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IP.com Disclosure Number: IPCOM000200440D
Publication Date: 2010-Oct-13

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The present invention relates to amorphous mosapride citrate and processes for its preparation.

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The present invention relates to amorphous mosapride citrate and processes for its preparation.

Mosapride citrate dihydrate of Formula I chemically, (±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl] benzamide citrate dihydrate, marketed under the brand name Gasmotin® is indicated for gastrointestinal symptoms associated with chronic gastritis (heartburn, nausea/vomiting)


European Patent No. EP 0 243 959 B1 provides a process for the preparation of mosapride citrate dihydrate which involves dissolving mosapride free base in hot 10% aqueous citric acid solution and allowing the resulting solution to cool.  The precipitate is collected to give mosapride citrate dihydrate.  However, it does not suggest or teach any polymorphs of mosapride citrate.  When we prepared mosapride citrate using 10 % aqueous citric acid solution, we obtained mosapride citrate dihydrate in crystalline form.  This crystalline form is referred to herein as Form I.

WO 2003/106440, Korean Patent KR 750593 B1, Chinese Patent CN 1226295 C, Heterocycles, 38 (5), pp. 1033-1040; J. Med. Chem., 34 (2), pp. 616-624 (1991); Chem. Pharm. Bull. 42 (4), pp. 877-882 (1994), provides various processes for the preparation of mosapride and its intermediates.

Polymorphism is defined as the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecule in the crystal lattice.  Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, and the like.  Although these differences disappear once the compound is dissolved, they can appreciably influence the pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability.  Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph.  Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD) powder as well as single crystal, DSC, IR, Solid state NMR, Raman spectroscopy.

Solvent medium and mode of isolation play very important roles in obtaining a polymorphic form over another.

It has been disclosed in the art that the amorphous forms of a number of pharmaceutical compounds exhibit superior dissolution characteristics compared to crystalline forms [Konno T., Chem. Pharm. Bull., 38, 2003 (1990)].

The discovery of new solid state forms of a pharmaceutical compound provides a new opportunity to improve the performance characteristics of a pharmaceutical product.

The present inventors have now surprisingly and unexpectedly discovered a novel amorphous form of mosapride citrate.  The novel amorphous form of mosapride citrate of the present invention is suitable for preparing pharmaceutical compositions comprising amorphous form of mosapr...