Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberWO2005021511 A1
Publication typeApplication
Application numberPCT/IN2003/000288
Publication date10 Mar 2005
Filing date27 Aug 2003
Priority date27 Aug 2003
Publication numberPCT/2003/288, PCT/IN/2003/000288, PCT/IN/2003/00288, PCT/IN/3/000288, PCT/IN/3/00288, PCT/IN2003/000288, PCT/IN2003/00288, PCT/IN2003000288, PCT/IN200300288, PCT/IN3/000288, PCT/IN3/00288, PCT/IN3000288, PCT/IN300288, WO 2005/021511 A1, WO 2005021511 A1, WO 2005021511A1, WO-A1-2005021511, WO2005/021511A1, WO2005021511 A1, WO2005021511A1
InventorsReddy Bandi Parthasaradhi, Reddy Kura Rathnakar, Reddy Rapolu Raji, Reddy Dasari Muralidhara
ApplicantHetero Drugs Limited
Export CitationBiBTeX, EndNote, RefMan
External Links: Patentscope, Espacenet
A novel process for amorphous rosuvastatin calcium
WO 2005021511 A1
Abstract
The present invention provides a novel process for the preparation of amorphous rosuvastatin calcium.
Claims  (OCR text may contain errors)
We claim:
1. A process for preparation of amorphous rosuvastatin calcium, which comprises the steps of: a) dissolving rosuvastatin calcium in a solvent; and b) removing the solvent from the solution formed in step (a) by vacuum drying, freeze drying, lyophilization or spray drying; wherein the solvent is selcted from methanol, ethanol, isopropyl alcohol, tert- butyl alcohol, n-butyl alcohol, acetone, diethyl ketone, methylethyl ketone, methylisobutyl ketone, methylpropyl ketone, ethylacetate, methylacetate and a mixture thereof.
2. A process according to claim 1 , wherein the solvent is ethanol.
3. A process according to claim 1 , wherein the solvent is methanol.
4. A process according to claim 1, wherein the solvent is removed by vacuum drying.
5. A process according to claim 1, wherein the solvent is removed by spray drying.
6. A pharmaceutical composition comprising amorphous rosuvastatin calcium and a pharmaceutically acceptable carrier or diluent.
Description  (OCR text may contain errors)

A NOVEL PROCESS FOR AMORPHOUS ROSUVASTATIN CALCIUM

FILELD OF THE INVENTION

The present invention provides a novel process for the preparation of amorphous rosuvastatin calcium. BACKGROUND OF THE INVENTION

Rosuvastatin of formula (1 ):

or (+)-7-[4-(4-f!uorophenyl)-6-isopropyl-2-(N-methyl-N-methyl sulfonyl amino)pyrimidin-5-yl]-(3R,5S)-dihydroxy-(E)-6-heptenoic acid and its salts are 3- hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors and useful in the treatment of hypercholesterolemia, hyperlipoproteinemia and atherosclerosis. The therapeutic uses of rosuvastatin calcium and its related compounds were disclosed in US 5,260,440. Process for the preparation of amorphous(powder) rosuvastatin calcium was described in US 5,260,440. WO 00/42024 disclosed a crystalline form (form A) of rosuvastatin calcium. Various crystalline salts of rosuvastatin were disclosed in WO 01/60804. We have discovered a simple novel process for the preparation of sufficiently stable amorphous rosuvastatin calcium. The amorphous form produced by the novel process has better dissolution characteristics than the crystalline form known in the art. The object of the present invention is to provide a novel process for the preparation of amorphous rosuvastatin calcium and a pharmaceutical composition containing it.

DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention, there is provided a novel process for the preparation of amorphous rosuvastatin calcium. The amorphous rosuvastatin calcium is characterized by having broad x-ray diffraction spectrum as in figure 1. In accordance with the present invention, a process is provided for preparation of amorphous rosuvastatin calcium. Amorphous rosuvastatin calcium is prepared by dissolving rosuvastatin calcium in an alcohol, a ketone or an ester solvent and removing the solvent. The alcohol solvent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, tert-butyl alcohol and n-butyl alcohol. The ketone solvent is selected from the group consisting of acetone, diethyl ketone, methylethyl ketone, methylisobutyl ketone and methylpropyl ketone. The ester solvent is selected from ethylacetate and methylacetate. A mixture of two or more of these solvents may also be used. The preferable alcohols are ethanol and methanol. The solvent may be removed from the solution by vacuum drying, freeze- drying, lyophilization or spray drying. Rosuvastatin calcium obtained by a known process may be used in the process. In accordance with the present invention, there is provided a pharmaceutical composition comprising amorphous rosuvastatin calcium and a pharmaceutically acceptable carrier or diluent.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is ' a x-ray powder diffraction spectrum of amorphous rosuvastatin calcium. x-Ray powder diffraction spectrum was measured on a Bruker axs D8 advance x-ray powder diffractometer having a copper-Kr radiation.

The invention will now be further described by the following non-limiting examples. Example 1 Rosuvastatin calcium (25 gm) is dissolved in ethanol (250 ml). The solution is subjected to vacuum drying at about 55C for 10 hours to give 23 gm of amorphous rosuvastatin calcium. Example 2 Rosuvastatin calcium (25 gm) is dissolved in methanol (200 ml). The solution is subjected to spray drying at about 50C for 8 hours to give 22.5 gm of amorphous rosuvastatin calcium. Example 3 Rosuvastatin calcium (20 gm) is dissolved in water (200 ml). The solution is subjected to lyophilization to give 18 gm of amorphous rosuvastatin calcium.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
WO2001060804A1 *12 Feb 200123 Aug 2001Astrazeneca AbCrystalline salts of 7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3r,5s)-3,5-dihydroxyhept-6-enoic acid
WO2003097614A2 *21 May 200327 Nov 2003Ranbaxy Laboratories LimitedProcess for the preparation of rosuvastatin
US5260440 *12 Jun 19929 Nov 1993Shionogi Seiyaku Kabushiki KaishaPyrimidine derivatives
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
WO2005077917A1 *19 Jan 200525 Aug 2005Ranbaxy Laboratories LimitedAmorphous salts of rosuvastatin
US72448442 Dec 200417 Jul 2007Teva Pharmaceutical Industries Ltd.Reference standard for characterization of rosuvastatin
US739692724 Aug 20048 Jul 2008Teva Pharmaceutical Industries Ltd.Process for preparation of rosuvastatin calcium
US761220322 Feb 20063 Nov 2009Teva Pharmaceutical Industries Ltd.Rosuvastatin and salts thereof free of rosuvastatin alkylether and a process for the preparation thereof
US769200825 Jun 20076 Apr 2010Teva Pharmaceutical Industries Ltd.Reference standard for characterization of rosuvastatin
US769200925 Jun 20076 Apr 2010Teva Pharmaceutical Industries Ltd.Reference standard for characterization of rosuvastatin
US769201025 Jun 20076 Apr 2010Teva Pharmaceutical Industries Ltd.Reference standard for characterization of rosuvastatin
US774148225 Jun 200722 Jun 2010Teva Pharmaceutical Industries Ltd.Reference standard for characterization of rosuvastatin
US777703424 Nov 200417 Aug 2010Teva Pharmaceutical Industries Ltd.Crystalline ammonium salts of rosuvastatin
US786816916 Aug 200611 Jan 2011Teva Pharmaceutical Industries, Ltd.Crystalline rosuvastatin intermediate
US799417818 Sep 20079 Aug 2011Teva Pharmaceutical Industries, Ltd.Crystalline rosuvastatin calcium and compositions thereof for treatment of hyperlipidaemia
US806321111 Mar 200922 Nov 2011Teva Pharmaceutical Industries, Ltd.Rosuvastatin and salts thereof free of rosuvastatin alkylether and a process for the preparation thereof
US848709727 Jan 200916 Jul 2013Teva Pharmacedutical Industries Ltd.Reference standard for characterization of rosuvastatin
Classifications
International ClassificationA61K31/505, C07D239/42
Cooperative ClassificationC07D239/42, A61K31/505
European ClassificationA61K31/505, C07D239/42
Legal Events
DateCodeEventDescription
10 Mar 2005AKDesignated states
Kind code of ref document: A1
Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE 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 NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW
10 Mar 2005ALDesignated countries for regional patents
Kind code of ref document: A1
Designated state(s): GH GM KE LS MW MZ 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 IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
4 May 2005121Ep: the epo has been informed by wipo that ep was designated in this application
27 Sep 2006122Ep: pct app. not ent. europ. phase
26 Jul 2007NENPNon-entry into the national phase in:
Ref country code: JP