WO2002057228A1 - Atorvastatine calcique - Google Patents

Atorvastatine calcique Download PDF

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Publication number
WO2002057228A1
WO2002057228A1 PCT/IN2001/000004 IN0100004W WO02057228A1 WO 2002057228 A1 WO2002057228 A1 WO 2002057228A1 IN 0100004 W IN0100004 W IN 0100004W WO 02057228 A1 WO02057228 A1 WO 02057228A1
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WO
WIPO (PCT)
Prior art keywords
atorvastatin calcium
amorphous
solvent
atorvastatin
calcium
Prior art date
Application number
PCT/IN2001/000004
Other languages
English (en)
Inventor
Mathew Joy
Sambasivam Ganesh
Original Assignee
Biocon India Limited
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 Biocon India Limited filed Critical Biocon India Limited
Priority to PCT/IN2001/000004 priority Critical patent/WO2002057228A1/fr
Publication of WO2002057228A1 publication Critical patent/WO2002057228A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics

Definitions

  • the present invention relates to a process for the production of amorphous atorvastatin calcium.
  • Atorvastatin calcium a synthetic HMG-CoA reductase inhibitor, is used for the treatment of hyperlipidemia and hypercholesterolemia, both of which are risk factors for arteriosclerosis and coronary heart disease.
  • PCT application discloses novel crystalline forms of atorvastatin calcium designated as Form 1. Form II, and Form IV and method for their preparation.
  • PCT application WO 97/03960 describes a procedure for converting the crystalline form of atorvastatin to the amorphous form.
  • PCT application WO 00/71 1 16 claims a process for the preparation of amorphous atorvastatin calcium where the crystalline form is dissolved in a non-hydroxilic solvent is treated with a non-polar hydrocarbon anti-solvent followed by the removal of the solvent to result in the amorphous form.
  • the present invention describes a process, which is ideal for large scale production of amorphous atorvastatin calcium.
  • the present invention provides a process for the preparation of atorvastatin calcium in an amorphous form which comprises dissolving the heterogeneous mixture of atorvastatin in a non- hydroxylic solvent followed by the addition of a suitable non- hydroxylic solvent to precipitate the product which is then isolated.
  • a suitable non- hydroxylic solvent to precipitate the product which is then isolated.
  • the solution of atorvastatin in a non- hydroxylic solvent is added to a non-hydroxylic solvent to induce precipitation.
  • the product can be isolated by any method known in the art such as by filtration, centrifugation or decantation. Typically, this product is isolated by filtration when any of the solvents within the scope of the process are used.
  • the present invention thus provides a simple and novel process for the preparation of amorphous atorvastatin calcium and hydrates thereof.
  • the starting material used in the instant invention comprises of a mixture of both amorphous and crystalline forms — henceforth referred to as heterogeneous mixture.
  • the present invention comprises of:
  • the non-hydroxylic solvent in step (i) is tetrahydrofuran.
  • the non-hydoxylic solvent used in step (ii) is diisopropyl ether.
  • the amorphous atorvastatin calcium is isolated by filtration.
  • Amorphous atorvastatin calcium prepared according to the process of the present invention may be characterized by its x- ray powder diffraction pattern ( Figures 2) as shown in the accompanied drawings.
  • X-ray powder diffraction patterns ( Figures 2) show no peaks which are characteristic of a heterogeneous mixmre of atorvastatin calcium ( Figure 1 of the accompanied drawings) thus demonstrating the amorphous nature of the product.
  • Figure 1 is the diffractogram of heterogeneous mixture of atorvastatin calcium.
  • the horizontal axis represents 2 ⁇ and the vertical axis corresponds to peak intensity.
  • Figure 2 is the diffractogram of amorphous atorvastatin calcium.
  • the horizontal axis represents 2 ⁇ and the vertical axis corresponds to peak intensity.

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

Abstract

L'invention concerne un procédé de préparation d'atorvastatine calcique amorphe et des hydrates de ce dernier, qui consiste a) à dissoudre un mélange hétérogène d'atorvastatine calcique dans un solvant non hydroxylique, b) à ajouter un solvant non hydroxylique ou à ajouter l'atorvastatine dissoute audit solvant pour précipiter l'atorvastatine calcique, et c) à retirer le solvant par filtration pour récupérer l'atorvastatine calcique amorphe.
PCT/IN2001/000004 2001-01-17 2001-01-17 Atorvastatine calcique WO2002057228A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/IN2001/000004 WO2002057228A1 (fr) 2001-01-17 2001-01-17 Atorvastatine calcique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2001/000004 WO2002057228A1 (fr) 2001-01-17 2001-01-17 Atorvastatine calcique

Publications (1)

Publication Number Publication Date
WO2002057228A1 true WO2002057228A1 (fr) 2002-07-25

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ID=11076296

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2001/000004 WO2002057228A1 (fr) 2001-01-17 2001-01-17 Atorvastatine calcique

Country Status (1)

Country Link
WO (1) WO2002057228A1 (fr)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004089895A1 (fr) * 2003-04-11 2004-10-21 Lek Pharmaceuticals D.D. Procede de preparation d'un sel d'atorvastatine calcique amorphe
US6867306B2 (en) 2001-01-19 2005-03-15 Biocon Limited Process for the synthesis of atorvastatin form v and phenylboronates as intermediate compounds
WO2005100313A1 (fr) * 2004-04-16 2005-10-27 Pfizer Products Inc. Procede pour former de l'atorvastatine calcique amorphe
US6992194B2 (en) 2000-11-30 2006-01-31 Teva Pharmaceutical Industries, Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
WO2006026531A1 (fr) * 2004-08-27 2006-03-09 Cordis Corporation Rapamycine amorphe exempte de solvant
US7144915B2 (en) 2001-06-29 2006-12-05 Warner-Lambert Company, Llc Crystalline forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1)
US7208608B2 (en) * 2002-02-01 2007-04-24 Zentiva A. S. Method of manufacturing an amorphous form of the hemi-calcium salt of (3R,5R) 7-3-phenyl-4-phenylcarbamoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yll-3, 5-dihydroxyheptanoic acid (actorvastatin)
WO2007057755A1 (fr) 2005-11-21 2007-05-24 Warner-Lambert Company Llc Nouvelles formes d’acide [r-(r*,r*)]-2-(4-fluorophenyl)-b,b-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoique magnesium
EP1810667A1 (fr) 2006-01-20 2007-07-25 KRKA, tovarna zdravil, d.d., Novo mesto Composition pharmaceutique contenant de l'atorvastatin amorphé
WO2008053312A2 (fr) * 2006-11-02 2008-05-08 Cadila Pharmaceuticals Limited Procédé de préparation d'un sel d'hémicalcium d'atorvastatine amorphe et intermédiaire de ce dernier
US7411075B1 (en) 2000-11-16 2008-08-12 Teva Pharmaceutical Industries Ltd. Polymorphic form of atorvastatin calcium
EP1977738A1 (fr) 2003-06-12 2008-10-08 Warner-Lambert Company LLC Compositions pharmaceutiques d'atorvastatine, qui sont produites sans procédé de granulation
US7501450B2 (en) * 2000-11-30 2009-03-10 Teva Pharaceutical Industries Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US7538136B2 (en) 2000-12-27 2009-05-26 Teva Pharmaceutical Industries Ltd. Crystalline forms of atorvastatin
US7655692B2 (en) 2003-06-12 2010-02-02 Pfizer Inc. Process for forming amorphous atorvastatin
US7790197B2 (en) 2003-06-09 2010-09-07 Warner-Lambert Company Llc Pharmaceutical compositions of atorvastatin
US7939675B2 (en) 2004-10-28 2011-05-10 Pfizer, Inc. Process for forming amorphous atorvastatin
WO2011088806A2 (fr) 2010-01-19 2011-07-28 Zentiva, K.S. Procédé de production industrielle d'une forme amorphe d'atorvastatine ayant une grande surface spécifique et utilisation de cette dernière dans une forme pharmaceutique.
US7994343B2 (en) 2004-03-17 2011-08-09 Ranbaxy Laboratories Limited Process for the production of atorvastatin calcium in amorphous form
US8026376B2 (en) 2004-07-20 2011-09-27 Pfizer, Inc. Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoicacid calcium salt (2:1)
EP2540704A2 (fr) 2004-05-05 2013-01-02 Pfizer Products Inc. Formes de sel de bénéthamine avec d'atorvastatine
US9034913B2 (en) 2005-09-21 2015-05-19 Pfizer Inc. Process for annealing amorphous atorvastatin
CN106432033A (zh) * 2016-10-21 2017-02-22 江苏阿尔法药业有限公司 一种无定形阿托伐他汀钙的制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5385929A (en) * 1994-05-04 1995-01-31 Warner-Lambert Company [(Hydroxyphenylamino) carbonyl] pyrroles
WO1997003960A1 (fr) * 1995-07-17 1997-02-06 Warner-Lambert Company NOUVEAU PROCEDE POUR LA PRODUCTION DE SEL DE CALCIUM D'ACIDE AMORPHE [R-(R*,R*))-2-(4-FLUOROPHENYL)-β,δ-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-(PHENYLAMINO)CARBONYLE]-1H-PYRROL-1-HEPTANOIQUE (2:1)
WO2000071116A1 (fr) * 1999-05-25 2000-11-30 Ranbaxy Laboratories Limited Procede relatif a la production de calcium d'atorvastatine amorphe
WO2001042209A1 (fr) * 1999-12-10 2001-06-14 Lek Pharmaceutical And Chemical Company D.D. Procede de preparation d'atorvastatine amorphe

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5385929A (en) * 1994-05-04 1995-01-31 Warner-Lambert Company [(Hydroxyphenylamino) carbonyl] pyrroles
WO1997003960A1 (fr) * 1995-07-17 1997-02-06 Warner-Lambert Company NOUVEAU PROCEDE POUR LA PRODUCTION DE SEL DE CALCIUM D'ACIDE AMORPHE [R-(R*,R*))-2-(4-FLUOROPHENYL)-β,δ-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-(PHENYLAMINO)CARBONYLE]-1H-PYRROL-1-HEPTANOIQUE (2:1)
WO2000071116A1 (fr) * 1999-05-25 2000-11-30 Ranbaxy Laboratories Limited Procede relatif a la production de calcium d'atorvastatine amorphe
WO2001042209A1 (fr) * 1999-12-10 2001-06-14 Lek Pharmaceutical And Chemical Company D.D. Procede de preparation d'atorvastatine amorphe

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BAUMANN K L ET AL: "THE CONVERGENT SYNTHESIS OF CI-981, AN OPTICALLY ACTIVE, HIGHLY POTENT, TISSUE SELECTIVE INHIBITOR OF HMG-COA REDUCTASE", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 33, no. 17, 21 April 1992 (1992-04-21), pages 2283 - 2284, XP000608147, ISSN: 0040-4039 *

Cited By (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7732623B2 (en) 1999-11-17 2010-06-08 Teva Pharmaceutical Industries Ltd. Polymorphic form of atorvastatin calcium
US7411075B1 (en) 2000-11-16 2008-08-12 Teva Pharmaceutical Industries Ltd. Polymorphic form of atorvastatin calcium
US7488750B2 (en) 2000-11-30 2009-02-10 Teva Pharmaceutical Industries Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US7342120B2 (en) 2000-11-30 2008-03-11 Teva Pharmaceutical Industries, Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US7144916B2 (en) 2000-11-30 2006-12-05 Teva Pharmaceutical Industries Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US7456297B2 (en) 2000-11-30 2008-11-25 Teva Pharmaceutical Industries Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US7151183B2 (en) 2000-11-30 2006-12-19 Teva Pharmaceutical Industries Ltd. Processes for preparing amorphous atorvastatin hemi-calcium
US7161012B2 (en) 2000-11-30 2007-01-09 Teva Pharmaceutical Industries Ltd. Processes for preparing amorphous atorvastatin hemi-calcium
US7189861B2 (en) 2000-11-30 2007-03-13 Teva Pharmaceutical Industries, Ltd. Processes for preparing amorphous atorvastatin hemi-calcium
US7468444B2 (en) 2000-11-30 2008-12-23 Teva Pharmaceutical Industries Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US7501450B2 (en) * 2000-11-30 2009-03-10 Teva Pharaceutical Industries Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US6992194B2 (en) 2000-11-30 2006-01-31 Teva Pharmaceutical Industries, Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US7256212B2 (en) 2000-11-30 2007-08-14 Teva Pharmaceutical Industries Ltd. Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
US7538136B2 (en) 2000-12-27 2009-05-26 Teva Pharmaceutical Industries Ltd. Crystalline forms of atorvastatin
US6867306B2 (en) 2001-01-19 2005-03-15 Biocon Limited Process for the synthesis of atorvastatin form v and phenylboronates as intermediate compounds
US7144915B2 (en) 2001-06-29 2006-12-05 Warner-Lambert Company, Llc Crystalline forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1)
US7208608B2 (en) * 2002-02-01 2007-04-24 Zentiva A. S. Method of manufacturing an amorphous form of the hemi-calcium salt of (3R,5R) 7-3-phenyl-4-phenylcarbamoyl-2-(4-fluorophenyl)-5-isopropyl-pyrrol-1-yll-3, 5-dihydroxyheptanoic acid (actorvastatin)
EA013500B1 (ru) * 2003-04-11 2010-06-30 Лек Фармасьютиклз Д.Д. Способ получения аморфной кальциевой соли аторвастатина
US8697741B2 (en) 2003-04-11 2014-04-15 Lek Pharmaceutical D.D. Process for the preparation of amorphous calcium salt of atorvastatin
US8367848B2 (en) 2003-04-11 2013-02-05 Lek Pharmaceuticals D.D. Process for the preparation of amorphous calcium salt of atorvastatin
WO2004089895A1 (fr) * 2003-04-11 2004-10-21 Lek Pharmaceuticals D.D. Procede de preparation d'un sel d'atorvastatine calcique amorphe
US7790197B2 (en) 2003-06-09 2010-09-07 Warner-Lambert Company Llc Pharmaceutical compositions of atorvastatin
EP1977738A1 (fr) 2003-06-12 2008-10-08 Warner-Lambert Company LLC Compositions pharmaceutiques d'atorvastatine, qui sont produites sans procédé de granulation
US7655692B2 (en) 2003-06-12 2010-02-02 Pfizer Inc. Process for forming amorphous atorvastatin
US7994343B2 (en) 2004-03-17 2011-08-09 Ranbaxy Laboratories Limited Process for the production of atorvastatin calcium in amorphous form
WO2005100313A1 (fr) * 2004-04-16 2005-10-27 Pfizer Products Inc. Procede pour former de l'atorvastatine calcique amorphe
EP3581564A1 (fr) 2004-05-05 2019-12-18 Pfizer Products Inc. Formes de sel de diéthylamine d'acide heptanoïque [r-(r*,r*)]-2-(4-fluorophényl)-béta, delta-dihydroxy-5-(1-méthyléthyle)-3-phényl-4-[(phénylamino)carbonyl]-1h-pyrrole-1
EP2540704A2 (fr) 2004-05-05 2013-01-02 Pfizer Products Inc. Formes de sel de bénéthamine avec d'atorvastatine
US8895758B2 (en) 2004-07-20 2014-11-25 Warner-Lambert Company Llc Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β, δ-Dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1)
US8563750B2 (en) 2004-07-20 2013-10-22 Warner-Lambert Company Llc Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylmino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1)
US8026376B2 (en) 2004-07-20 2011-09-27 Pfizer, Inc. Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoicacid calcium salt (2:1)
US9790177B2 (en) 2004-07-20 2017-10-17 Warner-Lambert Company Llc Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-beta, gamma-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1)
US9481647B2 (en) 2004-07-20 2016-11-01 Warner-Lambert Company Llc Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β, δ-dihydroxy-5-(1-methylethyl)-3-Phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1)
US9199932B2 (en) 2004-07-20 2015-12-01 Warner-Lambert Company Llc Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1)
US7393952B2 (en) 2004-08-27 2008-07-01 Cordis Corporation Solvent free amorphous rapamycin
WO2006026531A1 (fr) * 2004-08-27 2006-03-09 Cordis Corporation Rapamycine amorphe exempte de solvant
US9056831B2 (en) 2004-10-28 2015-06-16 Pfizer Inc. Process for forming amorphous atorvastatin
US8686163B2 (en) 2004-10-28 2014-04-01 Pfizer Inc. Process for forming amorphous atorvastatin
US8258315B2 (en) 2004-10-28 2012-09-04 Pfizer Inc. Process for forming amorphous atorvastatin
US7939675B2 (en) 2004-10-28 2011-05-10 Pfizer, Inc. Process for forming amorphous atorvastatin
US9034913B2 (en) 2005-09-21 2015-05-19 Pfizer Inc. Process for annealing amorphous atorvastatin
US9428455B2 (en) 2005-09-21 2016-08-30 Pfizer Inc. Process for annealing amorphous atorvastatin
US9932307B2 (en) 2005-09-21 2018-04-03 Pfizer Inc. Process for annealing amorphous atorvastatin
US8383667B2 (en) 2005-11-21 2013-02-26 Warner Lambert Llc Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid magnesium
US8648109B2 (en) 2005-11-21 2014-02-11 Warner-Lambert Company Llc Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid magnesium
WO2007057755A1 (fr) 2005-11-21 2007-05-24 Warner-Lambert Company Llc Nouvelles formes d’acide [r-(r*,r*)]-2-(4-fluorophenyl)-b,b-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoique magnesium
US8084488B2 (en) 2005-11-21 2011-12-27 Pfizer Inc. Forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid magnesium
EP1810667A1 (fr) 2006-01-20 2007-07-25 KRKA, tovarna zdravil, d.d., Novo mesto Composition pharmaceutique contenant de l'atorvastatin amorphé
WO2008053312A2 (fr) * 2006-11-02 2008-05-08 Cadila Pharmaceuticals Limited Procédé de préparation d'un sel d'hémicalcium d'atorvastatine amorphe et intermédiaire de ce dernier
WO2008053312A3 (fr) * 2006-11-02 2009-04-23 Cadila Pharmaceuticals Ltd Procédé de préparation d'un sel d'hémicalcium d'atorvastatine amorphe et intermédiaire de ce dernier
WO2011088806A2 (fr) 2010-01-19 2011-07-28 Zentiva, K.S. Procédé de production industrielle d'une forme amorphe d'atorvastatine ayant une grande surface spécifique et utilisation de cette dernière dans une forme pharmaceutique.
CN106432033A (zh) * 2016-10-21 2017-02-22 江苏阿尔法药业有限公司 一种无定形阿托伐他汀钙的制备方法

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