EP1682096A1 - Procede permettant de preparer des compositions de clopidogrel - Google Patents

Procede permettant de preparer des compositions de clopidogrel

Info

Publication number
EP1682096A1
EP1682096A1 EP04797570A EP04797570A EP1682096A1 EP 1682096 A1 EP1682096 A1 EP 1682096A1 EP 04797570 A EP04797570 A EP 04797570A EP 04797570 A EP04797570 A EP 04797570A EP 1682096 A1 EP1682096 A1 EP 1682096A1
Authority
EP
European Patent Office
Prior art keywords
clopidogrel
granules
particles
aggregates
composition
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Withdrawn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
EP04797570A
Other languages
German (de)
English (en)
Inventor
Ramaswami Bharatrajan
Pallavi Kharkar
Sunil Flat No 203/204 Building No. 3C ROY
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.)
Sandoz AG
Original Assignee
Sandoz AG
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 Sandoz AG filed Critical Sandoz AG
Publication of EP1682096A1 publication Critical patent/EP1682096A1/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Withdrawn legal-status Critical Current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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—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
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • This invention relates to pharmaceutical compositions comprising clopidogrel and to processes for preparing such compositions.
  • Clopidogrel is a known anti-thrombotic agent which inhibits platelet aggregation. See Merck Index, 12 th Edition, entry 2457. Clopidogrel is administered currently in the form of the biphosphate salt as a film-coated tablet.
  • clopidogrel salts are known to exhibit difficulties in formulation.
  • the present applicants have found that clopidogrel in base or salt form, e.g. as mesylate or hydrochloride, is problematic to formulate for example as a tablet, and attribute this principally to hygroscopicity.
  • clopidogrel tablets suffer from degradation on storage.
  • this invention provides a composition suitable for oral administration comprising clopidogrel in base or pharmaceutically acceptable salt form which composition comprises a polymer coating.
  • the polymer coating may comprise a polyvinyl acetate or a polyvinyl alcohol.
  • clopidogrel when in salt form clopidogrel may be selected from mesylate, hydroiodide, hydrobromide and hydrochloride.
  • this invention provides a composition suitable for oral administration comprising clopidogrel in base or pharmaceutically acceptable salt form which composition comprises a hydrophobic component.
  • Suitable hydrophobic components include hydrogenated vegetable oils.
  • the hydrophobic component-containing compositions of this invention may comprise a polymer coating, e.g. a polyvinyl acetate or a polyvinyl alcohol.
  • a polymer coating e.g. a polyvinyl acetate or a polyvinyl alcohol.
  • the hydrophobic component when present, is not coated.
  • this invention provides clopidogrel in form of coated particles, granules or agglomerates.
  • this invention provides a composition suitable for oral administration comprising clopidogrel in base or pharmaceutically acceptable salt form wherein the clopidogrel is in the form of coated particles, granules or agglomerates.
  • this invention provides a composition suitable for oral administration comprising clopidogrel in pharmaceutically acceptable salt form which composition comprises
  • a polymer coating selected from a polyvinyl acetate or a polyvinyl alcohol
  • hydrophobic component comprising a hydrogenated vegetable oil, wherein the salt is selected from mesylate, hydrobromide, hydroiodide and hydrochloride, and wherein the clopidogrel is in the form of coated particles, granules or agglomerates.
  • the particle-, granule- or agglomerate-coating may comprise a hydrophobic polymer, e.g. a polyvinyl acetate or a polyvinyl alcohol, a hydrogenated vegetable oil or a cyclodextrin.
  • a hydrophobic polymer e.g. a polyvinyl acetate or a polyvinyl alcohol, a hydrogenated vegetable oil or a cyclodextrin.
  • Preferred polymer coatings employed in the compositions of this invention are selected from celluose acetate, polymethacrylates for example Eudragit E or Eudragit NE 30 D, and ethylcellulose.
  • Suitable vegetable oils include hydrogenated cottonseed oil e.g. those available commercially as Lubritab or Sterotex; hydrogenated palm oil, e.g. available as Softisan 154 or Dynasan P60; hydrogenated soyabean oil such as that available as Sterotex HM.
  • the hydrophobic component may be selected from cetyl alcohol, cetostearyl alcohol, cholesterol, gyceryl monostearate, glyceryl monooleate, glyceryl palmitostearate and stearic acid.
  • the cyclodextrin may comprise an alpha-, beta- or gamma-cyclodextrin.
  • compositions of this invention herein described may be administered in form of a tablet, sachet, or hard or soft gelatine capsule. Coated tablets are preferred.
  • the clopidogrel may be present in an amount of up to 50% by weight, for example 10 to 45%, e.g. 20 to 40%, e.g. 25 to 35% by weight, based on the total weight of the composition.
  • compositions of this invention may include:
  • Lactose DCL 11 is a suitable grade in the compositions of this invention.
  • microcrystalline cellulose in an amount when present of up to 40% by weight, for example 5 to 35%, e.g. 8 to 25%, e.g. 10 to 20% by weight based on the total weight of the composition.
  • Avicel PH 112 is an appropriate grade for use in the compositions of this invention.
  • Starch 1500 LM is an appropriate grade for use in the compositions of this invention;
  • the hydrogenated vegetable oil when present in an amount of up to about 15% by weight, e.g. 1 to 10%, e.g. 2 to 7% by weight, based on the weight of the composition.
  • oils are commercially available for example under the trade mark Sterotex;
  • the polymer coating when present, in an amount of up to about 10 % by weight, e.g. 2 to 8%, e.g. 4 to 6 % by weight, based on the weight of the composition.
  • Such coatings are available commercially for example under the trade mark Opadry AMB;
  • a filler in an amount when present of up to 80% by weight, for example 5 to 75%, e.g. 10 to 65%, e.g. 15 to 50% by weight based on the total weight of the composition.
  • Mannitol and xylitol are examples of suitable fillers in compositions of this invention.
  • Other components may include titanium dioxide, a hydroxypropyl methylcellulose, a hydroxyl propylcellulose and a propylene glycol.
  • compositions of this invention are more straightforward to formulate than hitherto known compositions.
  • the applicants have found that processability of the components in forming, e.g. tablets, is easier than for known processes for making solid clopidogrel compositions.
  • compositions of this invention are storage-stable. Thus no or negligible degradation is observed on storage at ambient conditions over periods of days, weeks and months.
  • the clopidogrel employed in the compositions and processes of this invention may be in racemate form, in form of a partially- or wholly-enriched diastereomer.
  • the clopidogrel may be in form of a pure or substantially pure diastereomer, e.g. > 90% e.g. 93%, 94%, 95% or > 95%, e.g. 96%, 97% or greater diastereomer as determined using known methods.
  • this invention provides a process for preparing tablets comprising clopidogrel in base or pharmaceutically acceptable salt form which process comprises a) compacting the clopidrogrel with anhydrous or substantially anhydrous components so as to form aggregates, b) breaking down the aggregates so as to form granules or particles, c) optionally mixing the granules or particles with at least one further component, and d) compacting or compressing the granules or particles thus formed into tablets.
  • Compaction may be carried out for example using a roller compactor.
  • the desiccant e.g. anhydrous silica
  • the aggregates or granules may be mixed with the aggregates or granules. This improves stability and flow of the processed mixture.
  • a hydrophobic lubricant e.g. hydrogenated vegetable oil, may be added. This provides improved stability over that observed using conventional lubricants.
  • the process may be carried out in a low- or ultra-low humidity environment.
  • step a) may be milled to granules or particles by screening through a comminuting mill, for example an oscillating granulator, quadrocomill or hammer mill.
  • step b) serves to break the aggregates down in size.
  • process step b) may be carried out so as to form granules with a small or negligible proportion of particles.
  • the output from step b) may amount to 80% or more granules by weight in a granule/particle mixture, e.g. 85%, 90%, 95% or greater e.g. 98%, 99% or 100% granules.
  • the solvent medium may comprise an aqueous or organic solvent or mixture of organic solvents.
  • an aqueous medium when employed, this may containing up to 100% by weight water, e.g. 5 to 80%, e.g. 10 to 60% by weight.
  • the thus coated or encapsulated particles or granules may be further processed, for example into tablets using compaction or compression.
  • Coating of the clopidogrel particles may be achieved using a fiuidised bed, e.g. a Wurster, or by water-in-oil or oil-in-water phase separation or coacervation encapsulation methods.
  • coating of the clopidogrel granules or particles may be carried out after process step b) or step c) if present and before step d).
  • hydrophobic polymer may establish an effective moisture barrier around the particles or tablets.
  • Typical dimensions observed using known methods of particles used in this invention range from 50 microns to 150 microns. 75% of the granules of this invention may be in the size range 100 microns to 500 microns, and 75% of the agglomerates of this invention may be in the size range 500 microns to 2000 microns.
  • a preferred aspect of the invention is a clopidogrel composition as herein described in form of a coated particle, granule, agglomerate or tablet, wherein the coating is free of or substantially free of HPMC.
  • Clopidogrel may be administered at a dose of lOmg, 25mg, 50mg, 60 mg, 75mg or lOOmg drug substance based on clopidogrel base, depending on the patient's body weight and other circumstances. This dose may be daily.
  • the tablet weight When administered in tablet form, the tablet weight may be for example 50 mg, lOOmg, 150 mg, 200 mg or 300 mg in total.
  • Clopidogrel base, mesylate and hydroiodide are sourced from the Torrent company.
  • Clopidogrel hydrochloride may be prepared by processes analogous to those disclosed in published patent applications EP 0 281 459 and WO 98/51682.
  • Clopidogrel hydrobromide may be prepared by passing HBr gas through an organic solution of clopidogrel base, e.g. in toluene, at ambient temperature.
  • Clopidogrel hydrobromide salt precipitates and may be filtered and washed, e.g. with an organic solvent such as toluene.
  • the wet cake of the salt may be dried under vacuum at elevated temperature, for example 50 to 80°C, e.g. 70 to 75°C, to provide clopidogrel HBr as an off-white solid.
  • this invention provides a composition or process substantially as herein described with reference to the examples.
  • this invention provides compositions produced using the processes of this invention.
  • the compositions, e.g. tablets, produced by the processes of this invention may be free of or substantially free of HPMC.
  • the components are mixed together, processed using dry roller compaction into aggregates, compacted to granules and formed into tablets. Processing takes place in a low-humidity environment. 1000 tablets are prepared and divided into 10 lots each of 100 tablets. All ten lots are stored at ambient conditions and inspected at daily intervals. No degradation is detected by visual inspection after 10 days. Negligible degradation is observed after two months.
  • Example 1 is repeated using clopidogrel hydroiodide in place of the mesylate, using molar equivalent to 75 mg clopidogrel base. Stable tablets are produced.
  • Example 1 is repeated using clopidogrel hydrochloride in place of the mesylate using molar equivalent to 75 mg clopidogrel base. Stable tablets are produced.
  • the anhydrous components are mixed together, processed in analogous manner to that in Example 1 and formed into tablets.
  • the tablets are coated using Opadry AMB.
  • 1000 tablets are prepared and divided into 10 lots each of 100 tablets. All ten lots are stored at ambient conditions and inspected at daily intervals. No degradation is detected by visual inspection after 10 days. Negligible degradation isobserved after one month.
  • Example 4 is repeated using clopidogrel hydroiodide in place of the mesylate.
  • the molar equivalent to 75 mg clopidogrel base is used. Stable tablets are produced.
  • Example 4 is repeated using clopidogrel hydrochloride (molar equivalent to 75 mg base) in place of the mesylate. Stable tablets are produced.
  • compositions containing mannitol as a filler are prepared in the following Examples 7 and 9 to 12.
  • Composition 7a is a:
  • the clopidogrel salt is blended with mannitol, microcrystalline cellulose and part of the low substituted hydroxypropylcellulose.
  • the blend is compacted using a Fitzpatrick Chilsonator roller compactor.
  • the compacts are then milled into granules by screening through an oscillating granulator comminuting mill.
  • the granules are blended with part of microcrystalline cellulose, low substituted hydroxypropylcellulose, mannitol, PEG 6000 and Sterotex.
  • the blend is compressed into tablets using a Korsch rotary compressor.
  • the tablets are then coated with Opadry AMB in a Hicoater perforated coating pan.
  • compositions 7b and 7c An analogous procedure is used to prepare compositions 7b and 7c.
  • compositions 9a to 9c are prepared in analogous manner to that for 7a.
  • compositions 10a to 10c are prepared in analogous manner to that for 7a. Examples 1a to lie
  • compositions 11a to lie are prepared in analogous manner to 7a above.
  • Examples 12a and 12b clopidogrel HC1 tablets
  • compositions are prepared in analogous manner to that in Example 7a above, with the omission of Opadry AMB coating in the formulation of Example 12b.
  • the tablet composition of Example 12a exhibits enhanced stability over that of Example 12b.
  • the process of this invention serves to provide more stable and robust clopidogrel compositions than hitherto known compositions. This allows economies such as elimination of more expensive packaging materials.
  • the compositions are reproducible, straightforward and economic to manufacture.
  • the invention provides more stable solid oral dosage forms of clopidogrel- mesylate, -hydroiodide and -hydrochloride.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition convenant à une administration par voie orale comprenant du clopidrogel sous forme de sel pharmaceutiquement acceptable. Cette composition comprend un enrobage polymère choisi parmi un acétate polyvinylique ou un alcool polyvinylique, et un composant hydrophobe comprenant une huile végétale hydrogénée ; le sel est choisi dans le groupe comprenant le mesylate, le bromhydrate, l'iodhydrate et le chlorhydrate. Le clopidogrel se présente sous la forme de particules enrobées, de granules enrobées ou d'agglomérats enrobés. Un autre aspect de cette invention concerne un procédé permettant de préparer des comprimés contenant du clopidogrel sous forme de sel pharmaceutiquement acceptable ; ce procédé consiste a) à compacter le clopidogrel avec des composants anhydres ou essentiellement anhydres de manière à former des agrégats, b) à broyer ces agrégats de manière à former des granules ou des particules, c) éventuellement, à mélanger les granules ou les particules avec au moins un composant supplémentaire, et d) à compacter ou à compresser les granules ou les particules ainsi formées afin d'obtenir des comprimés. Le clopidogrel est utilisé sous la forme de mesylate, de bromhydrate, de iodhydrate, ou de chlorhydrate. Le procédé consiste également à mélanger un capteur d'humidité avec les agrégats, les granules ou les particules. Une étape d'enrobage des granules ou particules peut être ajoutée après l'étape b) ou après l'étape c) lorsqu'il y a des granules ou des particules, et avant l'étape d).
EP04797570A 2003-11-03 2004-11-03 Procede permettant de preparer des compositions de clopidogrel Withdrawn EP1682096A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0325603.9A GB0325603D0 (en) 2003-11-03 2003-11-03 Organic compounds
PCT/EP2004/012437 WO2005048992A1 (fr) 2003-11-03 2004-11-03 Procede permettant de preparer des compositions de clopidogrel

Publications (1)

Publication Number Publication Date
EP1682096A1 true EP1682096A1 (fr) 2006-07-26

Family

ID=29725839

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04797570A Withdrawn EP1682096A1 (fr) 2003-11-03 2004-11-03 Procede permettant de preparer des compositions de clopidogrel

Country Status (8)

Country Link
EP (1) EP1682096A1 (fr)
JP (1) JP2007527414A (fr)
CN (1) CN101848705A (fr)
AU (1) AU2004290511A1 (fr)
BR (1) BRPI0416109A (fr)
CA (1) CA2540965A1 (fr)
GB (1) GB0325603D0 (fr)
WO (1) WO2005048992A1 (fr)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005070464A2 (fr) * 2004-01-21 2005-08-04 Biofarma Ilac Sanayi Ve Ticaret A.S. Formulation de comprimes de bisulfate de clopidogrel
EP1756116A1 (fr) * 2004-04-20 2007-02-28 Sanofi-Aventis Formes polymorphes d'hydrobromure d'acetate de methyl(+)-(s)-alpha-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4h), hydrobromure de clopidrogel
BRPI0510008A (pt) 2004-04-20 2007-09-18 Sanofi Aventis sal de clopidogrel e formas polimórficas deste
MX2007010267A (es) * 2005-02-24 2007-09-11 Teva Pharma Base de clopidogrel adecuada para formulacion farmaceutica y preparacion de ella.
DE202005013839U1 (de) * 2005-09-01 2005-10-27 Helm Ag Pharmazeutische Formulierung für Salze monobasischer Säuren mit Clopidogrel
WO2007054968A2 (fr) * 2005-09-20 2007-05-18 Torrent Pahrmaceuticals Limited Compositions pharmaceutiques atypiques de mesylate de clopidogrel
IS2385B (is) * 2006-02-10 2008-07-15 Actavis Group Hf. Klópidógrel bísúlfat lyfjasamsetningar
CZ298349B6 (cs) * 2006-03-09 2007-09-05 Zentiva, A. S Farmaceutická kompozice clopidogrelu hydrogenbromidu
JP2009532462A (ja) * 2006-04-05 2009-09-10 カディラ・ヘルスケア・リミテッド 調節放出クロピドグレル製剤
DK1847259T3 (da) * 2006-04-13 2010-04-12 Riemser Specialty Production Gmbh Polyxamerer som smøremiddel til farmaceutiske sammensætningen indeholdende thieno[3,2-c]pyridin-derivater
DE202006020892U1 (de) 2006-04-13 2010-10-21 Riemser Arzneimittel Ag Partialglyceride als Schmiermittel für pharmazeutische Zusammensetzungen enthaltend Thieno[3,2-c]pyridin-Derivate
WO2007128476A1 (fr) * 2006-05-04 2007-11-15 Sandoz Ag Compositions pharmaceutiques contenant du chlorhydrate de clopidogrel
KR20080055356A (ko) * 2006-12-15 2008-06-19 에스케이케미칼주식회사 보관안정성이 우수한 클로피도그렐 함유 포접 복합체
KR20080055355A (ko) * 2006-12-15 2008-06-19 에스케이케미칼주식회사 보관안정성이 우수한 클로피도그렐 함유 포접 복합체
EP1970054A3 (fr) 2007-03-14 2009-06-03 Ranbaxy Laboratories Limited Comprimés de clopidogrel
WO2008129468A2 (fr) * 2007-04-20 2008-10-30 Wockhardt Research Centre Compositions pharmaceutiques de clopidogrel
ATE530172T1 (de) * 2008-02-26 2011-11-15 Lesvi Laboratorios Sl Pharmazeutische formulierungen mit clopidogrel
EP2107061A1 (fr) 2008-04-02 2009-10-07 Krka Tovarna Zdravil, D.D., Novo Mesto Procédé de préparation de clopidogrel enrichi optiquement
ATE482961T1 (de) 2008-04-25 2010-10-15 Sandoz Ag Hydrogensulfat von 2-acetoxy-5-(a- cyclopropylcarbonyl-2-fluorbenzyl)-4,5,6,7- tetrahydrothienoä3,2-cüpyridin und dessen zubereitung
EP2398468B1 (fr) 2009-02-17 2016-11-30 KRKA, D.D., Novo Mesto Compositions pharmaceutiques comprenant du prasugrel ou ses sels d'addition d'acide pharmaceutiquement acceptables, et leurs procédés de préparation
JP2013032289A (ja) * 2009-10-28 2013-02-14 Daiichi Sankyo Co Ltd ワックス安定製剤
ES2363964B1 (es) 2009-11-20 2012-08-22 Gp Pharm, S.A. Cápsulas de principios activos farmacéuticos y ésteres de ácidos grasos poliinsaturados.
CN101766573B (zh) 2010-02-05 2013-02-13 上海安必生制药技术有限公司 硫酸氢氯吡格雷固体制剂的制备工艺
CN101851247B (zh) * 2010-06-04 2013-05-29 浙江华海药业股份有限公司 含有硫酸氢氯吡格雷晶体颗粒的组合物

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2363053C (fr) * 2001-11-09 2011-01-25 Bernard Charles Sherman Formulation pour pastilles de bisulfate de clopidogrel
EP1606231A1 (fr) * 2003-02-03 2005-12-21 Nadkarni, Sunil Sadanand Procede de preparation de clopidogrel, ses sels et compositions pharmaceutiques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005048992A1 *

Also Published As

Publication number Publication date
CA2540965A1 (fr) 2005-06-02
AU2004290511A1 (en) 2005-06-02
WO2005048992A1 (fr) 2005-06-02
GB0325603D0 (en) 2003-12-10
BRPI0416109A (pt) 2007-01-02
JP2007527414A (ja) 2007-09-27
CN101848705A (zh) 2010-09-29

Similar Documents

Publication Publication Date Title
EP1682096A1 (fr) Procede permettant de preparer des compositions de clopidogrel
US10925896B2 (en) Pharmaceutical compositions
AU2002237462B2 (en) Oral pharmaceutical composition of cefpodoxime proxetil
WO2008057266A2 (fr) Liants et produits de granulation secs, et leur utilisation
WO2014097209A1 (fr) Composition pharmaceutique contenant du candésartan cilexetil et de l'amlodipine
US20040037880A1 (en) Extended release formulation of divalproex sodium
US20110060008A1 (en) Pharmaceutical composition containing acetylcholine esterase inhibitor and method for the preparation thereof
MXPA06004935A (en) Process for preparing clopidogrel compositions
JPH10502937A (ja) フシジン酸錠剤の製法
WO2015001569A1 (fr) Composition pharmaceutique solide d'ivabradine à administrer par voie orale
EP2403500A2 (fr) Comprimés d'olanzapine stables et leur procédé de préparation
JP2007246539A (ja) 速溶性医薬組成物

Legal Events

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

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20060606

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LU MC NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: HR YU

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RAX Requested extension states of the european patent have changed

Extension state: YU

Payment date: 20060606

Extension state: HR

Payment date: 20060606

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

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20070317