EP3328364A1 - Nouvelle composition orale à double libération retardée de dexlansoprazole - Google Patents

Nouvelle composition orale à double libération retardée de dexlansoprazole

Info

Publication number
EP3328364A1
EP3328364A1 EP16829940.2A EP16829940A EP3328364A1 EP 3328364 A1 EP3328364 A1 EP 3328364A1 EP 16829940 A EP16829940 A EP 16829940A EP 3328364 A1 EP3328364 A1 EP 3328364A1
Authority
EP
European Patent Office
Prior art keywords
release
dexlansoprazole
phthalate
pharmaceutical composition
cellulose
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.)
Withdrawn
Application number
EP16829940.2A
Other languages
German (de)
English (en)
Other versions
EP3328364A4 (fr
Inventor
Anwar Siraj DAUD
Shamsuddin JAMALUDDIN
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.)
ZIM Laboratories Ltd
Original Assignee
ZIM Laboratories 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
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Application filed by ZIM Laboratories Ltd filed Critical ZIM Laboratories Ltd
Publication of EP3328364A1 publication Critical patent/EP3328364A1/fr
Publication of EP3328364A4 publication Critical patent/EP3328364A4/fr
Withdrawn legal-status Critical Current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
    • A61K9/48—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
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • 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
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/5073—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 having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—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 having two or more different coatings optionally including drug-containing subcoatings with drug-free core

Definitions

  • the present disclosure pertains to technical field of pharmaceutical formulation.
  • the present disclosure pertains to novel dual delayed release oral composition of dexlansoprazole or pharmaceutically acceptable salts or hydrated forms thereof, and method of preparation of the same.
  • Dexlansoprazole is a proton pump inhibitor (PPI) that inhibits gastric acid secretion.
  • Chemically Dexlansoprazole is (+)-2-[(R)- ⁇ [3-methyl-4-(2,2,2-trifluoroethoxy) pyridin-2-yl] methyl ⁇ sulfinyl]-lH-benzimidazole.
  • the molecular weight of Dexlansoprazole is about 369.36 and its molecular formula is C16H14F3N302S.
  • Dexlansoprazole is the R-enantiomer of lansoprazole and is represented by compound of structural formu
  • Lansoprazole is described in U. S. Patent No. 4,628,098.
  • the proprietary name of Dexlansoprazole delayed release oral capsule is "DEXILANT" which is marketed by Takeda Pharms in USA.
  • Dexlansoprazole is available as delayed release oral capsule form in 30 mg and 60 mg strengths which was approved on January 30, 2009 to Takeda Pharms, USA. Dexlansoprazole is indicated for healing of all grades of erosive esophagitis (EE), maintaining healing of EE and relief of heartburn and to treating heartburn associated with symptomatic non-erosive gastro esophageal reflux disease (GERD).
  • EE erosive esophagitis
  • GERD gastro esophageal reflux disease
  • Indian Patent Application No. 820/CHE/2009 discloses pharmaceutical compositions comprising a core containing at least one PPI and a coating of modified semi-permeable membrane, which loses its semi-permeable characteristics on exposure to aqueous environment irrespective to the change in pH and allows the drug passage across the coating by diffusion, though maintaining the physical integrity of coating.
  • U.S. Patent No. 8,753,682 discloses the dual release oral tablet of Dexlansoprazole or pharmaceutically acceptable salts or hydrated forms thereof comprising 1) 20% by weight of the Dexlansoprazole in powder form; 2) 80% by weight of the Dexlansoprazole in granule form, wherein the granule form is of different particle size than the powder form; and 3) a single enteric coating that dissolves at between pH 5.5 and 6.4, wherein, upon oral administration, the tablet achieves dual release of the Dexlansoprazole in the small intestine at pH 5.5 and then at pH 6.5, with prevention of dose dumping of the Dexlansoprazole.
  • U.S. Patent No. 8,758,818 discloses dual release oral tablet of Dexlansoprazole comprises Dexlansoprazole in two forms a) powder form and b) granule form and a single enteric coating that dissolves at between pH 5.5 and 6.4, wherein upon oral administration, the tablet achieves dual release of the Dexlansoprazole in that the Dexlansoprazole is released in the small intestine at pH 5.5, and then at pH 6.0 to 6.5, with prevention of dose dumping of the Dexlansoprazole.
  • a first layer comprising: (I) granules, wherein individual granules comprise a core comprising Dexlansoprazole or pharmaceutically acceptable salts or hydrated forms thereof and one or more pharmaceutically acceptable excipients wherein the core is coated with a film, and wherein the film-coated core is coated with an enteric coating that dissolves at pH 5.5 or higher, wherein the enteric coating in the first layer comprises at least one substance selected from cellulose acetate phthalate, cellulose acetate succinate, hydroxpropyl cellulose phthalate, hydroxpropyl ethylcellulose phthalate, hydroxyl propyl methyl cellulose phthalate, hydroxyl propyl methyl cellulose acetate succinate, hydroxyethyl cellulose phthalate, methylcellulose phthalate, polyvinyl acetate phthalate, polyvinylacetate hydrogen phthalate, amylase acetate phthalate, cellulose ester phthalates, cellulose ether phthalates
  • a second layer comprising film-coated granules comprising Dexlansoprazole or pharmaceutically acceptable salts or hydrated forms thereof and one or more pharmaceutically acceptable excipients; wherein the rate controlling agent is in only the first layer and not in the second layer or an optional enteric coating of the entire tablet.
  • U.S. Patent No. 7,790,755 discloses controlled release preparation, in particular a capsule comprising composition (i) comprising a tablet, granule or fine granule wherein the release of active ingredient is controlled; said tablet, granule or fine granule comprising a core particle containing active ingredient and a pH- dependently soluble release-controlled coating-layer which comprises one kind of polymeric substance or a mixture of two or more kinds of polymeric substances having different release properties selected from the group consisting of hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, carboxymethylethyl cellulose, methyl methacrylate-methacrylic acid copolymer(s), methacrylic acid-ethyl acrylate copolymer(s), methacrylic acid-methyl acrylate -methyl methacrylate copolymer(s), hydroxypropyl cellulose acetate succinate, polyvinyl acetate phthalate
  • US'755 further teaches that the active ingredient present in the controlled release preparation is selected from Lansoprazole, an optically active R-isomer of Lansoprazole (Dexlansoprazole) or an optically active S- isomer of Lansoprazole.
  • US'755 claimed dual pulse composition which is based upon the pH-dependently soluble release-controlled coating -layer that releases the active ingredient in dual pulse i.e. (i) first pulse releases the active ingredient at pH range of no less than 5.0, nor more than 6.0 and (ii) second pulse releases the active ingredient at pH range of 6.0 to 7.5.
  • US'755 teaches that a further extension of sustainability becomes possible by combining coating based pH-dependently soluble release-controlled system with a control of migration speed in the gastrointestinal tract.
  • the pH dependent polymer(s) may vary its solubilisation in inter-patient variability or in intra-patient at different physiological conditions in different stages of disease which leads to poor site-specificity of the formulations.
  • the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term "about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
  • aspects of the present disclosure relates to modified release oral pharmaceutical composition of dexlansoprazole or pharmaceutically acceptable salts or hydrated forms thereof having a desired drug release profile.
  • the present disclosure provides a dual delayed release oral pharmaceutical composition of dexlansoprazole or pharmaceutically acceptable salts or hydrated forms thereof that can incorporate two pulsatile release formulations (a) and (b).
  • formulation (a) can include: (i) a core particle comprising dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof, and (ii) a pH-dependent release-controlled layer; and formulation (b) can include: (i) a core particle comprising dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof, (ii) a pH-independent release-controlled layer, and (iii) a pH-dependent release-controlled layer.
  • the modified release oral pharmaceutical composition can release the active ingredient in two pulses i.e. a first pulse of the active ingredient upon administration of the composition to an individual and a second pulse following entry of the composition into the higher pH environment of the intestines.
  • the two pulsatile release formulations of dexlansoprazole may be in the form of pellets, tablets, granules or fine granules.
  • the core particle can be in the form of an active core particle made of dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof.
  • the core particle may be an inert core particle coated with a layer of dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof.
  • the core particles can further incorporate a basic inorganic salt stabilizer, one or more gel-forming polymers and one or more pharmaceutically acceptable excipients.
  • the pH-independent release-controlled layer can be formed of a hydrophilic polymer that can be selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), carboxyvinyl polymer, polyethylene glycol 6000, lactose, mannitol, pullulan, agar, gellan gum, guar gum, carageenan, acacia gum, gum arabic, dextran, pectin and mixtures thereof.
  • HPMC hydroxypropyl methylcellulose
  • HPC hydroxypropylcellulose
  • PVP polyvinylpyrrolidone
  • carboxyvinyl polymer polyethylene glycol 6000
  • lactose lactose
  • mannitol pullulan
  • pullulan agar
  • gellan gum gellan gum
  • guar gum carageenan
  • acacia gum gum arabic
  • dextran dextran
  • the pH-independent release-controlled layer can be formed of a hydrophobic polymer that can be selected from the group consisting of ethyl cellulose, Eudragit® RL, Eudragit® RS, hydrogenated vegetable oils, glyceryl behenate, wax, fatty acid, fatty alcohol, shellac and mixtures thereof.
  • the pH-dependent release-controlled layer can be formed of an enteric coating polymer that can be selected from the group consisting of cellulose acetate trimellitate, methacrylic acid, methyl methacrylate copolymer, cellulose acetate phthalate, cellulose acetate succinate, hydroxypropyl cellulose phthalate, hydroxypropyl ethyl cellulose phthalate, hydroxyl propyl methyl cellulose phthalate, hydroxyl propyl methyl cellulose acetate succinate, hydroxyethyl cellulose phthalate, methylcellulose phthalate, polyvinyl acetate phthalate, polyvinyl acetate hydrogen phthalate, amylase acetate phthalate, cellulose ester phthalates, cellulose ether phthalates, sodium cellulose acetate phthalate, starch acid phthalate, cellulose acetate butyrate, cellulose acetate maleate, cellulose acetate propionate, styrene maleic
  • the pH-dependent release-controlled layer of formulation (a) can dissolve at a pH ranging from 4.5 to 6 to release a first pulse of the active ingredient.
  • the pH-independent soluble release-controlled layer of formulation (b) can dissolve at higher pH levels, for example pH of 6 or above, to release a second pulse of the active ingredient after the first pulse.
  • release of second pulse of active ingredient from the formulation (b) can be time dependent, and the release can further depend upon rate of erosion, diffusion, solubility and/or permeability of the pH-independent layer to intestinal fluids.
  • FIG. 1 shows cross section of one preferred embodiment of formulation (a-1) formulated in accordance with embodiments of the present disclosure.
  • FIG. 2 shows cross section of one preferred embodiment of formulation (b-1) formulated in accordance with embodiments of the present disclosure.
  • the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term "about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable.
  • aspects of the present disclosure relates to modified release oral pharmaceutical composition of dexlansoprazole or pharmaceutically acceptable salts or hydrated forms thereof having a desired drug release profile.
  • the present disclosure provides a dual delayed release pharmaceutical composition of dexlansoprazole or pharmaceutically acceptable salts or hydrated forms thereof.
  • the dual delayed release pharmaceutical composition can incorporate two pulsatile release formulations (a) and (b), wherein formulation (a) can include: (i) a core particle comprising dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof, and (ii) a pH-dependent release-controlled layer; and formulation (b) can include: (i) a core particle comprising dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof, (ii) a pH-independent release -controlled layer, and (iii) a pH-dependent release-controlled layer.
  • distallansoprazole includes the compound dexlansoprazole and its pharmaceutically acceptable salts, polymorphs, solvates and hydrates.
  • delayed release refers to release of dexlansoprazole from an oral pharmaceutical composition, in which dexlansoprazole is released over an extended period of time and/or at a particular location and is taken to encompass prolonged release, timed release, controlled release, retarded release, extended release and sustained release.
  • the core particle can be in the form of an active core particle made of dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof.
  • the core particle may be an inert core particle coated with a layer of dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof.
  • dexlansoprazole may be mixed with an alkaline compound and one or more pharmaceutically acceptable excipients, and the resulting mixture can be formed into an active core.
  • Said active core particles may be produced by extrusion/spheronization, balling or compression utilizing appropriate process equipments. Thus manufactured core materials may be optionally layered with additional pharmaceutical ingredient(s) and active substance(s), and be used for further processing.
  • dexlansoprazole may be mixed with an alkaline compound and one or more pharmaceutically acceptable excipients, and the resulting mixture can be coated on inert seeds to produce core particles.
  • the inert seeds which can be layered with the active substance can include, but not limited to, water insoluble seeds comprising different oxides, celluloses, organic polymers, and water soluble seeds comprising different inorganic salts, sugars, non-pareils.
  • the term "pharmaceutically acceptable excipients” can include, but not limited to, binders, diluents, fillers, disintegrants, basic stabilizers, pore forming substances, gel forming polymers, lubricants, glidants, plasticizers, opacifiers, colouring agents, flavoring agents, solvents and mixtures thereof.
  • Suitable binders can include, but not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, polyvinyl alcohol, Poly vinyl pyrrolidone (PVP), Macrogol, Pullronic F68, gum arabic, polymethacrylates, gelatin, starch and mixtures thereof.
  • HPMC hydroxypropyl methylcellulose
  • PVP Poly vinyl pyrrolidone
  • Macrogol Poly vinyl pyrrolidone
  • Pullronic F68 gum arabic
  • gelatin starch and mixtures thereof.
  • Suitable diluents or fillers can include, but not limited to, microcrystalline cellulose, cellulose, lactose, starch, calcium phosphates, calcium sulphates, mannitol, glucose, sucrose, sorbitol and mixtures thereof.
  • Suitable disintegrants can include, but not limited to, crosslinked carboxymetyl cellulose, sodium starch glycolate, alginic acid and salts, sodium carboxymethyl cellulose, starch, crosslinked polyvinyl pyrrolidone and mixtures thereof.
  • suitable basic stabilizers can include, but not limited to, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, magnesium oxide, calcium oxide, sodium carbonate, potassium carbonate, magnesium carbonate, calcium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium phosphate, magnesium silicate, magnesium aluminate, magnesium metasilicate aluminate, synthetic hydrotalcite, aluminum hydroxide -magnesium, meglumine, lysine, ethylenediamine, ⁇ , ⁇ '-dibenzyl ethylenediamine, procaine, chloroprocaine, choline, diethanolamine and mixtures thereof.
  • suitable pore forming substances can include, but not limited to, mannitol, dextrose, sucrose, lactose, HPMC, HPC, carboxyvinyl polymer, polyethylene glycol 6000, mannitol, an organic acid and mixtures thereof.
  • Suitable gel forming polymers can include, but not limited to, polyethylene oxide (PEO), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC-Na), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose and carboxyvinyl polymer and mixtures thereof.
  • suitable lubricants can include, but not limited to, stearic acid, magnesium, magnesium stearate, calcium or sodium stearate, sodium stearyl fumarate, talc, waxes e.g. carnauba wax, liquid paraffin, glyceryl monostearates, palmitic acid, sodium or magnesium lauryl sulfate, calcium soaps, zinc stearate, polyethylene glycol, sucrose fatty acid ester, polyoxyethylene monostearates, calcium silicate, silicon dioxide, hydrogenated vegetable oils and fats and mixtures thereof.
  • stearic acid e.g. carnauba wax, liquid paraffin, glyceryl monostearates, palmitic acid, sodium or magnesium lauryl sulfate, calcium soaps, zinc stearate, polyethylene glycol, sucrose fatty acid ester, polyoxyethylene monostearates, calcium silicate, silicon dioxide, hydrogenated vegetable oils and fats and mixtures thereof.
  • Suitable glidants can include, but not limited to, talc, aluminium silicate, colloidal silicon dioxide, starch and mixtures thereof.
  • plasticizers can include, but not limited to, polyethylene glycol, dibutyl sebacate, diethyl phthalate, dibutyl phthalate, triacetin, triethyl citrate, acetylated monoglyceride, castor oil and mixtures thereof.
  • Suitable opacifiers can include, but not limited to, titanium dioxide, iron oxide, zinc oxide, and mixtures thereof.
  • suitable colouring agents can include, but not limited to, Food, Drug & Cosmetic (FD&C) dyes such as FD&C blue, FD&C green, FD&C red, FD&C yellow and FD&C lakes; indigo Drug & Cosmetic (D&C) blue, indigotine FD&C blue, carmoisine indigotine (indigo Carmine); iron oxides such as iron oxide red, yellow, black; quinoline yellow, flaming red, carmine, carmoisine, sunset yellow and mixtures thereof.
  • FD&C Food, Drug & Cosmetic
  • D&C indigo Drug & Cosmetic
  • D&C indigotine FD&C blue
  • carmoisine indigotine indigotine
  • iron oxides such as iron oxide red, yellow, black
  • quinoline yellow quinoline yellow, flaming red, carmine, carmoisine, sunset yellow and mixtures thereof.
  • flavouring agents can include, but not limited to, menthol, peppermint, cinnamon, chocolate, vanillin or fruit essences such as cherry, orange, strawberry, grape, black currant, raspberry, banana, red fruits, wild berries and mixtures thereof.
  • the pH-independent release-controlled layer can be formed of a hydrophilic polymer that can be selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose (HPC), carboxyvinyl polymer, polyethylene glycol 6000, lactose, mannitol, pullulan, agar, gellan gum, guar gum, carageenan, acacia gum, gum arabic, dextran, pectin and mixtures thereof.
  • HPMC hydroxypropyl methylcellulose
  • HPC hydroxypropylcellulose
  • the pH-independent release-controlled layer can be formed of a hydrophobic polymer that can be selected from the group consisting of ethyl cellulose, Eudragit® RL, Eudragit® RS, hydrogenated vegetable oils, glyceryl behenate, wax, fatty acid, fatty alcohol, shellac and mixtures thereof.
  • the pH-dependent release-controlled layer can be formed of an enteric coating polymer that can be selected from the group consisting of cellulose acetate trimellitate, methacrylic acid, methyl methacrylate copolymer, cellulose acetate phthalate, cellulose acetate succinate, hydroxypropyl cellulose phthalate, hydroxypropyl ethyl cellulose phthalate, hydroxyl propyl methyl cellulose phthalate, hydroxyl propyl methyl cellulose acetate succinate, hydroxyethyl cellulose phthalate, methylcellulose phthalate, polyvinyl acetate phthalate, polyvinyl acetate hydrogen phthalate, amylase acetate phthalate, cellulose ester phthalates, cellulose ether phthalates, sodium cellulose acetate phthalate, starch acid phthalate, cellulose acetate butyrate, cellulose acetate maleate, cellulose acetate propionate, styrene maleic
  • the two pulsatile release formulations (a) and (b) can be formulated in the form of pellets, tablets, granules, or fine granules, most preferably in the form of pellets.
  • the dual delayed release pharmaceutical composition of dexlansoprazole can be produced in the form of tablet or capsule.
  • the two pulsatile release formulations (a) and (b) can be produced in the form of pellets, which in turn can be filled into a capsule.
  • the pellets can be mixed with one or more excipients and compressed into a multiple unit tablet dosage form.
  • the present disclosure provides a dual delayed release oral pharmaceutical composition of dexlansoprazole, wherein the composition can include: formulation (a-1) comprising a pellet, a tablet, a granule, or a fine granule in which release of dexlansoprazole is controlled; wherein the pellet, tablet, granule, or the fine granule comprising:
  • a core particle comprising dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof;
  • formulation (b-1) comprising a pellet, a tablet, a granule, or a fine granule in which release of dexlansoprazole is controlled; wherein the pellet, tablet, granule, or the fine granule comprising:
  • a core particle comprising dexlansoprazole or a pharmaceutically acceptable salt or a hydrate thereof;
  • the core particle of formulation (a-1) and (b-1) may be coated with a seal coat prior to the application of the delayed release coating.
  • the seal coat layer may be produced using one or more film forming polymers including, but not limited to, hydroxypropyl methylcellulose, hydroxypropyl cellulose, lowsubstituted hydroxypropyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, methyl and ethyl cellulose, PVP/vinyl acetate copolymers, PV A/PEG copolymers and alike.
  • FIG. 1 shows cross section of formulation (a-1) formulated in accordance with embodiments of the present disclosure.
  • Formulation (a-1) can include an inner inert seed that can be coated with a drug layer.
  • the drug layer can include dexlansoprazole and one or more pharmaceutically acceptable excipients.
  • a seal coat layer can be coated on the drug layer before application of the delayed release coating.
  • a pH- dependent release-controlled layer can then be coated on the seal coat layer to provide formulation (a-1) in the form of pellets, tablets, granules, or fine granules.
  • formulation (b-1) can include an inner inert seed, a drug layer surrounding the inert seed, a seal coat layer surrounding the drug layer, a pH-independent release-controlled layer on the seal coat layer and a pH-dependent release-controlled layer.
  • the pH-dependent release-controlled layer of formulation (a-1) can dissolve at a pH ranging from 4.5 to 6 to release a first pulse of the active ingredient.
  • the pH-independent release-controlled layer of formulation (b-1) can dissolve at higher pH levels, for example a pH of 6 or above, to release a second pulse of the active ingredient after the first pulse.
  • release of second pulse of active ingredient from the formulation (b-1) can be time dependent, and the release can further depend upon rate of erosion, diffusion, solubility and/or permeability of the pH-independent release-controlled layer to intestinal fluids.
  • the pH-dependent release-controlled layer of formulation (a-1) and (b-1) can be soluble at a pH ranging from 4.5 to 6, preferably at a pH of 5.5.
  • the modified release oral pharmaceutical composition can release the active ingredient in two pulses i.e. a first pulse of the active ingredient upon administration of the composition to an individual and a second pulse following entry of the composition into the higher pH environment of the intestines.
  • Step IV Enteric coating (Part IB)
  • Step VI Pellets Filling
  • part I and Part II pellets For filling into capsule mix both part I and Part II pellets. Fill into empty shell 150mg pellets for 30mg dose and 300mg pellets for 60mg dose.
  • Step IV Enteric coating (Part IB)
  • Step VI Pellets Filling
  • part I and Part II pellets For filling into capsule mix both part I and Part II pellets. Fill into empty shell 150mg pellets for 30mg dose and 300mg pellets for 60mg dose.
  • Step IV Enteric coating (Part IB) a) Coat enteric coated pellets from stage III with following solution.
  • Step VI Pellets Filling
  • part I and Part II pellets For filling into capsule mix both part I and Part II pellets. Fill into empty shell 150mg pellets for 30mg dose and 300mg pellets for 60mg dose.
  • Step IV Enteric coating (Part IB)
  • Step VI Pellets Filling
  • part I and Part II pellets For filling into capsule mix both part I and Part II pellets. Fill into empty shell 150mg pellets for 30mg dose and 300mg pellets for 60mg dose.

Landscapes

  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition pharmaceutique orale à double libération retardée de dexlansoprazole ou de formes hydratées ou de sels de qualité pharmaceutique de celle-ci. La composition pharmaceutique à double libération retardée selon la présente invention peut comporter deux compositions à libération pulsatile (a) et (b), dans laquelle la composition (a) peut comprendre : (i) une particule noyau comprenant de la dexlansoprazole ou un hydrate ou un sel de qualité pharmaceutique de celle-ci et (ii) une couche à libération contrôlée dépendante du pH ; et la composition (b) peut comprendre : (i) une particule noyau comprenant de la dexlansoprazole ou un hydrate ou un sel de qualité pharmaceutique de celle-ci, (ii) une couche à libération contrôlée indépendante du pH et (iii) une couche à libération contrôlée dépendante du pH.
EP16829940.2A 2015-07-28 2016-07-27 Nouvelle composition orale à double libération retardée de dexlansoprazole Withdrawn EP3328364A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2851MU2015 2015-07-28
PCT/IB2016/054467 WO2017017615A1 (fr) 2015-07-28 2016-07-27 Nouvelle composition orale à double libération retardée de dexlansoprazole

Publications (2)

Publication Number Publication Date
EP3328364A1 true EP3328364A1 (fr) 2018-06-06
EP3328364A4 EP3328364A4 (fr) 2019-01-02

Family

ID=57884420

Family Applications (1)

Application Number Title Priority Date Filing Date
EP16829940.2A Withdrawn EP3328364A4 (fr) 2015-07-28 2016-07-27 Nouvelle composition orale à double libération retardée de dexlansoprazole

Country Status (6)

Country Link
EP (1) EP3328364A4 (fr)
BR (1) BR112018001539A2 (fr)
CL (1) CL2018000220A1 (fr)
CO (1) CO2018002046A2 (fr)
PE (1) PE20181012A1 (fr)
WO (1) WO2017017615A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102727681B1 (ko) * 2019-02-08 2024-11-07 주식회사유한양행 덱스란소프라졸 또는 이의 약학적으로 허용 가능한 염을 함유하는 안정한 경구투여용 약학 제제
CN111991367A (zh) * 2020-09-21 2020-11-27 青岛吉达巴尔国际贸易有限公司 一种埃索美拉唑镁脉冲微丸胶囊剂及制备方法
KR102471545B1 (ko) * 2020-11-20 2022-11-29 서울대학교 산학협력단 덱스란소프라졸을 유효성분으로 포함하는 pH 의존성 타블렛-인-캡슐 복합제제 및 이의 제조방법

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010117756A2 (fr) * 2009-03-31 2010-10-14 Dr. Reddy's Laboratories Ltd Formulations pharmaceutiques de benzimidazole substitué
US20120058194A1 (en) * 2010-08-27 2012-03-08 Navin Vaya Pharmaceutical formulations comprising substituted benzimidazole derivatives
WO2013111149A1 (fr) * 2011-12-21 2013-08-01 Hetero Research Foundation Compositions orales solides à libération contrôlée de dexlansoprazole

Also Published As

Publication number Publication date
PE20181012A1 (es) 2018-06-26
EP3328364A4 (fr) 2019-01-02
CL2018000220A1 (es) 2018-07-20
WO2017017615A1 (fr) 2017-02-02
BR112018001539A2 (pt) 2018-09-18
CO2018002046A2 (es) 2018-02-28

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