Title of Invention	A PROCESS FOR PREPARATION OF IRBESARTAN CRYSTALLINE POLYMORPH
Abstract	The present invention relates to a process for preparation of irbesartan crystalline form c. Thus, for example,irbesatan is stirred with tetrahydrofuran,heated to reflux, stirring is continued at reflux and then isolating irbesartan crystalline form C from the solution at 10oC.

Full Text

The present invention relates to a novel crystalline form of irbesartan, to process for its preparation and a pharmaceutical composition containing it. BACKGROUND OF THE INVENTION Irbesartan or 2-Butyl-3-[[2'-(1 H-tetrazol-5-yl)[1,1 '-biphenyl]-4-yi]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one, which has the formula (1): is a powerful angiotensin II receptor antagonist. US 5,629,331 describes two crystalline forms of irbesartan (form A, B). It has now been found that irbesartan can be prepared in a novel crystalline form (form C). The novel crystalline form is at least as stable as form A or form B and is not spontaneously converted to the previously known forms. The novel form is found to be suitable for pharmaceutical preparations. The object of the present invention is to provide a stable novel crystalline form of irbesartan, a process for preparing it and a pharmaceutical composition containing it. DETAILED DESCRIPTION OF THE INVENTION According to one aspect of the present invention, there is provided a novel crystalline form of irbesartan, designated as form C, characterized by an x-ray powder diffraction pattern having peaks expressed as 29 at about 8.3, 8.7, 10.1, 11.8, 15.0, 15.5, 16.4, 16.8, 17.5, 18.3, 19.1, 20.3, 21.1, 21.7, 23.6, 25.1, 25,5, 26.4, 26.8, 27.2, 28.1, 29.0 and 29.4 degrees. Figure 1 shows typical form C x-ray powder diffraction spectrum. According to another aspect of the present invention, there is provided a process for preparation of the form C of irbesartan. Thus, irbesartan is mixed with a suitable solvent and irbesartan form C is isolated from the mixture. Preferably, the mixture of irbesartan and a suitable solvent is heated to reflux and the contents are filtered at about 5°C to 25°C. The suitable solvent is tetrahydrofuran or 1,4-dioxane; or a mixture thereof. Suitable solvent mixed with any other solvent/s like water may be used as long as irbesartan form C can be isolated from the solvent mixture. Previously known form of irbesartan or irbesartan prepared by a known method may be used in the process. According to another aspect of the present invention there is provided a pharmaceutical composition comprising irbesartan form C. Irbesartan form C may be formulated in a form suitable for oral administration or injection. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a x-ray powder diffraction spectrum of irbesartan form C. x-Ray powder diffraction spectrum was measured on a Siemens D5000 x-ray powder diffractometer having a copper-Ka radiation. The following examples are given for the purpose of illustrating the present invention and should not be considered as limitations on the scope or spirit of the invention. Example 1 Irbesartan (5.0 gm, obtained by the process described in example 5 of US 5,270,317) is mixed with tetrahydrofuran (350 ml), heated to reflux and maintained under reflux temperature for 30 minutes. The contents are cooled to 10°C. The separated crystals are collected by filtration to give 4.2 gm irbesartan form C. Example 2 Example 1 is repeated using irbesartan form A for irbesartan to give irbesartan form C. Example 3 Example 1 is repeated using irbesartan form B for irbesartan to give irbesartan form C. Example 4 The mixture of Irbesartan (5.0 gm, obtained by process described in example 5 of US 5,270,317) and 1.4-dioxane (100 ml) is stirred for 5 hours at 20°C to 25°C. The solid is collected by filtration to give 4.7 gm irbesartan form C. Example 5 Irbesartan (5.0 gm, obtained by process described in example 5 of US 5,270,317) is added to a mixture of tetrahydrofuran (320 ml) and water (3 ml). The contents are heated to reflux, maintained under reflux temperature for 30 minutes and then cooled to 10°C. The separated crystals are collected by filtration to give 3.8 gm irbesartan form C. We claim: 1. A process for the preparation of the crystalline irbesartan form C, characterized by an x-ray powder diffraction pattern having peaks expressed as 29 at about 8.3, 8.7, 10.1, 11.8, 15.0, 15.5, 16.4, 16.8, 17.5, 18.3, 19.1. 20.3, 21.1, 21.7, 23.6, 25.1, 25.5, 26.4, 26.8, 27.2, 28.1, 29.0 and 29.4 degrees as shown in figure 1; as herein described comprising the steps of: a) mixing irbesartan with a suitable solvent selected from tetrahydrofuran and 1,4-dioxane; b) maintaining the mixture obtained in step (a) for 30 minutes to 5 hours at 20°C to reflux temperature of the solvent used; and c) isolating irbesartan crystalline form C at 5°C to 25°C from the reaction mass obtained in step (b). 2. The process according to claim 1, wherein the solvent used in step (a) is tetrahydrofuran. 3. The process according to claim 1, wherein the solvent used in step (a) is 1,4- dioxane.

Documents:

825-chenp-2003-abstract.pdf

825-chenp-2003-claims duplicate.pdf

825-chenp-2003-claims original.pdf

825-chenp-2003-correspondnece-others.pdf

825-chenp-2003-correspondnece-po.pdf

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

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

825-chenp-2003-drawings.pdf

825-chenp-2003-form 1.pdf

825-chenp-2003-form 3.pdf

825-chenp-2003-form 4.pdf

825-chenp-2003-form 5.pdf