kg, at most 6.0 mg/kg, at most 7.0 mg/kg, at most 8.0 mg/kg, at most 9.0 mg/kg, or at most 10 mg/kg.
  • an effective amount of a therapeutic compound disclosed herein may be in the range of, e.g., about 0.01 mg/kg to about 0.05 mg/kg, about 0.01 mg/kg to about 0.1 mg/kg, about 0.01 mg/kg to about 0.5 mg/kg, about 0.01 mg/kg to about 1.0 mg/kg, about 0.01 mg/kg to about 2.0 mg/kg, about 0.01 mg/kg to about 3.0 mg/kg, about 0.01 mg/kg to about 4.0 mg/kg, about 0.01 mg/kg to about 5.0 mg/kg, about 0.01 mg/kg to about 6.0 mg/kg, about 0.01 mg/kg to about 7.0 mg/kg, about 0.01 mg/kg to about 8.0 mg/kg, about 0.01 mg/kg to about 9.0 mg/kg, about 0.01 mg/kg to about 10 mg/kg, about 0.1 mg/kg to about 0.5 mg/kg, about 0.1 mg/kg to about 1.0 mg/kg, about 0.1 mg/kg to about 2.0 mg/kg, about
  • a therapeutically effective amount of a therapeutic compound disclosed herein generally is in the range of about 0. 01 mg/kg/day to about 10 mg/kg/day.
  • an effective amount of a therapeutic compound disclosed herein may be, e.g., at least 0.01 mg/kg/day, at least 0.05 mg/kg/day, at least 0.1 mg/kg/day, at least 0.5 mg/kg/day, at least 1.0 mg/kg/day, at least 2.0 mg/kg/day, at least 3.0 mg/kg/day, at least 4.0 mg/kg/day, at least 5.0 mg/kg/day, at least 6.0 mg/kg/day, at least 7.0 mg/kg/day, at least 8.0 mg/kg/day, at least 9.0 mg/kg/day, or at least 10 mg/kg/day.
  • an effective amount of a therapeutic compound disclosed herein may be, e.g., at most 0.01 mg/kg/day, at most 0.05 mg/kg/day, at most 0.1 mg/kg/day, at most 0.5 mg/kg/day, at most 1.0 mg/kg/day, at most 2.0 mg/kg/day, at most 3.0 mg/kg/day, at most 4.0 mg/kg/day, at most 5.0 mg/kg/day, at most 6.0 mg/kg/day, at most 7.0 mg/kg/day, at most 8.0 mg/kg/day, at most 9.0 mg/kg/day, or at most 10 mg/kg/day.
  • an effective amount of a therapeutic compound disclosed herein may be in the range of, e.g., about 0.01 mg/kg/day to about 0.05 mg/kg/day, about 0.01 mg/kg/day to about 0.1 mg/kg/day, about 0.01 mg/kg/day to about 0.5 mg/kg/day, about 0.01 mg/kg/day to about 1.0 mg/kg/day, about 0.01 mg/kg/day to about 2.0 mg/kg/day, about 0.01 mg/kg/day to about 3.0 mg/kg/day, about 0.01 mg/kg/day to about 4.0 mg/kg/day, about 0.01 mg/kg/day to about 5.0 mg/kg/day, about 0.01 mg/kg/day to about 6.0 mg/kg/day, about 0.01 mg/kg/day to about 7.0 mg/kg/day, about 0.01 mg/kg/day to about 8.0 mg/kg/day, about 0.01 mg/kg/day to about 9.0 mg/kg/day, about 0.01 mg/kg/kg/
  • Dosing can be single dosage or cumulative (serial dosing), and can be readily determined by one skilled in the art.
  • treatment of a disease or disorder may comprise a one-time administration of an effective dose of a pharmaceutical composition disclosed herein.
  • treatment of a disease or disorder may comprise multiple administrations of an effective dose of a pharmaceutical composition carried out over a range of time periods, such as, e.g., once daily, twice daily, trice daily, once every few days, or once weekly.
  • the timing of administration can vary from individual to individual, depending upon such factors as the severity of an individual's symptoms.
  • an effective dose of a pharmaceutical composition disclosed herein can be administered to an individual once daily for an indefinite period of time, or until the individual no longer requires therapy.
  • a person of ordinary skill in the art will recognize that the condition of the individual can be monitored throughout the course of treatment and that the effective amount of a pharmaceutical composition disclosed herein that is administered can be adjusted accordingly.
  • a pharmaceutical composition comprising a therapeutic compound disclosed herein results in a bio-distribution of the therapeutic compound different than a bio-distribution of the therapeutic compound included in the same pharmaceutical composition, except without the one or more digestion enhancers disclosed herein.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, and about 15% to about 35% by weight of one or more free C 14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 15% to about 35% by weight of one or more free Ci 4-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, Cio-C24 di- and C10-C24 triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising C10- C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cis di- and CIB-CIS triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB-CIS triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and Cie-Cis triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14- 24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14-24 fatty acids. In some embodiments, a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 faty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14- 24 faty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising C10- C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, CIB-CIS di- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and CIB-CIS triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB- CIS mono-, Cie-Cisdi- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of one or more protein kinase inhibitors, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 1 % to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14- 24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, about 1 % to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising C10- C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, CIB-CIS di- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and CIB-CIS triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB- CIS mono-, Cie-Cisdi- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 1 % to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C-14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C-14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10- C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C 14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, CIB-CIB di- and CIB-CIB triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cisdi- and CIB-CIB triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie-C-is mono-, Cie-Cisdi- and CIB-CIB triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB- CIS mono-, Cie-Cisdi- and CIB-CIB triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cis di- and CIB-CIB triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie-C-is mono-, Cie-Cisdi- and CIB-CIB triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10- C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, CIB-CIS di- and CIB-CIS triglycerides, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, CIB-CIB di- and CIB-CIB triglycerides, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie-C-is mono-, Cie-Cisdi- and CIB-CIB triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB- CIS mono-, Cie-Cisdi- and CIB-CIB triglycerides, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cis di- and CIB-CIB triglycerides, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of one or more protein kinase inhibitors, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie-C-is mono-, Cie-Cisdi- and CIB-CIB triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the protein kinase inhibitor in the above embodiments comprises a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, or both.
  • the serine/threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, ROCK 2 kinase inhibitor, or both.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, one or more hard fats, one or more liquid fats, and one or more free C14-24 fatty acids. In some embodiments, a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, one or more hard fats, one or more liquid fats, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1H-Pyrazol-4- yl)phenyl]amino]py rimidin-2-y l]-1 -methyl-1 H-indol-2-y I] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, one or more hard fats, one or more liquid fats, one or more bile acids, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1H-Pyrazol-4-yl)phenyl]amino]pyrimidin- 2-yl]-1 -methyl-1 H-indol-2-y I] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1 H- Pyrazol-4-yl)phenyl]amino]pyrimidin-2-yl]-1-methyl-1 H-indol-2-yl] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, one or more hard fats, one or more liquid fats, one or more bile acids, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1H-Pyrazol-4-yl)phenyl]amino]pyrimidin- 2-yl]-1 -methyl-1 H-indol-2-y I] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1H-Pyrazol-4-yl)phenyl]amino]pyrimidin- 2-y l]-1 -methyl-1 H-indol-2-y I] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1 H- Pyrazol-4-yl)phenyl]amino]pyrimidin-2-yl]-1-methyl-1 H-indol-2-yl] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a ROCK 2 kinase inhibitor about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1 H-Pyrazol-4- yl)phenyl]amino]pyrimidin-2-yl]-1-methyl-1 H-indol-2-yl] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C16-C18 mono-, Cie-Cis di- and Cie-Cis triglycerides, and about 15% to about 35% by weight of one or more free Ci 4-24 fatty acids.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie-Cis mono-, Cie-Cisdi- and Cie-Cis triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie-Cis mono-, Cie-Cis di- and Cie-Cis triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a ROCK 2 kinase inhibitor about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30%
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1H-Pyrazol-4-yl)phenyl]amino]pyrimidin- 2-y l]-1 -methyl-1 H-indol-2-y I] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats, about 30% to about 55% by weight of one or more liquid fats, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1 H-Pyrazol-4-yl)phenyl]amino]pyrimidin-2-yl]-1-methyl-1 H-i ndol-2-y I] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising glycerolipids, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1 H- Pyrazol-4-yl)phenyl]amino]pyrimidin-2-yl]-1-methyl-1 H-indol-2-yl] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 15% to about 35% by weight of one or more free Ci 4-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising C10-C24 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1 H-Pyrazol-4- yl)phenyl]amino]pyrimidin-2-yl]-1-methyl-1 H-indol-2-yl] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie- Cis mono-, Cie-Cisdi- and Cie-Cis triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie-Cis mono-, Cie-Cis di- and Cie-Cis triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie- Cis mono-, Cie-Cis di- and Cie-Cis triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cisdi- and CIB-CIS triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB- CIS triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB- CIS triglycerides, and about 15% to about 35% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and CIB-CIS triglycerides, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a ROCK 2 kinase inhibitor, about 25% to about 35% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 30% to about 55% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and CIB-CIS triglycerides, about 2% to about 6% by weight of one or more bile acids, about 15% to about 35% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the ROCK 2 kinase inhibitor in the above embodiments comprises [6-[4-[[4-(1 H-Pyrazol-4-yl)phenyl]amino]pyrimidin-2-yl]-1-methyl-1 H-i ndol-2-y I] (3,3-difluoroazetidin-1-yl)methanone, monohydrochloride, monohydrate.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a mebendazole, one or more hard fats, one or more liquid fats, and one or more free C14-24 fatty acids. In some embodiments, a pharmaceutical composition comprises a mebendazole, one or more hard fats, one or more liquid fats, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants. In some embodiments, a pharmaceutical composition comprises a mebendazole, one or more hard fats, one or more liquid fats, one or more bile acids, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about a mebendazole, about 40% to about 55% by weight of one or more hard fats, about 20% to about 30% by weight of one or more liquid fats, and about 20% to about 30% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats, about 20% to about 30% by weight of one or more liquid fats, about 20% to about 30% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats, about 20% to about 30% by weight of one or more liquid fats, about 2% to about 6% by weight of one or more bile acids, about 20% to about 30% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 30% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 30% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 2% to about 6% by weight of one or more bile acids, about 20% to about 30% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 20% to about 30% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 30% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 2% to about 6% by weight of one or more bile acids, about 20% to about 30% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cisdi- and CIB-CIB triglycerides, and about 20% to about 30% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cis di- and CIB-CIB triglycerides, about 20% to about 30% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises a mebendazole, about 40% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 30% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cisdi- and CIB- CIS triglycerides, about 2% to about 6% by weight of one or more bile acids, about 20% to about 30% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14- 24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14- 24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mLto about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats, about 20% to about 40% by weight of one or more liquid fats, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 1 % to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14- 24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono- , Cie-Cis di- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono- , Cie-Cis di- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and CIB-CIS triglycerides, about 1 % to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, CIB-CIS di- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 10 mg/mL to about 150 mg/mL of a mebendazole, about 35% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 40% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono- , Cie-Cis di- and CIB-CIS triglycerides, about 1% to about 6% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 2% to about 7% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises an olaparib, one or more hard fats, one or more liquid fats, and one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises an olaparib, one or more hard fats, one or more liquid fats, ne or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises an olaparib, one or more hard fats, one or more liquid fats, one or more bile acids, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about an olaparib, about 28% to about 38% by weight of one or more hard fats, about 28% to about 38% by weight of one or more liquid fats, and about 28% to about 38% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats, about 28% to about 38% by weight of one or more liquid fats, about 28% to about 38% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats, about 28% to about 38% by weight of one or more liquid fats, about 2% to about 6% by weight of one or more bile acids, about 28% to about 38% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising glycerolipids, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 28% to about 38% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising glycerolipids, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 28% to about 38% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising glycerolipids, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 2% to about 6% by weight of one or more bile acids, about 28% to about 38% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14- 24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising C10-C24 triglycerides, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono- , C10-C24 di- and C10-C24 triglycerides, and about 28% to about 38% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising C10-C24 triglycerides, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 28% to about 38% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising C10-C24 triglycerides, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10- C24 di- and C10-C24 triglycerides, about 2% to about 6% by weight of one or more bile acids, about 28% to about 38% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, CIB-CIS di- and CIB-CIS triglycerides, and about 28% to about 38% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 28% to about 38% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises an olaparib, about 28% to about 38% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 28% to about 38% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB-CIS triglycerides, about 2% to about 6% by weight of one or more bile acids, about 28% to about 38% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14- 24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10- C24 di- and C10-C24 triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10- C24 triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cis di- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB-CIS triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono- , Cie-Cis di- and CIB-CIS triglycerides, and about 20% to about 55% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cis di- and CIB-CIS triglycerides, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of an olaparib, about 25% to about 55% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C16-C18 mono-, C16-C18 di- and C16-C18 triglycerides, about 1% to about 7% by weight of one or more bile acids, about 20% to about 55% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a nintedanib free base, one or more hard fats, one or more liquid fats, and one or more free C14-24 fatty acids
  • a pharmaceutical composition comprises a nintedanib free base, one or more hard fats, one or more liquid fats, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a nintedanib free base, one or more hard fats, one or more liquid fats, one or more bile acids, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono- , di- and triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10- C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14- 24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cis di- and CIB-CIB triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, Cie-Cis di- and CIB-CIB triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB- CIS mono-, CIB-CIS di- and CIB-CIB triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14- 24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising glycerolipids, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed glycerolipids including a mixture of mono-, di- and triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono- , C10-C24 di- and C10-C24 triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising C10-C24 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of C10-C24 mono-, C10-C24 di- and C10-C24 triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of Cie- Cis mono-, Cie-Cisdi- and Cie-Cis triglycerides, and about 30% to about 40% by weight of one or more free C-14-24 fatty acids.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIB mono-, CIB-CIS di- and CIB-CIS triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 0.5% to about 20% by weight of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB- CIS mono-, CIB-CIS di- and CIB-CIS triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB-CIS triglycerides, and about 30% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB- CIS triglycerides, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises about 30 mg/mL to about 300 mg/mL of a nintedanib free base, about 30% to about 40% by weight of one or more hard fats comprising a mixture of saturated C10-C18 triglycerides and/or saturated C12-C18 triglycerides, about 20% to about 35% by weight of one or more liquid fats comprising partially hydrolyzed triglycerides including a mixture of CIB-CIS mono-, Cie-Cisdi- and CIB- CIS triglycerides, about 0.5% to about 6% by weight of one or more bile acids, about 30% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a nintedanib salt, one or more hard fats, one or more liquid fats, and one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a nintedanib salt, one or more hard fats, one or more liquid fats, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • a pharmaceutical composition comprises a nintedanib salt, one or more hard fats, one or more liquid fats, one or more bile acids, one or more free C14-24 fatty acids, and one or more free C14-24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid and the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the one or more bile acids in the above embodiments comprises cholic acid
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.
  • the oleate alkali metal or alkali earth metal salt in the above embodiments is a sodium oleate
  • the stearate alkali metal or alkali earth metal salt in the above embodiments is a sodium stearate
  • the linoleate alkali metal or alkali earth metal salt in the above embodiments is a sodium linoleate.
  • a pharmaceutical composition comprises a nintedanib salt, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, and about 20% to about 40% by weight of one or more free C14-24 fatty acids.
  • a pharmaceutical composition comprises a nintedanib salt, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • a pharmaceutical composition comprises a nintedanib salt, about 30% to about 40% by weight of one or more hard fats, about 20% to about 35% by weight of one or more liquid fats, about 0.5% to about 6% by weight of one or more bile acids, about 20% to about 40% by weight of one or more free C14-24 fatty acids, and about 0.5% to about 5% by weight of one or more free C14- 24 fatty acid surfactants.
  • the one or more bile acids in the above embodiments comprises cholic acid.
  • the one or more free C14-24 fatty acids in the above embodiments comprises one or more free C14-18 fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof.
  • the one or more free C14-24 fatty acid surfactants in the above embodiments comprises one or more free C14-18 fatty acid surfactants, preferably an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Botany (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Nanotechnology (AREA)
  • Optics & Photonics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention divulgue une composition pharmaceutique comprenant un ou plusieurs fibrates, un ou plusieurs glycérolipides et un ou plusieurs activateurs de digestion. Les glycérolipides divulgués comprennent une ou plusieurs graisses solides et une ou plusieurs graisses liquides. Les amplificateurs de digestion divulgués comprennent un ou plusieurs acides biliaires, un ou plusieurs phospholipides, un ou plusieurs acides gras libres en C14-24, un ou plusieurs tensioactifs d'acides gras libres en C14-24 ou une combinaison quelconque associée. La présente invention divulgue également des méthodes et des procédures destinées à formuler lesdits un ou plusieurs fibrates divulgués dans les compositions pharmaceutiques divulguées. La présente invention divulgue en outre des méthodes et des utilisations des compositions pharmaceutiques divulguées dans le traitement d'une inflammation et/ou d'une neuro-inflammation.
EP23710760.2A 2022-03-14 2023-03-14 Compositions possédant une biodisponibilité améliorée d'agents thérapeutiques et leurs utilisations Pending EP4493151A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202263269330P 2022-03-14 2022-03-14
PCT/EP2022/058180 WO2022207580A2 (fr) 2021-03-27 2022-03-28 Compositions ayant une biodisponibilité d'agents thérapeutiques améliorée
PCT/EP2023/056506 WO2023174948A2 (fr) 2022-03-14 2023-03-14 Compositions possédant une biodisponibilité améliorée d'agents thérapeutiques et leurs utilisations

Publications (1)

Publication Number Publication Date
EP4493151A2 true EP4493151A2 (fr) 2025-01-22

Family

ID=85571360

Family Applications (1)

Application Number Title Priority Date Filing Date
EP23710760.2A Pending EP4493151A2 (fr) 2022-03-14 2023-03-14 Compositions possédant une biodisponibilité améliorée d'agents thérapeutiques et leurs utilisations

Country Status (7)

Country Link
EP (1) EP4493151A2 (fr)
JP (1) JP2025509680A (fr)
AU (1) AU2023233811A1 (fr)
CA (1) CA3245873A1 (fr)
IL (1) IL315617A (fr)
WO (1) WO2023174948A2 (fr)
ZA (1) ZA202407659B (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025072929A1 (fr) * 2023-09-28 2025-04-03 The Regents Of The University Of California Méthodes et compositions de traitement d'états liés à l'âge
WO2025093572A1 (fr) * 2023-10-29 2025-05-08 TRx Biosciences Limited Compositions de dispersion solide et leurs utilisations
WO2026053168A1 (fr) * 2024-09-06 2026-03-12 Graviton Bioscience Bv Formes amorphes d'un inhibiteur de rock2 et formulations associées

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5082667A (en) * 1988-06-07 1992-01-21 Abbott Laboratories Solid pharmaceutical dosage in tablet triturate form and method of producing same
US5885486A (en) * 1993-03-05 1999-03-23 Pharmaciaand Upjohn Ab Solid lipid particles, particles of bioactive agents and methods for the manufacture and use thereof
US20020028813A1 (en) * 1997-09-03 2002-03-07 Paul F. Jackson Thioalkyl compounds, methods, and compositions for inhibiting parp activity
US6063768A (en) 1997-09-04 2000-05-16 First; Eric R. Application of botulinum toxin to the management of neurogenic inflammatory disorders
US20060138059A1 (en) 2004-12-28 2006-06-29 Vair Larry L Jr Corona-treated polypropylene liquid filtration media
EP2220073B1 (fr) * 2007-11-15 2014-09-03 MSD Italia S.r.l. Derivés de pyridazinone inhibiteurs de la parp
ME02640B (fr) * 2008-10-07 2017-06-20 Kudos Pharm Ltd Formulation pharmaceutique 514
CN102307576A (zh) * 2008-12-15 2012-01-04 班纳制药公司 用于增强水不溶性活性剂的释放和吸收的方法
CN101507707B (zh) * 2009-04-08 2011-01-19 邓菊娟 一种盐酸法舒地尔脂微球制剂及其制备方法
CN101926757B (zh) * 2010-09-01 2013-01-02 北京大学 一种难溶性药物的液体组合物及其制备方法
CN102813639B (zh) * 2011-06-08 2014-04-30 中国疾病预防控制中心寄生虫病预防控制所 甲苯达唑软胶囊剂
CA2865040C (fr) * 2012-02-21 2020-07-14 Merck Patent Gmbh Derives cycliques de diaminopyrimidine
EA201690608A1 (ru) * 2013-12-04 2016-12-30 Джилид Сайэнс, Инк. Способы лечения раковых заболеваний
US11629118B2 (en) * 2017-03-03 2023-04-18 Inspirna, Inc. Formulations with improved stability
AU2019363244B2 (en) * 2018-10-15 2024-10-03 Cipla Limited Pharmaceutical formulation
WO2020217235A1 (fr) * 2019-04-24 2020-10-29 Aizant Drug Research Solutions Private Limited Forme posologique solide de dasatinib
CN113546045B (zh) * 2021-08-18 2022-11-11 浙江大学 恢复肿瘤微环境失活树突状细胞功能的纳米制剂及应用

Also Published As

Publication number Publication date
WO2023174948A3 (fr) 2023-10-26
IL315617A (en) 2024-11-01
CA3245873A1 (fr) 2023-09-21
AU2023233811A1 (en) 2024-09-19
JP2025509680A (ja) 2025-04-11
ZA202407659B (en) 2026-01-28
WO2023174948A2 (fr) 2023-09-21

Similar Documents

Publication Publication Date Title
EP4493151A2 (fr) Compositions possédant une biodisponibilité améliorée d'agents thérapeutiques et leurs utilisations
Rizvi et al. Simvastatin-loaded solid lipid nanoparticles for enhanced anti-hyperlipidemic activity in hyperlipidemia animal model
US6720001B2 (en) Emulsion compositions for polyfunctional active ingredients
AU2016245984B2 (en) Self-emulsifying formulations of DIM-related indoles
Jiang et al. Ionic Liquids: Promising Approach for Oral Drug Delivery: Jiang et al.
CN103002877A (zh) 作为缓解疾病的抗风湿性药（dmard）和抗癌药剂的甲氨蝶呤的持续释放制剂
AU2022248850A1 (en) Compositions having improved bioavailability of therapeutics
TW202139984A (zh) 治療性化合物及其調配物與用途
Pangeni et al. Improvements in the oral absorption and anticancer efficacy of an oxaliplatin-loaded solid formulation: pharmacokinetic properties in rats and nonhuman primates and the effects of oral metronomic dosing on colorectal cancer
CN101780037B (zh) 双嘧达莫自乳化给药系统及其制备方法
Caliph et al. The impact of lymphatic transport on the systemic disposition of lipophilic drugs
Shailendrakumar et al. Improved oral pharmacokinetics of pentoxifylline with palm oil and capmul® MCM containing self-nano-emulsifying drug delivery system
JP2023520273A (ja) 治療化合物、製剤、およびその使用
AU2026201779A1 (en) Formulated and/or co-formulated liposome compositions containing IDO antagonist prodrugs useful in the treatment of cancer and methods thereof
JP2009518443A (ja) 脂質を主材料とする担体に内封された、不溶性小分子治療剤の製剤
CN104224750A (zh) 一种注射用卡巴他赛白蛋白纳米粒制剂及其制备方法
US20250195433A1 (en) Compositions Having Improved Bioavailability of Therapeutics and Uses Thereof
KR20210099038A (ko) 시클로스포린 유사체의 제약 제형
Gulyakin et al. Solubilization of hydrophobic antitumor drugs
CN104546722B (zh) 米铂脂质体和制法
KR101859200B1 (ko) 모노아세틸디아실글리세롤 화합물의 경구 투여용 조성물 및 고형 제제
JP2026505949A (ja) 自己乳化医薬組成物、その製造方法及び使用
CN111065397A (zh) MEK/PI3K、JAK/MEK、JAK/PI3K/mTOR和MEK/PI3K/mTOR生物学途径的抑制剂和用于改善治疗化合物的淋巴摄取、生物利用度和溶解度的方法
CN104703626B (zh) 用于治疗癌症的基于碘油的抗肿瘤乳剂
US20250195461A1 (en) Fibrate Compositions for Treating Inflammation and Neuroinflammation

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20241011

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC ME MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)