WO2017080566A1 - Composition pharmaceutique analgésique stable et son procédé de préparation - Google Patents

Composition pharmaceutique analgésique stable et son procédé de préparation Download PDF

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Publication number
WO2017080566A1
WO2017080566A1 PCT/EP2015/002239 EP2015002239W WO2017080566A1 WO 2017080566 A1 WO2017080566 A1 WO 2017080566A1 EP 2015002239 W EP2015002239 W EP 2015002239W WO 2017080566 A1 WO2017080566 A1 WO 2017080566A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutically acceptable
ibuprofen
derivative
prodrug
agents
Prior art date
Application number
PCT/EP2015/002239
Other languages
English (en)
Inventor
Agni GRYPIOTI
Panagiotis BARMPALEXIS
Original Assignee
Rontis Hellas S.A.
Pharos 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
Application filed by Rontis Hellas S.A., Pharos Ltd. filed Critical Rontis Hellas S.A.
Priority to PCT/EP2015/002239 priority Critical patent/WO2017080566A1/fr
Publication of WO2017080566A1 publication Critical patent/WO2017080566A1/fr

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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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

Definitions

  • the present invention relates to a stable pharmaceutical composition
  • a stable pharmaceutical composition comprising a therapeutically effective quantity of Ibuprofen or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and Hyoscine Butylbromide or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and a process for the preparation thereof.
  • the stable pharmaceutical composition of the present invention is useful as an analgesic agent and in the treatment of spasmodic pain in diseases of the stomach and intestines, cramping pain and dysfunction in the biliary tract, urinary tract and female genital organs, such as dysmenorrhea.
  • Ibuprofen' s chemical name is ( ⁇ )-2-(p-isobutylphenyl) propionic acid, and its chemical structure is presented by the following Formula I.
  • Ibuprofen is a commonly prescribed Non-Steroidal Anti-inflammatory Drug (NSAID). Ibuprofen is indicated for its analgesic and anti-inflammatory effects in the treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's disease), ankylosing spondylitis, osteoarthritis and other non-rheumatoid (seronegative) arthropathies. In the treatment of non- articular rheumatic conditions, is indicated in periarticular conditions such as frozen shoulder (capsulitis), bursitis, tendonitis, tenosynovitis and low back pain.
  • NSAID Non-Steroidal Anti-inflammatory Drug
  • Ibuprofen is also indicated for its analgesic effect in the relief of mild to moderate pain such as dysmenorrhoea, dental and postoperative pain and for symptomatic relief of headache, including migraine headache, while it can also be used in soft tissue injuries such as sprains and strains.
  • Ibuprofen works by blocking enzyme cyclo-oxygenase, which produces prostaglandins that are involved in inflammation and pain.
  • the recommended dose of Ibuprofen in adults is 1200-1800 mg daily in divided doses. Some patients can be maintained on 600-1200 mg daily. In severe or acute conditions, it can be advantageous to increase the dosage until the acute phase is brought under control, provided that the total daily dose does not exceed 2400 mg in divided doses.
  • Ibuprofen is rapidly absorbed from the gastrointestinal tract and metabolized in the liver in two inactive metabolites and said metabolites together with unchanged ibuprofen are excreted by the kidney either as such or as conjugates. Excretion by the kidney is both rapid and complete. Although, Ibuprofen has highly effective pain relieving properties, it may cause abnormal stomach or intestinal bleeding that may sometimes even prove fatal, especially when administered in high dose.
  • Hyoscine Butylbromide also known as Scopolamine butylbromide is an antispasmodic drug indicated for the relief of spasm of the genito-urinary tract or gastro- intestinal tract and for the symptomatic relief of irritable bowel syndrome (IBS). Its chemical name is 7(S)- (la,2 ,4p,5a,7p)]-9-butyl-7-(3-hydroxy-l-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9-azo nitricyclo[3.3.1.0(2,4)]nonanebromide and its chemical structure is presented by the following Formula II.
  • Hyoscine Butylbromide works by relaxing some of the muscles in the gastrointestinal and urinary systems and exerts a spasmolytic action on the smooth muscle of the gastrointestinal, biliary and genito-urinary tracts.
  • hyoscine butylbromide does not enter the central nervous system. Therefore, anticholinergic side effects at the central nervous system do not occur.
  • Peripheral anticholinergic action results from a ganglion-blocking action within the visceral wall as well as from an anti-muscarinic activity.
  • EP-A-2702989 discloses a stable pharmaceutical composition comprising ibuprofen and scopolamine butylbromide with one or more species selected from the group consisting of a xanthine derivative, tranexamic acid or a salt thereof, acetaminophen and an isovaleryl urea derivative.
  • an object of the present invention to provide a pharmaceutical composition for oral administration comprising Ibuprofen or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and Hyoscine Butylbromide or a pharmaceutically acceptable salt, prodrug, or derivative thereof, with enhanced stability which overcomes the deficiencies of the prior art. Still, it is another object of the present invention to provide a pharmaceutical composition for oral administration comprising Ibuprofen or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and Hyoscine Butylbromide or a pharmaceutically acceptable salt, prodrug, or derivative thereof, with better dose and patience compliance.
  • a pharmaceutical composition for oral administration comprising a therapeutically effective quantity of Ibuprofen or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and Hyoscine Butylbromide or a pharmaceutically acceptable salt, prodrug, or derivative thereof, wherein the weight ratio of Hyoscine butylbromide to Ibuprofen is about 1 :20 in order to improve the stability of the composition and provide better dose and patience compliance.
  • the pharmaceutical composition for oral administration further comprises a pharmaceutically acceptable acidifying agent, such as anhydrous citric acid, citric acid hydrate, sodium citrate hydrate, ascorbic acid, tartaric acid, malic acid, succinic acid, gallic acid, acetic acid, lactic acid etc. and/or mixture thereof, from about 0.01 to 50% by weight of the finished dosage form.
  • a pharmaceutically acceptable acidifying agent such as anhydrous citric acid, citric acid hydrate, sodium citrate hydrate, ascorbic acid, tartaric acid, malic acid, succinic acid, gallic acid, acetic acid, lactic acid etc. and/or mixture thereof, from about 0.01 to 50% by weight of the finished dosage form.
  • the present invention provides a process for the preparation of a stable pharmaceutical composition for oral administration comprising a therapeutically effective quantity of Ibuprofen or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and Hyoscine Butylbromide or a pharmaceutically acceptable salt, prodrug, or derivative thereof, wherein the weight ratio of Hyoscine butylbromide to Ibuprofen is about 1 :20 in order to improve the stability of the composition and provide better dose and patience compliance, which process comprises:
  • the term "pharmaceutically acceptable salt” refers to a salt that is not toxic at the specific therapeutic dosage and a salt that does not independently possess significant pharmacological activity.
  • the pharmaceutical composition may be in various forms
  • the preferred solid dosage forms are tablets, capsules and caplets.
  • the improved solid pharmaceutical composition of the present invention is characterized by physicochemical properties suitable for the tablet formulation by wet granulation, dry granulation or dry mixing (compaction), having adequate release rate of the active ingredients and storage stability.
  • the object of the present invention is achieved by employing a therapeutically effective quantity of Ibuprofen or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and Hyoscine Butylbromide or a pharmaceutically acceptable salt, prodrug, or derivative thereof, wherein the weight ratio between Hyoscine butylbromide and Ibuprofen is about 1 :20 in order to improve the stability of the composition.
  • the stability of the pharmaceutical composition containing Hyoscine Butylbromide and Ibuprofen in weight ratio of 1 :20 can be significantly improved when an effective quantity of an acidifying agent is employed as a stabilizer.
  • An acidifying agent has a property of increasing the concentration of hydrogen ion more than hydroxide ion when present in aqueous solution, and thus, represents an excipient that lowers pH of a substance or a solution by increasing the acidity thereof.
  • an acidifying agent according to the present invention may be an excipient which has acidifying effect or increases its acidity, resulting in a pH value of about 7 or lower in an aqueous solution or dispersion.
  • acidifying agent may include, but not limited to, anhydrous citric acid, citric acid hydrate, sodium citrate hydrate, ascorbic acid, tartaric acid, malic acid, succinic acid, gallic acid, acetic acid and lactic acid and mixtures thereof.
  • the acidifying agent is comprised in the pharmaceutical composition of the present invention in an amount from about 0.01 to 50% by weight of the finished dosage form. Said acidifying agent is able to effectively inhibit the chemical and physico-chemical instability of the finished dosage form.
  • an acidifying agent when incorporated in the pharmaceutical composition of the present invention in an amount form about 0.01 to 50% by weight of the finished dosage form, results in a highly stable composition with improved blending, flowing and compression characteristics.
  • composition of the present invention in addition to being highly stable, it demonstrates better dose and patience compliance, as well.
  • the present invention provides a stable pharmaceutical composition for oral administration comprising a therapeutically effective quantity of 400mg Ibuprofen or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and 20mg Hyoscine Butylbromide or a pharmaceutically acceptable salt, prodrug, or derivative thereof, and an effective quantity of an acidifying agent in a quantity from about 0.01 to 50% by weight.
  • the present invention provides a process for the preparation of a stable pharmaceutical composition for oral administration comprising Hyoscine Butylbromide and Ibuprofen in weight ratio of 1 :20, wherein Hyoscine Butylbromide may be incorporated in the composition in intra-granular or extra-granular phase.
  • the pharmaceutical composition of the present invention is an immediate release solid dosage form for oral administration that may be administered four times daily.
  • the pharmaceutical composition of the present invention may be manufactured by wet granulation or dry granulation or dry mixing (compaction) process.
  • Another embodiment of the present invention is the use of wet granulation process for the preparation of solid dosage forms for oral administration such as tablets, capsules and sachets containing Ibuprofen and Hyoscine Butylbromide as active ingredients, which comprises the following steps: a) granulating both active pharmaceutical ingredients (both together or individually) with suitable granulation liquid and at least one pharmaceutically acceptable excipient such as binder, filler or diluent, disintegrant, glidant and/or mixtures thereof, by performing wet or fluid bed granulation; b) drying the obtained granules and sizing through appropriate sieve; c) mixing the granules of step b) for appropriate time with extra-granular excipients; d) lubricating the granules of step c) with suitable lubricants; e) compressing the blend resulting from step d) into tablets, and optionally, coating the tablets.
  • Another embodiment of the present invention is the use of dry granulation process for the preparation of solid dosage forms for oral administration containing Ibuprofen and Hyoscine Butylbromide as active ingredients, which comprises the following steps:
  • step d) granulating both active pharmaceutical ingredients (both together or individually) with at least one pharmaceutically acceptable excipient such as binder, filler or diluent, disintegrant, glidant and/or mixtures thereof by performing roller compaction or by preparing suitable slugs; b) sizing through appropriate sieve; c) mixing the granules of step b) for appropriate time with at least one extra-granular excipient such as binder, filler or diluent, disintegrant, glidant and/or mixtures thereof; d) lubricating the granules of step c) with suitable lubricants; e) compressing the blend resulting from step d) into tablets, and optionally, coating the tablets.
  • pharmaceutically acceptable excipient such as binder, filler or diluent, disintegrant, glidant and/or mixtures thereof by performing roller compaction or by preparing suitable slugs
  • step b) sizing through appropriate sieve;
  • Another embodiment of the present invention is the use of direct compression process for the preparation of solid dosage forms for oral administration containing Ibuprofen and Hyoscine Butylbromide as active ingredients, which comprises the following steps:
  • pharmaceutical acceptable excipient such as binder, filler or diluent, disintegrant, glidant and/or mixtures thereof for appropriate time
  • compositions of the present invention may also contain one or more additional formulation ingredients selected from a wide variety of excipients.
  • any number of ingredients may be selected, alone or in combination, based upon their known uses in preparation of solid oral dosage form compositions.
  • Such ingredients include, but are not limited to, fillers or diluents, binders, compression aids, disintegrants, surfactants, wetting agents, glidants, lubricants, flavours, water scavengers, colorants, sweetener, coating agents and preservatives.
  • compositions or diluents may be selected from starch, microcrystalline cellulose, dicalcium phosphate, lactose monohydrate, calcium carbonate, magnesium carbonate, sorbitol, mannitol, sucrose, dextrine, kaolin, magnesium oxide, calcium sulfate, xylitol, isomalt, glucose, fructose, maltose, acids like citric acid, tartaric acid, fumaric acid, co-polymers such as those from vinyl pyrrolidone and vinyl acetate or those of polyethylene glycol, and mixtures thereof.
  • Preferred diluents are lactose monohydrate and microcrystalline cellulose.
  • binders may be selected povidone, hydroxypropyl methylcellulose, dihydroxy propylcellulose, sodium carboxyl methylcellulose, and mixtures thereof.
  • Pharmaceutically acceptable disintegrants may be selected from sodium starch glycolate, crospovidone, croscarmellose sodium, and/or mixtures thereof. Preferred disintegrant is croscarmellose.
  • Pharmaceutically acceptable lubricants may be selected from magnesium stearate, calcium stearate, stearic acid, stearic acid, glyceryl behenate, hexanedioic acid, hygrogenated vegetable oil sodium stearyl fumarate and glycerine fumarate.
  • Preferred lubricant is magnesium stearate.
  • Pharmaceutical compositions according to the present invention may also comprise glidants such as colloidal silicon dioxide.
  • composition 1 according to the present invention is illustrated in Table 1 below.
  • composition of Example 1 of the present invention were prepared according to the following manufacturing process: a) Pre-Mixing: Weight individuall 400mg Ibuprofen, 20mg Hyoscine Butylbromide and all remaining ingredients 2 to 5, 7 and 8 and pass through appropriate sieve and pre-mix;
  • step b) Granulation/Kneading the blend resulting from step a) is kneaded with purified water until a homogenous mass is produced. The wet mass is passed through appropriate mill;
  • Lubrication weigh individually ingredient 10 and mix with the obtained granules from step d) for appropriate time.
  • step e) the blend resulting from step e) is formulated in a solid dosage form by compression into tablets. Subsequently, the tablets may be coated with appropriate coating material.
  • the produced tablets were tested for content uniformity, disintegration, water content and dissolution proving that they are meeting the specifications.
  • Composition 1 Tablets of Composition 1 were exposed to normal (25°C ⁇ 2°C/60% ⁇ 5% RH), intermediate (30°C ⁇ 2°C/65% ⁇ 5% RH) and accelerated (40°C ⁇ 2°C/75% ⁇ 5% RH) stability studies according to the current ICH guidelines.
  • Example 2 Preparation of Ibuprofen/HyoscineButylbromide 400mg/20mg Tablets
  • a preferred composition 2 according to the present invention is illustrated in Table 2 below.
  • Tablets of composition of Example 2 according to the present invention were prepared according to the following manufacturing process:
  • Pre-Mixing Weight individually 400mg Ibuprofen, 20mg Hyoscine Butylbromide and all the ingredients 2 to 6 and 9 to 14 and pass through appropriate sieve; Subsequently, forming a first homogenous blend by mixing the total quantity of Ibuprofen with the total quantity of ingredients 2 to 6; b) Granulation/Kneading: Kneading the first blend obtained form step a) with purified water and wet granulating by passing the wet mass through appropriate mill; c) Drying: Drying the obtained granules to appropriate Loss of Drying (LOD) and sizing by passing through appropriate sieve; d) Mixing: Mixing for appropriate time the granules from step c) with the total quantity of Hyoscine butylbromide and the extra-granular ingredients 9 to 13; e) Lubrication: mix the blend from step d) for appropriate time with extra-granular ingredient 14; f) Compression: Compress the blend
  • composition 2 of the present invention may optionally be prepared by dry granulation or direct compression.
  • the tablets may be film coated with functional or non-functional coating.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Emergency Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une composition pharmaceutique stable comprenant une quantité thérapeutiquement efficace d'ibuprofène ou d'un sel, promédicament, ou dérivé, pharmaceutiquement acceptable, de celui-ci, et du butylbromure d'hyoscine ou un sel, promédicament, ou dérivé, pharmaceutiquement acceptable, de celui-ci, dans une association à posologie fixe; ainsi que le procédé de préparation de cette composition.
PCT/EP2015/002239 2015-11-09 2015-11-09 Composition pharmaceutique analgésique stable et son procédé de préparation WO2017080566A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/EP2015/002239 WO2017080566A1 (fr) 2015-11-09 2015-11-09 Composition pharmaceutique analgésique stable et son procédé de préparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2015/002239 WO2017080566A1 (fr) 2015-11-09 2015-11-09 Composition pharmaceutique analgésique stable et son procédé de préparation

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WO2017080566A1 true WO2017080566A1 (fr) 2017-05-18

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113490486A (zh) * 2019-02-22 2021-10-08 康特伦英国斯温顿捷迪斯有限公司 最小化团聚、曝气和保持包含布洛芬的药物组合物的包衣

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002045571A2 (fr) * 2000-12-06 2002-06-13 Wyeth Comprime a dissolution rapide
CN101766580A (zh) * 2008-12-29 2010-07-07 北京琥珀光华医药科技开发有限公司 丁溴东莨菪碱布洛芬片及其制备方法
EP2659889A1 (fr) 2010-12-28 2013-11-06 Kowa Co., Ltd. Composition antipyrétique/analgésique
EP2702989A1 (fr) 2011-04-28 2014-03-05 Kowa Company, Ltd. Composition pharmaceutique stable

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002045571A2 (fr) * 2000-12-06 2002-06-13 Wyeth Comprime a dissolution rapide
CN101766580A (zh) * 2008-12-29 2010-07-07 北京琥珀光华医药科技开发有限公司 丁溴东莨菪碱布洛芬片及其制备方法
EP2659889A1 (fr) 2010-12-28 2013-11-06 Kowa Co., Ltd. Composition antipyrétique/analgésique
EP2702989A1 (fr) 2011-04-28 2014-03-05 Kowa Company, Ltd. Composition pharmaceutique stable

Non-Patent Citations (1)

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Title
ANONYMOUS: "Listado de Especialidades Farmaceuticas Registradas Gerencia Sectorial Registro Control (excerpt)", INTERNET CITATION, 23 April 2013 (2013-04-23), XP002759410, Retrieved from the Internet <URL:http://www.inhrr.gob.ve/doc/rc_doc/ef23042013.pdf> [retrieved on 20160628] *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113490486A (zh) * 2019-02-22 2021-10-08 康特伦英国斯温顿捷迪斯有限公司 最小化团聚、曝气和保持包含布洛芬的药物组合物的包衣
US11931464B2 (en) 2019-02-22 2024-03-19 Catalent U.K. Swindon Zydis Limited Minimizing agglomeration, aeration, and preserving the coating of pharmaceutical compositions comprising ibuprofen

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