WO2016170401A1 - Nouvelle composition injectable de diclofénac sodique - Google Patents

Nouvelle composition injectable de diclofénac sodique Download PDF

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Publication number
WO2016170401A1
WO2016170401A1 PCT/IB2015/054893 IB2015054893W WO2016170401A1 WO 2016170401 A1 WO2016170401 A1 WO 2016170401A1 IB 2015054893 W IB2015054893 W IB 2015054893W WO 2016170401 A1 WO2016170401 A1 WO 2016170401A1
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Prior art keywords
diclofenac
water
amount ranging
sodium
injection
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PCT/IB2015/054893
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English (en)
Inventor
Manish Umed DOSHI
Arunava Anil GHOSH
Siddharth Ramdas MATE
Govind Kondabarao MANE
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UMEDICA LABORATORIES PVT Ltd
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UMEDICA LABORATORIES PVT Ltd
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    • 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
    • A61K9/08—Solutions
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Definitions

  • the present invention relates to injectable preparation of diclofenac and water solubles salts thereof which can be administered via intradeltoid route along with intragluteal, subcutaneous and slow intravenous route.
  • the invention further provides a process of preparing said preparation and its use in treatment of acute or chronic pain & inflammatory conditions.
  • Diclofenac belongs to a class of non-steroidal anti -inflammatory drugs (NSAIDs) with antipyretic and analgesic properties. NSAIDs are usually indicated for the treatment of acute or chronic pain and inflammatory conditions. Similar to other NSAIDS, diclofenac is generally indicated for rheumatoid arthritis, osteoarthritis, Dysmenorrhea (menstrual pain), Headache and migraine, Postoperative pain and also for mild to moderate pain after tissue injury. It has also been used in some countries for the management of actinic keratosis and fever. Eye drops of Diclofenac Sodium are used for the prevention of intra-operative miosis during cataract extraction, for the treatment of inflammation after surgery or accidental trauma, and for the relief of ocular signs and symptoms of seasonal allergic conjunctivitis.
  • NSAIDs non-steroidal anti -inflammatory drugs
  • Diclofenac can be administered by oral as well as by parenteral route. Oral doses of diclofenac range from 100-200mg/day while parenteral doses range from 75 to 150mg/day.
  • Diclofenac Sodium Modified-release preparations of Diclofenac Sodium are available for oral use.
  • Diclofenac has also been given in equivalent oral doses as the free acid in tablet forms as dispersible preparations for short-term treatment up to 3 months period.
  • Diclofenac is also given orally as the potassium salt.
  • Diclofenac Sodium may also be given by deep intramuscular injection into the gluteal muscle in a dose of 75 mg once daily or, if required in severe conditions, 75 mg twice daily.
  • Diclofenac Sodium may also be given as a continuous or intermittent intravenous infusion in glucose. 5% or sodium chloride 0.9% (both previously buffered with sodium bicarbonate) or as a bolus intravenous injection.
  • a dose of 75 mg may be given over 30 to 120 minutes or as a bolus injection. The dose may be repeated once after 4 to 6 hours if necessary.
  • Diclofenac sodium may be given after surgery over 15 to 60 minutes followed by 5 mg / hour to a maximum of 150 mg daily.
  • the initial dose may be given as a bolus injection over 5 to 60 seconds followed by additional injections up to the maximum daily dosage; this may be repeated after 4 to 6 hours if necessary although the total dose should not exceed the maximum daily dose of 150 mg.
  • the maximum period recommended for parenteral use is 2 days.
  • Diclofenac Sodium is also used intramuscularly in renal colic in a dose of 75 mg repeated once after 30 minutes if necessary.
  • Diclofenac injections have to be administered deep intramuscularly and are generally administered intraguluteally as the injection causes substantial pain at the site of injection and its administration in the deltoid (upper arm) region is generally avoided.
  • Pain at the site of injection is due to relatively large volume of the injection (3 mL) and the fact that the injection solution contains relatively high volumes of propylene glycol, which is a known irritant upon parenteral administration.
  • the injection solution contains relatively high volumes of propylene glycol, which is a known irritant upon parenteral administration.
  • propylene glycol which is a known irritant upon parenteral administration.
  • intramuscular injection volumes above 2 ml and up to 5 ml must be administered into the gluteal muscle. This is because; the gluteal muscle is larger as compared to the deltoid muscle and hence can accommodate the relatively larger injected volume (3-5 ml). On the other hand if this relatively larger volume is injected into the deltoid muscle, which has relatively lesser muscle mass, the injected solution will cause excessive stretching of the muscle fiber, thereby damaging the local muscle tissue and hence cause pain and discomfort to the patient.
  • VOLTAROL ® ampoules comprise 75mg/3ml solution of Diclofenac sodium which is used as Intra muscular injection.
  • the formulation must be diluted with 100-500ml of either sodium chloride solution (0.9%) or glucose solution (5%) buffered with sodium bicarbonate solution (0.5ml 8.4% or 1ml 4.2%) so that only clear solutions are used as intravenous infusion.
  • sodium metabi sulphite present in solution for injection can also lead to isolated severe hypersensitivity reactions and bronchospasm.
  • DYLOJECT ® 75mg/2ml solution for injection of diclofenac sodium. It can be given as intravenous bolus injection for the treatment or prevention of post-operative pain in supervised healthcare system or as an intramuscular injection for the treatment of acute pain and inflammatory conditions. It cannot be given as IV infusion. It is HP-beta-cyclodextrin complex and contains monothioglycerol as antioxidant. These products Dyloject and Voltarol cause thrombophlebitis in 5.4% and 4.9% patients respectively.
  • Diclofenac sodium soluble and the hyper-osmolar nature of the formulation contribute to the discomfort which is frequently experienced at the site of the injection when administered intramuscularly.
  • injectable Diclofenac preparations contain relatively high amounts (18-40%) of propylene glycol, which is known irritant.
  • US Patent No.3558690 discloses injectable preparations comprising water soluble salts of substituted phenyl acetic acid derivatives (diclofenac being one such compound) in concentrations of 0.5 to 5 %.
  • PCT application number WO 9603121 Al describes a antiphlogistic, analgesic, antipyretic parenteral preparation comprising diclofenac, its salt, or both, a surfactant, co-surfactant, water, at pH of 3-10 and optionally comprising an oily component, that can exhibit sustained therapeutic levels of diclofenac in plasma and which does not cause pain at site of injection.
  • US5389681 discloses to a pharmaceutical composition in the form of a sterilizable parenteral solution comprising a diclofenac salt and stabilizers, such as ethyl lactate combined with glutathione or N- acetylcysteine.
  • the invention describes a method for treating pain, inflammation or rheumatic diseases.
  • US555465 discloses an antiphlogistic, analgesic, antipyretic parenteral preparation comprising diclofenac, its salt, or both, a surfactant, and co-surfactant, and water, and having a pH of 3-10 is provided.
  • EP0658347A2 covers a method of preparing an injectable pharmaceutical or veterinary composition which comprises either diclofenac or a salt thereof and 2-hydroxypropyl beta-cyclodextrin, or an inclusion complex of diclofenac or a salt thereof and 2-hydroxypropyl beta-cyclodextrin, includes the step of dissolving either the diclofenac or salt thereof and the 2-hydroxypropyl beta-cyclodextrin, or the inclusion complex, in water to form a solution, the water having been acidified to a pH such that the pH of the solution is from 6.0 to 8.5 inclusive, in the absence of a phosphate buffer.
  • US2005/0238674 relates to a stable parenteral aqueous solutions comprising either (a) diclofenac or a pharmaceutically acceptable diclofenac salt and a cyclodextrin, or (b) an inclusion complex of diclofenac or a pharmaceutically acceptable diclofenac salt and a cyclodextrin, or a mixture of (a) and (b), which are suitable for intramuscular and intravenous administration.
  • the solutions contain diclofenac or diclofenac salt, cyclodextrin, and an antioxidant selected from monothioglycerol, or a combination of ethylene-diamine tetra-acetic acid and N-acetyl-cysteine.
  • the parenteral solution is in the form of a unit dose that does not exceed 2 milliliters.
  • the stabilized injectable solution of the invention may be intravenously administered by admixture with non-dextrose infusion fluids.
  • US2011/0275717 discloses a pharmaceutical formulation comprising a pharmaceutically acceptable salt of Diclofenac, at least one polyoxyalkylene ester of a hydroxyl fatty acid, water, and, optionally, a co- solvent. This composition has a limitation with use of fatty acid derivative and requires special carriers.
  • US5679660 teaches about the method of preparing an injectable pharmaceutical or veterinary composition which comprises either Diclofenac or a salt thereof and 2-hydroxypropyl beta-cyclodextrin, or an inclusion complex of Diclofenac or a salt thereof and 2-hydroxypropyl beta-cyclodextrin with preferred' concentration of Diclofenac of 25 mg/ml.
  • the volume of injection prepared by this method contains 75mg/3ml Diclofenac which can be painful as IM dosage form.
  • the use of beta cyclodextrin has also toxicity problem which is always questioned for IV administration.
  • US20080153914 discloses injectable formulations of water-soluble salts of diclofenac in Glycofurol.
  • Glycofurol is known as a tissue irritant.
  • US 4,614,741 teaches about the depot injectable containing anti-inflammatory agents like Diclofenac or Diclofenac Sodium, which was prepared in 10-60% of suspending agents selected from the group consisting of biscoleo, isopropyl myristate, ethyl oleate, castor oil, sesame oil, arachis oil, cottonseed oil, almond oil, olive oil, neats foot oil, neutral oil and maize oil, for intramuscular administration.
  • suspending agents selected from the group consisting of biscoleo, isopropyl myristate, ethyl oleate, castor oil, sesame oil, arachis oil, cottonseed oil, almond oil, olive oil, neats foot oil, neutral oil and maize oil, for intramuscular administration.
  • suspending agents selected from the group consisting of biscoleo, isopropyl myristate, ethyl oleate, castor oil, sesame oil, arachis oil, cottonseed
  • US 4,711,906 discloses an aqueous, stable, relatively concentrated solution of Diclofenac, which contain a mixture of propylene glycol and polyethylene glycol in defined quantitative proportions.
  • the solutions preferably contain a local anesthetic such as lidocaine and a reducing agent as stabilizer.
  • a local anesthetic such as lidocaine
  • a reducing agent such as stabilizer.
  • propylene glycol makes the injection painful and lignocaine is added to alleviate such painful administration.
  • the present invention attempts to provide preparations comprising 75mg of water soluble salt of diclofenac & reducing the volume of injection to 1ml resulting in the minimization of pain at site of injection. Further, smaller volume enables administration in the deltoid muscle.
  • It is an objective of invention to provide an injectable composition comprising therapeutically effective amount of diclofenac or water soluble salts thereof, in a solvent system comprising two or more solubilizers and water.
  • Another objective of invention is to provide a therapeutic effective dose of 75mg of water soluble salts of diclofenac in just one ml, without significantly raising the viscosity of the injection preparation.
  • Another objective of invention is to provide a composition comprising diclofenac suitable to be given through multiple routes viz., intramuscular or intravenous or subcutaneous, intradeltoid or intragluteal route of administration.
  • Another objective of invention is to provide patient compliant aqueous composition of diclofenac which is not irritating or painful.
  • Another objective of invention is to provide simple & economical process for the preparation.
  • Still another object of the invention is to provide an economical and physiologically effective composition comprising diclofenac or water soluble salts thereof.
  • the present invention provides an injectable preparation comprising 75mg/ml to 100 mg/ml of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac in a solvent system comprising two or more solublizers in an amount ranging from 0.01 to 40% w/v and water and optionally, one or more antioxidant (s) in an amount ranging from 0.01 to 0.5% w/v and/or one or more buffering agent (s) in an amount ranging from 0.05 to 1.0% w/v, wherein the pH of the preparation is maintained at 8-9.
  • the invention provides an injectable preparation comprising 75 mg/ml of diclofenac sodium in a solvent system comprising hydroxypropyl-beta-cyclodextrin and polysorbate 80 as solublizers and water.
  • the water soluble salts of diclofenac are selected from the group consisting of diclofenac potassium, diclofenac diethyllamine, diclofenac diethanol amine and diclofenac beta-dimethyl aminoethanol.
  • the amount of two or more solublizers in the preparation is between 0.01 to 40% w/v.
  • the solublizers may be selected from, but not limited to hydroxypropyl-beta-cyclodextrin, polysorbate 80, Cremophor EL, glycofurol, benzyl alcohol, polyethylene glycol, Cremophor RH 40 and hydrogenated soy phosphatidylcholine.
  • the amount of antioxidant (s) in the composition is between 0.01 to 0.5% w/v.
  • the antioxidant (s) may be selected from, but not limited to monothioglycerol, sodium bisulphate and sodium metabisulphate.
  • the amount of the buffering agent is between 0.05 to 1.0% w/v.
  • the buffering agent (s) may be selected from, but not limited to potassium dihydrogen phosphate, phosphate buffer and bicarbonate buffer.
  • the solvent system comprises hydroxypropyl-beta-cyclodextrin in an amount ranging from 0.01 to 40% w/v, polysorbate 80 in an amount ranging from 0.10 to 0.5% w/v and water, and potassium dihydrogen phosphate in an amount ranging from 0.05 to 1.0 % w/v.
  • buffering agent s
  • antioxidant antioxidant
  • the invention provides use of composition comprising 75 mg/ml of diclofenac sodium or water soluble salts of diclofenac in a solvent system comprising two or more solublizers 0.01 to 40% w/v and water and optionally, one or more antioxidant (s) 0.10 to 0.5% w/v and/or buffering agent 0.05 to 1.0 % w/v for treatment or prevention of acute or chronic pain and inflammatory conditions selected from rheumatoid arthritis, osteoarthritis, dysmenorrhea (menstrual pain), headache and migraine, postoperative pain and also for mild to moderate pain after tissue injury, ankylosing spondylitis, pain control of total hip replacement arthroplasty, actinic keratosis and fever, accidental trauma.
  • a solvent system comprising two or more solublizers 0.01 to 40% w/v and water and optionally, one or more antioxidant (s) 0.10 to 0.5% w/v and/or buffering agent 0.05 to 1.0 % w/v for treatment or
  • compositions or “formulation” as used herein refers to parenteral preparations include injections, intravenous infusions, powders for injections or intravenous infusions, concentrates for injections or intravenous infusions, implants.
  • buffering agent refers to either a weak acid or weak base. Buffering agents are usually added to water to form a buffer solution, which only slightly changes its pH in response to other acids and bases being combined with it, particularly a strong acid or a strong base.
  • antioxidant refers to substance that inhibits the oxidation of other substances. They are widely used to prevent the oxidative degradation of product.
  • pharmaceutically acceptable is meant those salts and esters which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use.
  • the invention provides a composition comprising Diclofenac or salt thereof.
  • Diclofenac salt is selected from Diclofenac sodium, Diclofenac potassium, Diclofenac diethylamine, Diclofenac diethanolamine or Diclofenac beta-dimethyl aminoethanol. Poor aqueous solubility of the Sodium salt of Diclofenac has a particularly high tendency to crystallize from aqueous and organic solutions.
  • the invention provides therapeutically effective amount of Diclofenac or salts thereof in an aqueous composition suitable to be administered by multiple routes.
  • compositions comprising additional excipients e.g. buffering agents, solubilizers and antioxidants.
  • additional excipients e.g. buffering agents, solubilizers and antioxidants.
  • the composition comprises solubilizers at a concentration in the range of 0.01 to 40%.
  • the Solubilizers include but not limited to hydroxypropylbetadex (Hydroxypropyl-beta- cyclodextrin), polysorbate 80 (Tween 80), Cremophor EL, glycofurol, acetic acid, N[3- hydroxyethyllactamide, benzyl alcohol, polyethylene glycol, Cremophor RH 40, d-alpha-tocopherol polyethylene glycol 1000 succinate, sulfobutylether-beta-cyclodextrin,L-alpha- dimyristoylphosphatidylglycerol, hydrogenated soy phosphatidylcholine.
  • hydroxypropylbetadex Hydroxypropyl-beta- cyclodextrin
  • polysorbate 80 Teween 80
  • Cremophor EL glycofurol
  • acetic acid N[3- hydroxyethyllactamide
  • benzyl alcohol polyethylene glyco
  • the antioxidant includes but not limited to monothioglycerol,thioglycerols, acetyl cysteine, sodium bisulphate, sodium metabisulphate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbates, ascorbylpalmitate, methylparaben, propylparaben, thiomersal and mixed Tocopherol ingredient.
  • the invention provides composition comprising the solvent system consisting of hydroxypropyl-beta-cyclodextrin, 0.01 to 40% w/v, polysorbate 80,0.10 to 0.5% w/v and water, and potassium dihydrogen phosphate, 0.05 to 1.0 % w/v.
  • the invention provides method of use of an injectable composition comprising Diclofenac or water soluble salts thereof 75mg for treatment or prevention of various musculoskeletal and joint disorders like rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, peri-articular disorders like bursitis and tendinitis, soft tissue disorders like sprains and strains, painful condition such as renal colic, acute gout, dysmenorrhoea, migraine and some surgical procedures, in management of actinic keratosis and fever, postoperative pain, juvenile idiopathic arthritis, acute postoperative pain, intra-operative miosis, for treatment of inflammation after surgery, pain control of total hip replacement arthroplasty.
  • Diclofenac or water soluble salts thereof 75mg for treatment or prevention of various musculoskeletal and joint disorders like rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, peri-articular disorders like bursitis and tend
  • the pH is critical for maintaining stability of the Diclofenac injection hence pH is maintained at 8 to 9 using suitable buffering agents and alkalizer.
  • the buffering agents may be selected from, but not limited to alkali metal hydroxides like sodium hydroxide, potassium hydroxide, tri sodium citrate, sodium phosphate salts like monosodium phosphate salt or disodium phosphate salt, potassium phosphate salts like mono or di potassium phosphate salt, sodium acetate, potassium dihydrogen phosphate, phosphate buffer, bicarbonate buffer, Tris buffers or other alkaliser are used for adjusting pH in the desired range.
  • Water is added in the composition in quantity sufficient (q.s.) to make it 0.5 ml or 1 ml or to give different volumes for different strength.
  • the injectable composition may be filled in ampoule and vials after aseptic filtration and flushed under nitrogen blanket.
  • the injections so formed are stable and may diluted further in infusion liquid to obtain the desired strength of drug or without diluting further by intramuscular and as slow bolus intravenous or suitably adding to infusion liquid as per physician need.
  • the invention provides a process for preparing composition comprising 75mg of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac comprising suspending diclofenac sodium or water soluble salt of diclofenac in the solvent system comprising two or more solubilizers in water for injection, with stirring under constant nitrogen purging, optionally, adding said one or more buffering agent (s) and/or antioxidant (s); adjusting pH between 8-9 using an alkali; further diluting with water for injection to achieve concentration of 75mg in 1 ml; sterilizing by sterile filtration and filling in 1 ml ampoules flushed with inert gas prior to sealing.
  • s buffering agent
  • antioxidant antioxidant
  • the invention provides a process for preparing composition comprising 75mg of diclofenac sodium or therapeutically equivalent amounts of water soluble salts of diclofenac comprising suspending diclofenac sodium or water soluble salt of diclofenacin the solvent system comprising hydroxypropyl- beta-cyclodextrin and polysorbate 80 in water for injection, with stirring under constant nitrogen purging, adding potassium dihydrogen phosphate, adjusting pH between 8-9 using an alkali, further diluting with water for injection to achieve concentration of 75mg in 1 ml, sterilizing by sterile filtration and filling in 1 ml ampoules flushed with inert gas prior to sealing.
  • Example 2 Make up the volume to 1 mL with water for injection and stir it. Filter the solution through 0.45 micron membrane filter and then through 0.22 micron membrane filter and again check the pH of filtered solution. Carry out filling of the solutions in clear glass ampoules followed by sealing.
  • Example 2 Make up the volume to 1 mL with water for injection and stir it. Filter the solution through 0.45 micron membrane filter and then through 0.22 micron membrane filter and again check the pH of filtered solution. Carry out filling of the solutions in clear glass ampoules followed by sealing.
  • Example 2 Example 2

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Abstract

La présente invention concerne des préparations injectables contenant 75 mg à 100 mg de sels de diclofénac solubles dans l'eau dans environ 1 ml de solution d'injection, où le pH de la solution est maintenu à 8-9 à l'aide d'alcali. La composition est appropriée pour une administration parentérale par l'intermédiaire des voies intramusculaire, intraveineuse, sous-cutanée, intradeltoïde, intraglutéale. Plus spécifiquement, les préparations injectables comprennent 75 mg/ml de diclofénac sodique dans un système de solvant contenant de l'eau et deux ou plus de deux agents de solubilisation avec des antioxydants et des agents tampons. L'invention concerne également un procédé de préparation de la composition injectable.
PCT/IB2015/054893 2015-04-20 2015-06-30 Nouvelle composition injectable de diclofénac sodique Ceased WO2016170401A1 (fr)

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IN1601MU2015 2015-04-20

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018142313A1 (fr) * 2017-02-02 2018-08-09 Hetero Healthcare Limited Préparations aqueuses pour injection de diclofénac et de ses sels pharmaceutiquement acceptables
US20180271815A1 (en) * 2017-03-24 2018-09-27 Cadila Healthcare Limited Storage stable aqueous injectable solution comprising diclofenac
WO2021048748A1 (fr) 2019-09-09 2021-03-18 Ftf Pharma Private Limited Formulations pharmaceutiques contenant du diclofénac
US11707443B2 (en) 2019-09-26 2023-07-25 Rk Pharma Inc. Storage stable aqueous parenteral solutions comprising diclofenac

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0595766A1 (fr) * 1992-10-22 1994-05-04 Ciba-Geigy Ag Solutions à usage parenteral contenant des sels du diclofenac
CH694034A5 (de) * 2002-12-12 2004-06-30 Mepha Ag Diclofenac-Kalium Injektionslösung.
WO2006126214A2 (fr) * 2005-05-27 2006-11-30 Panacea Biotec Ltd. Nouvelles compositions injectables et procede de preparation desdites compositions
WO2014102824A1 (fr) * 2012-12-28 2014-07-03 Themis Medicare Limited Composition de diclofénac
US8809393B2 (en) * 2005-02-01 2014-08-19 Troikaa Pharmaceuticals Ltd Injectable preparations of diclofenac and its pharmaceutically acceptable salts

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0595766A1 (fr) * 1992-10-22 1994-05-04 Ciba-Geigy Ag Solutions à usage parenteral contenant des sels du diclofenac
CH694034A5 (de) * 2002-12-12 2004-06-30 Mepha Ag Diclofenac-Kalium Injektionslösung.
US8809393B2 (en) * 2005-02-01 2014-08-19 Troikaa Pharmaceuticals Ltd Injectable preparations of diclofenac and its pharmaceutically acceptable salts
WO2006126214A2 (fr) * 2005-05-27 2006-11-30 Panacea Biotec Ltd. Nouvelles compositions injectables et procede de preparation desdites compositions
WO2014102824A1 (fr) * 2012-12-28 2014-07-03 Themis Medicare Limited Composition de diclofénac

Cited By (8)

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