WO2010150144A2 - Composition pharmaceutique à dose réduite de célécoxib - Google Patents

Composition pharmaceutique à dose réduite de célécoxib Download PDF

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Publication number
WO2010150144A2
WO2010150144A2 PCT/IB2010/052722 IB2010052722W WO2010150144A2 WO 2010150144 A2 WO2010150144 A2 WO 2010150144A2 IB 2010052722 W IB2010052722 W IB 2010052722W WO 2010150144 A2 WO2010150144 A2 WO 2010150144A2
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WO
WIPO (PCT)
Prior art keywords
celecoxib
salts
self
drug delivery
delivery system
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PCT/IB2010/052722
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English (en)
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WO2010150144A3 (fr
Inventor
Sanjay Mate
Ritesh Kapoor
Munish Talwar
Girish Kumar Jain
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Wockhardt Research Centre
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Publication of WO2010150144A2 publication Critical patent/WO2010150144A2/fr
Publication of WO2010150144A3 publication Critical patent/WO2010150144A3/fr

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Classifications

    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • 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
    • A61K9/4858—Organic 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
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

Definitions

  • composition of the present invention may exhibit improved bioavailability along with reduced undesirable side effects.
  • the invention also relates to processes for the preparation of such compositions.
  • celecoxib is 4-[5-(4-methylphenyl)-3- (trifluoromethyl)-1 H-pyrazol-1 - yl] benzenesulfonamide having a structure of Formula I.
  • Celecoxib is used particularly in the treatment of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, acute pain, primary dysmenorrhea and familial adenomatous polyposis.
  • Celecoxib is a nonsteroidal antiinflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic activity. It is marketed by GD Searle under the trade name Celebrex ® .
  • Celebrex ® is available in 50 mg, 100mg, 200 mg and 400 mg strengths as an immediate- release capsule dosage form.
  • U.S. Patent No. 5,563,165 discloses a pharmaceutical composition comprising a therapeutically-effective amount of celecoxib and a pharmaceutically-acceptable carrier or diluent.
  • U.S. Patent No. 5,972,986 and 6,469,040 disclose the use of cyclooxygenase-2 inhibitors or derivatives thereof in preventing and treating neoplasia.
  • U.S. Patent No. 7,172,769 discloses pharmaceutical compositions comprising one or more orally deliverable dose units, each comprising a selective cyclooxygenase-2 inhibitory drug.
  • U.S. Patent No. 7,220,867 discloses a process for preparing a celecoxib drug substance.
  • U.S. Patent No. 6,589,557 discloses a method for making a porous matrix of celecoxib.
  • U.S. Patent Nos. 6,451 ,339 and 6,383,471 disclose compositions and methods for improved delivery of hydrophobic agents.
  • U.S. Application No. 20060068007 discloses novel class of surfactant-like material that promotes the solubility of poorly soluble compounds.
  • U.S. Application No. 20050079138 discloses a methods for preparing pharmaceutical formulations comprising microparticles with improved dispersibility, suspendability or wettability.
  • U.S. Application No. 20030035833 discloses a rapidly dispersing pharmaceutical composition.
  • PCT Publication WO2009063367 discloses dosage forms comprising celecoxib providing both rapid and sustained pain relief.
  • PCT Publication WO2003043602 discloses solid dispersions containing substituted cyclodextrin and insoluble drug and their preparations.
  • PCT Publication WO2008110534 discloses pharmaceutical compositions of poorly soluble drugs.
  • PCT Publication WO2008065504 discloses multiparticulates of spray-coated drug and polymer on a meltable core.
  • U. S. Application No. 20050191343 discloses reverse micellar formulations for the delivery of hydrophobic or lipophilic compounds, particularly therapeutic compounds.
  • PCT Publication WO2008077823 discloses self-microemulsifying drug delivery systems and microemulsions used to enhance the solubility of pharmaceutical ingredients comprising a polyoxyethylene sorbitan fatty acid ester emulsifier; a fatty acid ester co-emulsifier and oil.
  • PCT Publication WO2008113177 discloses various compounds and compositions comprising polyunsaturated fatty acid monoglycerides and derivatives thereof.
  • Celecoxib is a hydrophobic and highly permeable drug belonging to class Il of biopharmaceutics classification system. Reduced aqueous solubility of celecoxib leads to high variability in absorption and hence has dissolution rate limited bioavailability after oral administration. It also has pre-systemic metabolism. Peak plasma levels of celecoxib occur approximately 3 hrs after an oral dose. Cohesiveness, reduced bulk density and compressibility, and poor reduced properties of celecoxib impart complications in it's processing into conventional solid dosage forms.
  • Celecoxib belongs to the class of COX Il inhibitors.
  • Cox Il inhibitors are under USFDA scanner as these are associated with an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke. This risk may increase with duration of use and with higher dosage. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
  • Cox Il inhibitors have also been reported to be associated with increased gastrointestinal risk. Cox Il inhibitors cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal (Gl) events. Therefore there is a great need to develop a composition with reduced dose and improved bioavailability of celecoxib as reduction in dose ultimately results in reduced side effects.
  • the present inventors while working on the celecoxib composition have surprisingly found that when celecoxib is formulated according to present invention, the resulting compositions have improved solubility, improved dissolution rate, ultimately significant increase in bioavailability and faster onset of action.
  • the increased bioavailability may further lead to reduction in dose, size of dosage form and side effects such as diarrhea, dyspepsia and headache as compared to Celebrex ® (Marketed formulation of celecoxib).
  • celecoxib in an aspect of the invention there is provided a pharmaceutical composition of celecoxib or salts thereof, wherein celecoxib is present in an amount that reduces the side effects associated with high dose compositions of celecoxib.
  • celecoxib composition is in the form of solid dispersion, self-emulsifying drug delivery system or supersaturable self- emulsifying drug delivery system (s-SEDDS).
  • a reduced dose pharmaceutical composition comprising celecoxib or salts thereof wherein the dose of the celecoxib is 120-185 mg.
  • a reduced dose supersaturable self-emulsifying drug delivery system composition comprising 120 to 185 mg of celecoxib or salts thereof, wherein one or both of the rate and extent of absorption of the celecoxib or salts thereof is equal or greater than that obtained by a 200 mg celecoxib formulation marketed under the trade name Celebrex ®
  • Celecoxib is a hydrophobic and highly permeable drug belonging to class Il of biopharmaceutics classification system. Reduced aqueous solubility of celecoxib leads to high variability in absorption and hence has dissolution rate limited bioavailability after oral administration. Further, celecoxibs are associated with an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke. This risk may increase with duration of use and with higher dosage.
  • present invention provided a pharmaceutical composition of celecoxib or salts thereof, wherein celecoxib is present in an amount that reduces the side effects associated with high dose compositions of celecoxib.
  • present invention provided a pharmaceutical composition of celecoxib or salts thereof, wherein composition is in the form of solid dispersion, self- emulsifying drug delivery system or supersaturable self-emulsifying drug delivery system (s-SEDDS).
  • composition is in the form of solid dispersion, self- emulsifying drug delivery system or supersaturable self-emulsifying drug delivery system (s-SEDDS).
  • the present invention further provides a solid dispersion of celecoxib is prepared by dissolving celecoxib with mixtures of solubilizers, alkalizers in suitable solvent system, which is then spray dried.
  • Self-emulsifying drug delivery system is known technique, but it is difficult to predict as for which drugs it will work. As there are various drug related factors which vary from drug to drug and hence influence its improvement in bioavailability like pKa, solubility profile both in oil and water, stability aspects in different media. Non-availability of many products in market based on this technique in spite of being known in art, it indicates that the selection of a drug with this technique and specific set of emulsifiers and oils is highly unpredictable.
  • present invention provides a self emulsifying drug delivery system comprising celecoxib, mixed with mixtures of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle stirring.
  • Self- emulsifying drug delivery system includes self-microemulsifying drug delivery systems (SMEDDS) and selfemulsifying oil formulations (SEOF). In general, these terms are interchangeable.
  • the inventors of present invention have found while working on the celecoxib composition, that when celecoxib is formulated in self-emulsifying drug delivery system; it results in significant increase in solubility of celecoxib.
  • the high surfactant level typically present in self-emulsifying drug delivery system leads to gastrointestinal side effects as well as a reduction in the free drug concentration and thus a reduced rate of intestinal absorption. Therefore, the present invention further provides a supersaturable self-emulsifying drug delivery system (s-SEDDS) in an attempt to reduce the surfactant side effects and achieve rapid absorption of poorly soluble drugs.
  • the s-SEDDS compositions contain a reduced surfactant level as compared to conventional SEDDS system, hence leading to reduced Gl side effects.
  • the supersaturable self-emulsifying drug delivery system comprises polymers in pharmaceutically acceptable vehicle comprising oil and/or emulsifiers, which forms an emulsion on contact with an aqueous environment.
  • the polymers prevent precipitation of the drug by generating and maintaining a supersaturated state in vivo.
  • the system generates a supersaturated solution of the drug when the composition is released from an appropriate dosage form into an aqueous medium.
  • present invention provides a reduced dose solid dispersion composition
  • a reduced dose solid dispersion composition comprising 120 to 185 mg of celecoxib or salts thereof, wherein one or both of the rate and extent of absorption of the celecoxib or salts thereof is equal or greater than that obtained by a 200 mg celecoxib formulation marketed under the trade name Celebrex ® .
  • the present invention also provides a reduced dose self-emulsifying drug delivery system composition
  • a reduced dose self-emulsifying drug delivery system composition comprising 120 to 185 mg of celecoxib or salts thereof, wherein one or both of the rate and extent of absorption of the celecoxib or salts thereof is equal or greater than that obtained by a 200 mg celecoxib formulation marketed under the trade name Celebrex ® .
  • the present invention further provides a reduced dose supersaturable self- emulsifying drug delivery system composition
  • a reduced dose supersaturable self- emulsifying drug delivery system composition comprising 120 to 185 mg of celecoxib or salts thereof, wherein one or both of the rate and extent of absorption of the celecoxib or salts thereof is equal or greater than that obtained by a 200 mg celecoxib formulation marketed under the trade name Celebrex ® .
  • Bioequivalency is established by a 90% Confidence Interval (Cl) of between 0.80 and 1.25 for both C ma ⁇ and AUC under USFDA regulatory guidelines, or a 90% Cl for AUC of between 0.80 to 1.25 and a 90% Cl for C max of between 0.70 to 1.43 under the European EMEA regulatory guidelines.
  • Confidence interval refers to a statistical range with a specified probability that a given parameter lies within the range.
  • compositions of the invention include, (1 ) smaller solid dosage form size; (2) smaller doses of drug required to obtain the same pharmacological effect; (3) increased bioavailability.
  • the solid dispersion composition comprises of pharmaceutically acceptable excipients, wherein excipients comprise one or more of binders, solvents, fillers, alkalizer, lubricants, disintegrants, glidants.
  • Suitable binder may be selected from a group comprising one or more of, povidone, starch, stearic acid, gums, celluloses and the like.
  • Suitable solvents in the process of the present invention are those known to ordinary skilled in the art and include one or more of water, methanol, ethanol, isopropyl alcohol, acetone, methylene chloride and the like.
  • Suitable filler may be selected from a group comprising one or more of, microcrystalline cellulose, calcium phosphate, calcium sulfate, kaolin, dry starch, powdered sugar and the like.
  • Suitable lubricant may be selected from a group comprising one or more of magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate and the like.
  • Suitable glidant may be one or more of colloidal silicon dioxide, talc or cornstarch and the like.
  • Suitable disintegrant may be one or more of starch, croscarmellose sodium, crosspovidone, sodium starch glycolate and the like.
  • Suitable solubilizer comprises polymers selected from one or more of hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), methyl cellulose, hydroxypropylcellulose (HPC), Eudragits, polyvinylpyrrolidone (PVP) and the like. These polymers act as solubilizing agent as they enhance the solubility of drug by increasing its hydrophilicity.
  • Suitable alkalizer may be one or more of a group comprising one or more of amino acid, an amino acid ester, ammonium hydroxide, calcium hydroxide, potassium hydroxide, sodium hydroxide, sodium hydrogen carbonate, aluminum hydroxide, calcium carbonate, potassium carbonate, magnesium carbonate, magnesium hydroxide, methyl glucamine, diethanolamine, tromethamine, magnesium aluminum silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium aluminum hydroxide, diisopropylethylamine, ethanolamine, meglumine, ethylenediamine, triethanolamine, triethylamine, and triisopropanolamine, salts of a pharmaceutically acceptable cation and acetic acid, salts of a pharmaceutically acceptable acid, such as acetic acid, acrylic acid, adipic acid, alginic acid, alkanesulfonic acid, amino acids, ascorbic acid, benzoic acid, boric acid, butyric acid, carbonic acid, citric acid, fatty acids,
  • present invention provides a reduced dose pharmaceutical composition
  • a reduced dose pharmaceutical composition comprising self-emulsifying drug delivery system or saturable self-emulsifying drug delivery system of celecoxib or salts thereof further comprises of pharmaceutically acceptable vehicle optionally with one or more pharmaceutically acceptable excipients, wherein the pharmaceutically acceptable vehicle comprises one or more emulsifiers and/or oil.
  • Suitable emulsifiers are those known to ordinary skill in the art and include one or more of polyoxyethylene glycerol esters of fatty acids, such as Tagats; polooxylated castor oil, ethylene glycol esters, such as glycol stearate and distearate; propylene glycol esters, such as propylene glycol myristate; glyceryl esters of fatty acids, such as glyceryl stearates and monostearates; sorbitan esters, such as spans and tweens; polyglyceryl esters, such as polyglyceryl A- oleate; fatty alcohol ethoxylates, such as Brij type emulsifiers; ethoxylated propoxylated block copolymers, such as poloxamers; polyethylene glycol esters of fatty acids, such as Labrafils, Labrafacs, and Labrasols; cremophores; glycerol monocap
  • Surfactants include hydrophillic and/or lipophilic surfactants.
  • Hydrophilic surfactant is selected from one or more of lauryl macrogoiglycerides; polyethylene glycol fatty acids esters; polyethylene glycol glycerol fatty acid esters; polyoxyethylene sorbitan fatty acid esters; polyoxyethylene- polyoxypropylene block copolymers; polyglycerol fatty acid esters; polyoxyethylene glycerides; polyoxyethylene vegetable oils; polyoxyethylene hydrogenated vegetable oils; reaction mixtures of polyols and at least one member of the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols; tocopherol polyethylene glycol succinates; sugar esters; fatty acid derivatives of amino acids, carnitines, oligopeptides, and polypeptides; glyceride derivatives of amino acids, oligopeptides, and polypeptides; acyl lactylates; mono-,di
  • Lipophillic surfactant is selected from one or more of triglycerides; fatty acids; lower alcohol fatty acid esters; polyethylene glycol glycerol fatty acid esters; polypropylene glycol fatty acid esters; polyoxyethylene glycerides; glycerol fatty acid esters; acetylated glycerol fatty acid esters; lactic acid derivatives of mono/diglycerides; sorbitan fatty acid esters; polyoxyethylene sorbitan fatty acid esters; polyoxyethylene-polyoxypropylene block copolymers; polyoxyethylene vegetable oils; polyoxyethylene hydrogenated vegetable oils; and reaction mixtures of polyols and fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils and the like.
  • HLB surfactant like tweens and reduced HLB surfactant like polyethylene glycol esters of fatty acids, such as Labrafils, Labrafacs, and Labrasols is used.
  • Suitable oils are those known to ordinary skill in the art and include but not limited to one or more of Neobee oil; Miglyol derivatives (fractionated coconut oil), soy oil, almond oil, olive oil, peanut oil, other fatty acid esters of glycerols, medium chain triglycerides and the like.
  • the pharmaceutical composition of the invention may include one or more of other auxiliary agents known in the art like antioxidants, sweetener, colorants, flavoring agents, preservatives, chelating agent, antioxidant, taste masking agent and the like.
  • auxiliary agents known in the art like antioxidants, sweetener, colorants, flavoring agents, preservatives, chelating agent, antioxidant, taste masking agent and the like.
  • Suitable sweetener may include one or more of monosaccharides, disaccharides and polysaccharides, e.g. xylose, ribose, glucose, mannose, galactose, fructose, sucrose, maltose, invert sugar, partially hydrolyzed starch, corn syrup solids, mannitol, xylitol, D-sorbitol, erythritol, pentitol, hexitol, malitol, dihydrochalcones, monellin, steviosides or glycyrrhizin; saccharin in free acid form, soluble saccharin salts, e.g.
  • dipeptide based sweeteners such as L-aspartic acid derived sweeteners, e.g. aspartame
  • water-soluble sweeteners derived from naturally occurring water-soluble sweeteners e.g. sucralose
  • protein based sweeteners e.g. thaumatococcus danielli (Thaumatin I and II) and the like.
  • Suitable flavoring agents may include those known to the skilled artisan, such as natural, "natural-like” and artificial flavors. These flavors may be chosen e.g. from synthetic flavor oils, flavoring aromatics, oleo-resins and extracts derived e.g. from plants, leaves, freduceders or fruits and the like.
  • Representative flavors may include one or more of spearmint oil, cinnamon oil, peppermint oil, clove oil, bay oil, thyme oil, cedar leaf oil, oil of nutmeg, oil of sage, oil of bitter almonds, vanilla, chocolate, coffee, cocoa and citrus oil, lemon, orange, cherry, grape, lime or grapefruit, and fruit essences, e.g. apple, pear, peach, strawberry, raspberry, cherry, plum, pineapple or apricot; mints such as peppermint (including menthol, especially levomenthol), aldehydes and esters, e.g.
  • Suitable chelating agent may include one or more of citric acid, maleic acid, succinic acid, tartaric acid, EGTA (ethylene glycol-bis ( (3-aminoethyl ether) tetraacetic acid, or egtazic acid) and EDTA (ethylene diamine tetraacetic acid, or edetic acid).
  • EGTA ethylene glycol-bis ( (3-aminoethyl ether) tetraacetic acid, or egtazic acid
  • EDTA ethylene diamine tetraacetic acid, or edetic acid.
  • Such chelating agents are commercially available in various forms, e. g. , as sodium or potassium salts or as the free acids and the like.
  • Suitable antioxidant may include one or more of tocopherol, tocopherol acetate, vitamin E polyethylene glycol succinate, propyl gallate, butylated hydroxytoluene and butylated hydroxanisole and the like.
  • composition of the invention optionally include usual auxiliaries known in the art such as taste masking agents like acrylic polymers, copolymers of acrylates, celluloses, resins; coloring agents like titanium dioxide, natural food colors, dyes suitable for food, drug and cosmetic applications; preservatives like alpha-tocopherol, citric acid, butylated hydroxytoluene, butylated hydroxyanisole, ascorbic acid, fumaric acid, malic acid, sodium ascorbate or ascorbic acid palmitate and the like.
  • auxiliaries like acrylic polymers, copolymers of acrylates, celluloses, resins
  • coloring agents like titanium dioxide, natural food colors, dyes suitable for food, drug and cosmetic applications
  • preservatives like alpha-tocopherol, citric acid, butylated hydroxytoluene, butylated hydroxyanisole, ascorbic acid, fumaric acid, malic acid, sodium ascorbate or ascorbic acid palmitate and the like.
  • s-SEDDS also contains polymers which inhibit precipitation of drug in super- saturable solutions.
  • the polymers comprise one or more of hydroxypropylmethylcellulose, hydroxy propyl cellulose, hydroxyethylcellulose, polyvinylpyrrolidone, low molecular weight polyethylene glycol, high molecular weight polyethylene glycol, polyvinylpyrrolidone vinyl acetate, Eudragit E 100 and the like.
  • the pharmaceutical composition of the present invention can be present in the form of tablet, capsule, powder, disc, caplet, granules, pellets, granules in capsule, minitablets, minitablets in capsule, pellets in capsule, sachet, orally disintegrating tablet, chewable tablet, effervescent tablet, mouth dissolving film, liquid or semi-solid form, filled into hard gelatin capsules, soft gelatin capsules, HPMC (hydroxypropyl methyl cellulose) capsules and other dosage forms suitable for oral administration.
  • HPMC hydroxypropyl methyl cellulose
  • the tablet may vary in shapes such as oval, round, triangle, almond, peanut, pentagonal, trapezoidal, parallelogram and the like.
  • the granules can be prepared by wet granulation, dry granulation or direct compression method.
  • the composition of the present invention can be formulated by preparing solid dispersion of celecoxib or salts thereof with mixtures of solubilizer, alkalizer in suitable solvent system which is then spray dried, and optionally blending this solid dispersion with suitable excipients and converting into suitable dosage form.
  • the formulation When formulation contacts an aqueous environment, for example in the gastrointestinal tract, the formulation spontaneously forms an emulsion.
  • the composition of the invention can be prepared by processes known in the art like mixing celecoxib with mixtures of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle stirring and are formulated as self-emulsifying drug delivery system.
  • composition of the invention can be prepared by processes known in the art like mixing celecoxib with suitable polymers in pharmaceutically acceptable vehicle comprising oil and/or emulsifiers, which forms an emulsion on contact with an aqueous environment.
  • Table 4 provides the dissolution data for celecoxib capsules prepared as per the formula given in Table 3.
  • USP Type 2 Apparatus rpm 50
  • 1000 ml of 0.1 N HCI at 37 Q C ⁇ 0.5 Q C was used as medium.
  • Table 6 provides the dissolution data for celecoxib capsules prepared as per the formula given in Table 3.
  • USP Type 2 Apparatus rpm 50
  • 1000 ml of 0.1 N HCI at 37 Q C ⁇ 0.5 Q C was used as medium.

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Abstract

Cette invention concerne une composition pharmaceutique à dose réduite comprenant du célécoxib ou ses sels, la dose de célécoxib étant de 120 à 185 mg. La composition de l’invention peut présenter une meilleure biodisponibilité ainsi qu’une réduction des effets secondaires indésirables. L’invention concerne également des procédés de préparation de ces compositions.
PCT/IB2010/052722 2009-06-25 2010-06-17 Composition pharmaceutique à dose réduite de célécoxib WO2010150144A2 (fr)

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IN1505MU2009 2009-06-25
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IN1505/MUM/2009 2009-06-25
IN1509/MUM/2009 2009-06-25
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014123355A1 (fr) * 2013-02-05 2014-08-14 에스케이케미칼 (주) Composition de célécoxib administrée par voie orale
WO2014205226A1 (fr) * 2013-06-19 2014-12-24 Kashiv Pharma, Llc Auto-nanoémulsion de médicaments faiblement solubles
WO2016191744A1 (fr) * 2015-05-28 2016-12-01 Dr. Reddy's Laboratories Ltd. Composition orale de célécoxib pour le traitement de la douleur
WO2017208069A3 (fr) * 2016-05-27 2018-01-18 Dr. Reddy's Laboratories Ltd. Composition de célécoxib à usage oral pour le traitement de la douleur
CN113750043A (zh) * 2021-09-18 2021-12-07 山东省药学科学院 一种塞来昔布自乳化口服液及其制备方法
KR20230061942A (ko) * 2021-10-29 2023-05-09 단국대학교 천안캠퍼스 산학협력단 알칼리화제를 포함하는 셀레콕시브 함유 고체분산체 및 이의 제조방법
RU2795918C1 (ru) * 2015-05-28 2023-05-15 Др. Редди'С Лабораториз Лтд. Пероральная композиция целекоксиба для лечения боли

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US9572819B2 (en) 2015-05-28 2017-02-21 Dr. Reddy's Laboratories, Ltd. Oral composition of celecoxib for treatment of pain
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US10376527B2 (en) 2015-05-28 2019-08-13 Dr. Reddy's Laboratories Ltd. Oral composition of celecoxib for treatment of pain
RU2708254C2 (ru) * 2015-05-28 2019-12-05 Др. Редди'С Лабораториз Лтд. Пероральная композиция целекоксиба для лечения боли
RU2795918C1 (ru) * 2015-05-28 2023-05-15 Др. Редди'С Лабораториз Лтд. Пероральная композиция целекоксиба для лечения боли
US10799517B2 (en) 2015-05-28 2020-10-13 Dr. Reddy's Laboratories Ltd Oral composition of celecoxib for treatment of pain
CN114209707A (zh) * 2015-05-28 2022-03-22 瑞迪博士实验室有限公司 用于治疗疼痛的塞来昔布口服组合物
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RU2745196C2 (ru) * 2016-05-27 2021-03-22 Др. Редди'С Лабораторис Лтд. Пероральная композиция целекоксиба для лечения боли
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US10722456B2 (en) 2016-05-27 2020-07-28 Dr. Reddy's Laboratories Ltd Oral composition of celecoxib for treatment of pain
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