WO2005090301B1 - Crystalline form of atorvastatin hemi calcium - Google Patents
Crystalline form of atorvastatin hemi calciumInfo
- Publication number
- WO2005090301B1 WO2005090301B1 PCT/IB2005/000687 IB2005000687W WO2005090301B1 WO 2005090301 B1 WO2005090301 B1 WO 2005090301B1 IB 2005000687 W IB2005000687 W IB 2005000687W WO 2005090301 B1 WO2005090301 B1 WO 2005090301B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- atorvastatin hemi
- hemi calcium
- crystalline form
- hydrates
- calcium
- 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.)
- Ceased
Links
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
Landscapes
- 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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Abstract
The present invention relates to novel crystalline form R of atorvastatin hemi calcium salt and hydrates thereof useful as pharmaceutical agents, to methods for their production and isolation, to pharmaceutical compositions which include novel crystalline form R of atorvastatin hemi calcium salt and hydrates thereof and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment.
Claims
20 AMENDED CLAIMS [received by the International Bureau on 04 October 2005 (04.10.2005); original claims 1-23 replaced by amended claims 1-14 (2 pages)]
We claim: 1. A crystalline form R of atorvastatin hemi calcium exhibiting an XRD spectrum comprising peaks at about 8.62, 10.16 and 19.32 degrees two-theta.
2. The crystalline form R of atorvastatin hemi calcium of claim 1, further comprising peaks at about 3.6, 8.24, 18.12, 18.36, 20.44, 20.82, 21.22 and 23.82 degrees two- theta.
3. A process for preparing crystalline form R of atorvastatin hemi calcium and hydrates thereof according to any of the claims above, comprising dissolving crude atorvastatin hemi calcium in a mixture of tetrahydrofuran and methanol, and precipitating with water to obtain a crystalline form R of atorvastatin hemi calcium.
4. The process according to claim 3, wherein crude atorvastatin hemi calcium contains unreacted compounds, side products or other impurities.
5. The process according to claim 3, wherein the mixture of crude atorvastatin hemi calcium and solvent system is heated to reflux.
6. The process according to claim 5, wherein the crystalline form R of atorvastatin hemi calcium and hydrates thereof is isolated by cooling the mixture to a temperature of about 20 to about 40°C.
7. The process according to claim 3 to 6, wherein tetrahydrofuran, methanol and water are used in a volume ratio of about 1:1:4.
8. A process for the preparation of a stabilized amorphous form of atorvastatin hemi calcium, comprising dissolving the crystalline form R of atorvastatin hemi calcium and hydrates thereof in a solvent, and adding the anti-solvent to the resulting solution, wherein an antioxidant is added to the atorvastatin hemi calcium solution to obtain stabilized amorphous atorvastatin hemi calcium.
9. The process according to claim 8, wherein an antioxidant is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene and tertiary-butylated hydroquinone.
10. A pharmaceutical composition comprising a crystalline form R of atorvastatin hemi calcium or hydrates thereof according to claims 1 or 2, along with pharmaceutically acceptable excipients, diluents and carriers.
11. A method for treatment or prevention of hyperlipidemia, hypercholesterolemia, Alzheimer's disease atherosclerosis, xanthoma and in synergism with other drugs for treatment of phytosterolemia lipase deficiency and the like, which comprises administering to a patient in need thereof, a therapeutically effective amount of crystalline form R of atorvastatin hemi calcium or hydrates thereof according to claims 1 or 2.
12. The use of the crystalline form R of atorvastatin hemi calcium and hydrates thereof according to claims 1 or 2 in the manufacture of a medicament for the treatment or prevention of hyperlipidemia, hypercholesterolemia, Alzheimer's disease, atherosclerosis, xanthoma and in synergism with other drugs for treatment of phytosterolemia lipase deficiency and the like.
13. A crystalline atorvastatin hemi calcium form R or a hydrate thereof having a powder XRD pattern substantially as depicted in FIG. 1.
14. A crystalline atorvastatin hemi calcium form R or a hydrate thereof having IR spectrum substantially as depicted in FIG. 2.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05718213A EP1761489A1 (en) | 2004-03-17 | 2005-03-17 | Crystalline form of atorvastatin hemi calcium |
| CA002560282A CA2560282A1 (en) | 2004-03-17 | 2005-03-17 | Crystalline form of atorvastatin hemi calcium |
| AU2005223491A AU2005223491A1 (en) | 2004-03-17 | 2005-03-17 | Crystalline form of atorvastatin hemi calcium |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN491/DEL/2004 | 2004-03-17 | ||
| IN491DE2004 | 2004-03-17 | ||
| IN562DE2005 | 2005-03-16 | ||
| IN562/DEL/2005 | 2005-03-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2005090301A1 WO2005090301A1 (en) | 2005-09-29 |
| WO2005090301B1 true WO2005090301B1 (en) | 2005-12-01 |
Family
ID=34993618
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2005/000687 Ceased WO2005090301A1 (en) | 2004-03-17 | 2005-03-17 | Crystalline form of atorvastatin hemi calcium |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1761489A1 (en) |
| AU (1) | AU2005223491A1 (en) |
| CA (1) | CA2560282A1 (en) |
| WO (1) | WO2005090301A1 (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007536373A (en) * | 2004-05-05 | 2007-12-13 | ファイザー・プロダクツ・インク | Salt form of atorvastatin |
| CA2573771C (en) | 2004-07-20 | 2011-05-10 | Warner-Lambert Company Llc | Novel forms of [r-(r*,r*)]-2-(4-fluorophenyl)-.beta., .gamma.-dihydroxy-5-(1-menthylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid calcium salt (2:1) |
| JP2008514722A (en) * | 2004-09-30 | 2008-05-08 | ドクター レディズ ラボラトリーズ リミテッド | Amorphous atorvastatin calcium |
| GB0613567D0 (en) * | 2006-07-07 | 2006-08-16 | Arrow Int Ltd | Crystalline sodium atorvastatin |
| CN101268047B (en) * | 2005-08-15 | 2012-11-07 | 箭锋国际有限公司 | Crystalline and amorphous sodium atorvastatin |
| BRPI0614279A2 (en) | 2005-08-15 | 2012-11-06 | Arrow Int Ltd | crystalline and amorphous sodium atorvastatin |
| GB0613566D0 (en) * | 2006-07-07 | 2006-08-16 | Arrow Int Ltd | Crystalline sodium atorvastatin |
| EP1966133A2 (en) | 2005-12-13 | 2008-09-10 | Teva Pharmaceutical Industries Ltd. | Crystal form of atorvastatin hemi-calcium and processes for preparation thereof |
| US7915302B2 (en) * | 2007-03-02 | 2011-03-29 | Dong-A Pharm. Co., Ltd. | Crystal forms of pyrrolylheptanoic acid derivatives |
| EP2075246A1 (en) | 2007-12-27 | 2009-07-01 | M. J. Institute of Research | A process for preparation of amorphous form of atorvastatin hemi-calcium salt |
| WO2009090544A2 (en) * | 2008-01-16 | 2009-07-23 | Matrix Laboratories Limited | Process for producing amorphous atorvastatin calcium |
| WO2025147589A1 (en) | 2024-01-05 | 2025-07-10 | Osanni Bio, Inc. | Implants, compositions, and methods for treating retinal diseases and disorders |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3296564B2 (en) * | 1995-07-17 | 2002-07-02 | ワーナー−ランバート・コンパニー | Crystalline [R- (R ▲ *, R ▲ *)]-2- (4-fluorophenyl) -β, δ-dihydroxy-5- (1-methylethyl) -3-phenyl-4 -[(Phenylamino) carbonyl] -1H-pyrrole-1-heptanoic acid hemicalcium salt (atorvastatin) |
| SI20425A (en) * | 1999-12-10 | 2001-06-30 | LEK tovarna farmacevtskih in kemi�nih izdelkov d.d. | Preparation of amorphous atorvastatin |
| CN1535139A (en) * | 2000-11-03 | 2004-10-06 | ������ҩ��ҵ����˾ | Atorvastatin hemi-calcium form VII |
| EP1345896B1 (en) * | 2000-12-27 | 2009-01-07 | Teva Pharmaceutical Industries Limited | Crystalline forms of atorvastatin |
| CA2450111C (en) * | 2001-06-29 | 2006-02-07 | Warner-Lambert Company Llc | Crystalline forms of [r-(r*,r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid calcium salt(2:1)(atorvastatin) |
| CZ2004126A3 (en) * | 2001-07-30 | 2004-12-15 | Dr. Reddy's Laboratories Limited | Crystalline forms VI and VII of atorvastatin calcium salt |
-
2005
- 2005-03-17 WO PCT/IB2005/000687 patent/WO2005090301A1/en not_active Ceased
- 2005-03-17 CA CA002560282A patent/CA2560282A1/en not_active Abandoned
- 2005-03-17 AU AU2005223491A patent/AU2005223491A1/en not_active Abandoned
- 2005-03-17 EP EP05718213A patent/EP1761489A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005090301A1 (en) | 2005-09-29 |
| AU2005223491A1 (en) | 2005-09-29 |
| CA2560282A1 (en) | 2005-09-29 |
| EP1761489A1 (en) | 2007-03-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2220018C (en) | Crystalline [r-(r*,r*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid hemi calcium salt (atorvastatin) | |
| KR0167101B1 (en) | [R- (R *, R *)]-2- (4-fluorophenyl) -beta, delta-dihydroxy-5- (1-methylethyl) -3-phenyl-4-[(phenylamino) Carbonyl] -1H-pyrrole-1-heptanoic acid, lactone forms and salts thereof | |
| AU2002255479B2 (en) | Crystalline forms VI and VII of atorvastatin clacium | |
| SK5998A3 (en) | Form iii crystalline £r-(r*,r*)|-2-(4-fluorophenyl)-beta, delta dihydroxy-5-(1-methyl-ethyl)-3-phenyl-4-£(phenylamino)carbonyl)- -1h-pyrrole-1-heptanoic acid hemi calcium salt (atorvastatin) | |
| KR20030077003A (en) | Preparation of non-crystalline atorvastatin calcium | |
| WO2005090301B1 (en) | Crystalline form of atorvastatin hemi calcium | |
| AU2002255479A1 (en) | Crystalline forms VI and VII of atorvastatin clacium | |
| CA2526991A1 (en) | Piperidinium and pyrrolidinium derivatives as ligands for the muscarinic m3 receptor | |
| MXPA04006887A (en) | Solid salts benzazepine compounds and their use in the preparation of pharmaceuticals compounds. | |
| KR101012917B1 (en) | Novel Crystalline Form of Pyrrole Heptanoic Acid Compound | |
| EP2172452A1 (en) | Preparation of crystalline atorvastatin magnesium | |
| WO2007063551A1 (en) | POLYMORPHS OF [R-(R*, R*)]-2-(4-FLUOROPHENYL)-β,δ-DIHYDROXY-5-(l-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-lH-PYRROLE-l-HEPTANOIC ACID MAGNESIUM SALT (2: 1) | |
| WO2007132472A1 (en) | A crystalline form b4 of atorvastatin magnesium and a process thereof | |
| EP1732886A1 (en) | Polymorphs of atorvastatin tert.-butylester and use as intermediates for the preparation of atorvastatin | |
| US20070276027A1 (en) | Crystalline Forms of [R-(R* ,R*)]-2-(4-Fluorophenyl)-Beta, -Dihydroxy-5-(1-Methylethyl)-3-Phenyl-4-[(Phenylamino)Carbonyl]-1H-Pyrrole-1-Heptanoic Acid | |
| WO2006048894A1 (en) | Novel crystalline forms of atorvastatin calcium and processes for preparing them. | |
| GB2424880A (en) | Crystalline forms of atorvastatin sodium, processes for their preparation and their use in inhibiting HMG-CoA reductase | |
| EP0848704B2 (en) | Form iii crystalline ¬r-(r*,r*) -2-(4-fluorophenyl)-beta-delta-dihydroxy-5-(1-methyl-ethyl)-3-phenyl-4-¬(phenylamino)carbonyl -1h-pyrrole-1-heptanoic acid hemi calcium salt (atorvastatin) | |
| JPH04117382A (en) | 1-Methylcarbapenem derivatives and their production method | |
| EP1773769A1 (en) | Salt forms of atorvastatin | |
| KR20110050683A (en) | Polymorphic Forms of Granisetron Hydrochloride and Methods for Making the Same | |
| WO2021097159A1 (en) | Method for preparing heteroleptic triarylbismuthanes and compounds produced by the same | |
| US20100152274A1 (en) | Crystalline forms of atorvastatin 4-(nitrooxy) butyl ester |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| B | Later publication of amended claims |
Effective date: 20051004 |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2560282 Country of ref document: CA |
|
| NENP | Non-entry into the national phase in: |
Ref country code: DE |
|
| WWW | Wipo information: withdrawn in national office |
Country of ref document: DE |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2005223491 Country of ref document: AU |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 200580012704.X Country of ref document: CN |
|
| ENP | Entry into the national phase in: |
Ref document number: 2005223491 Country of ref document: AU Date of ref document: 20050317 Kind code of ref document: A |
|
| WWP | Wipo information: published in national office |
Ref document number: 2005223491 Country of ref document: AU |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2005718213 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 2005718213 Country of ref document: EP |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 2005718213 Country of ref document: EP |