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
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 |
|---|---|---|---|
| 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 |
| EP05718213A EP1761489A1 (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 | ||
| IN562/DEL/2005 | 2005-03-16 | ||
| IN562DE2005 | 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 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 (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3581564A1 (en) * | 2004-05-05 | 2019-12-18 | Pfizer Products Inc. | Diethylamine salt forms of [r-(r*,r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid |
| WO2006011041A2 (en) | 2004-07-20 | 2006-02-02 | Warner-Lambert Company Llc | Crystalline forms of (r-(r*))-2-(4-fluorophenyl)-beta, gamma-dihydroxy-5-(1-methylethyl)-3-phenyl-4-((phenylamino)carbonyl)-1h-pyrrole-1-hept anoic acid calcium salt (2:1) |
| EP1793815A4 (en) * | 2004-09-30 | 2010-12-29 | Reddys Lab Ltd Dr | Amorphous atorvastatin calcium |
| AU2006281229A1 (en) | 2005-08-15 | 2007-02-22 | Arrow International Limited | Crystalline and amorphous sodium atorvastatin |
| GB0613567D0 (en) * | 2006-07-07 | 2006-08-16 | Arrow Int Ltd | Crystalline sodium atorvastatin |
| AU2006281237A1 (en) | 2005-08-15 | 2007-02-22 | Arrow International Limited | Crystalline and amorphous sodium atorvastatin |
| GB0613566D0 (en) * | 2006-07-07 | 2006-08-16 | Arrow Int Ltd | Crystalline sodium atorvastatin |
| US8080672B2 (en) | 2005-12-13 | 2011-12-20 | Teva Pharmaceutical Industries Ltd. | Crystal form of atorvastatin hemi-calcium and processes for preparation thereof |
| WO2008108572A1 (en) * | 2007-03-02 | 2008-09-12 | Dong-A Pharm. Co., Ltd. | Novel 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 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997003959A1 (en) * | 1995-07-17 | 1997-02-06 | Warner-Lambert Company | 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) |
| SI20425A (en) * | 1999-12-10 | 2001-06-30 | LEK tovarna farmacevtskih in kemi�nih izdelkov d.d. | Preparation of amorphous atorvastatin |
| SK6592003A3 (en) * | 2000-11-03 | 2004-01-08 | Teva Pharma | Atorvastatin hemi-calcium form VII |
| MXPA03005879A (en) * | 2000-12-27 | 2003-09-10 | Ciba Sc Holding Ag | Crystalline forms of atorvastatin. |
| GEP20053546B (en) * | 2001-06-29 | 2005-06-10 | Warner Lambert Co | 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) |
| IL159626A0 (en) * | 2001-07-30 | 2004-06-01 | Reddys Lab Ltd Dr | Crystalline forms of atorvastatin calcium and processes for the preparation thereof |
-
2005
- 2005-03-17 EP EP05718213A patent/EP1761489A1/en not_active Withdrawn
- 2005-03-17 AU AU2005223491A patent/AU2005223491A1/en not_active Abandoned
- 2005-03-17 CA CA002560282A patent/CA2560282A1/en not_active Abandoned
- 2005-03-17 WO PCT/IB2005/000687 patent/WO2005090301A1/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005090301A1 (en) | 2005-09-29 |
| CA2560282A1 (en) | 2005-09-29 |
| EP1761489A1 (en) | 2007-03-14 |
| AU2005223491A1 (en) | 2005-09-29 |
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