Title of Invention	PROCESS FOR PREPARATION OF SUMATRIPTAN SUCCINATE CRYSTALLINE POLYMORPHS
Abstract	The present invention relates to a process for preparation of sumatriptan succinate crystalline form II. Thus, for example, sumatriptan free base is dissolved in methylene dichloride at reflux, succinic acid is added to the solution under stirring, stirring is continued at reflux and then isolating sumatriptan succinate crystalline form II from the solution at 2Soc.

Full Text

The present invention relates to a process for preparation of crystalline form of sumatriptan succinate. BACKGROUND OF THE INVENTION Sumatriptan succinate is a selective 5-Hydroxy tryptaminei receptor subtype agonist. Sumatriptan succinate is chemically designated as 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate (1:1). Sumatriptan succinate is currently used in the treatment of migraine. Sumatriptan is represented by the following structure: Sumatriptan and related compounds, processes for their preparation and their therapeutic uses were disclosed in US 4,816,470. Processes described in the literature do not produce well-defined, consistently reproducible crystalline forms of sumatriptan succinate. So, there is a need for stable, consistently reproducible crystalline forms of sumatriptan succinate for handling and for better pharmaceutical compositions. It has now been discovered that sumatriptan succinate can be prepared in two well-defined, stable and consistently reproducible crystalline forms. The object of the present invention is to provide a process for preparation of stable crystalline form of sumatriptan succinate. DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention, there is provided a novel crystalline form of sumatriptan succinate. This crystalline form is designated as sumatriptan succinate form II and typical form II x-ray powder diffraction spectrum of sumatriptan succinate form II is shown in figure 2. Sumatriptan succinate form II is characterized by peaks in the powder x-ray diffraction spectrum having two-theta angle positions at about 6.2, 7.7, 13.9, 15.1, 17.5, 17.9, 19.1, 19.4, 20.3, 20.8, 21.5, 22.4, 23.2, 23.9, 26.4 and 31.8 degrees. In accordance with the present invention, a process is provided for preparation of sumatriptan succinate form II. Sumatriptsfn succinate form II is prepared by dissolving sumatriptan free base in a chlorinated solvent, adding succinic acid to the solution and then isolating sumatriptan succinate form II from the solution. Sumatriptan free base may be dissolved in'a sufficient volume of the chlorinated solvent at elevated temperature (up to reflux). The amount of succinic acid is not critical, but 0.5 - 2.0 moles per mole of sumatriptan free base is preferable. The chlorinated solvents are selected from methylene dichloride, chloroform, carbon tetrachloride and ethylene dichloride. A mixture of these solvents may also be used. Preferable solvents are chloroform and methylene dichloride. Sumatriptan obtained by a previously known method may be used in the above processes. In accordance with the present invention, there is provided a pharmaceutical composition comprising sumatriptan succinate form II and a pharmaceutically acceptable carrier or diluent. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a x-ray powder diffraction spectrum of sumatriptan succinate form I. Figure 2 is a x-ray powder diffraction spectrum of sumatriptan succinate form II. x-Ray powder diffraction spectrum was measured on a Bruker axs D8 advance x-ray powder diffractometer having a copper-Ka radiation. The invention will now be further described by the following examples, which are illustrative rather than limiting. Example 1 Sumatriptan free base (5.0 gm) is mixed with chloroform (50 ml), the contents are heated to reflux to form a clear solution and then succinic acid (2 gm) is added to the solution. The reaction mixture is stirred for 3 hours at reflux temperature, allowed to cool to 25°C and filtered to give 5.1 gm of sumatriptan succinate form II. Sumatriptan free base (10.0 gm) is mixed with methylene dichloride (150 ml), the contents are heated to reflux and then succinic acid (4.0 gm) is added to the clear solution formed. The contents are stirred for 4 hours at reflux temperature, cooled slowly to 25°C and filtered to give 10.5 gm of sumatriptan succinate form II. We claim: 1. A process for the preparation of sumatriptan succinate crystalline polymorph form II, characterized by an x-ray powder diffraction spectrum having peaks expressed as 26 at 6.2, 7.7, 13.9, 15.1, 17.5, 17.9, 19.1, 19.4, 20.3, 20.8, 21.5, 22.4, 23.2, 23.9, 26.4 and 31.8 degrees as shown in figure 2, comprising the steps of: a) dissolving sumatriptan free base in a chlorinated solvent selected from the group consisting of methylene dichloride, chloroform, carbon tetrachloride and ethylene dichloride; b) adding succinic acid to the solution obtained in step (a); and c) isolating sumatriptan succinate crystalline form II from the solution obtained in step (b); 2. The process as claimed in claim 1, wherein the chlorinated solvent is chloroform. 3. The process as claimed in claim 1, wherein the chlorinated solvent is methylene dichloride.

Documents:

701-chenp-2003-abstract.pdf

701-chenp-2003-claims duplicate.pdf

701-chenp-2003-claims original.pdf

701-chenp-2003-correspondnece-others.pdf

701-chenp-2003-correspondnece-po.pdf

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

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

701-chenp-2003-drawings.pdf

701-chenp-2003-form 1.pdf

701-chenp-2003-form 3.pdf

701-chenp-2003-others.pdf