Title of Invention	A NOVEL PROCESS FOR AMORPHOUS ROSUVASTATIN CALCIUM
Abstract	The present invention provides a novel process for the preparation of amorphous rosuvastatin calcium.

Full Text

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-fluorophenyl)-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 v^ith 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 anu 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 ACCOMPANYING DRAWINGS Figure 1 is a x-ray powder diffraction spectrum of amorphous rn x-Ray powder diffraction spectrum was measured on a Bruker axs D8 advance x-ray powder diffractometer having a copper-Kr radiation. Tiie 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 55°C 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 50°C 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 :c subjected to lyophilization to give 18 gm of amorphous rosuvastatin calcium. 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. The process according to claim 1, wherein the solvent is ethanol. 3. The process according to claim 1, wherein the solvent is methanol. 4. The process according to claim 1, wherein the solvent is removed by vacuum drying. 5. The process according to claim 1, wherein the solvent is removed by spray drying. 6. The process according to claim 1, wherein amorphous rosuvastatin calcium obtained is used in pharmaceutical composition.

Documents:

1347-chenp-2003-abstract.pdf

1347-chenp-2003-claims duplicate.pdf

1347-chenp-2003-claims original.pdf

1347-chenp-2003-correspondnece-others.pdf

1347-chenp-2003-correspondnece-po.pdf

1347-chenp-2003-description(complete) duplicate.pdf

1347-chenp-2003-description(complete) original.pdf

1347-chenp-2003-drawings.pdf

1347-chenp-2003-form 1.pdf

1347-chenp-2003-form 4.pdf

1347-chenp-2003-form 5.pdf