PROCESS FOR THE PREPARATION OF LANSOPRAZOLE WITH DESIRED PARTICLE-SIZE (19-May-2008)

Abstract

The present disclosure relates to a process for the preparation of lansoprazole with desired particle-size in high yield and purity with appropriate particle-size distribution.

Chemically, lansoprazole is 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl] methyl] sulfinyl] benzimidazole of Formula I and is known from U.S. Patent No. 4,628,098.  

Formula I

Lansoprazole is one of the well known gastric proton pump inhibitors and has a broad range of  antiulcerative and antigastric properties.  Other benzimidazole derivatives having similar properties include omeprazole, pantoprazole and rabeprazole.

Lansoprazole and other 2-(2-pyridylmethyl)sulfinylbenzimidazole derivatives tend to lose stability and undergo decomposition  at high temperature and when contami

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Several processes have been reported for the preparation and purification of lansoprazole such as those described in WO 99/47514, WO 2001/68594, WO 2001/21617, ES 2063705, WO 2002/074766, WO 2004/011455, U.S. Patent Nos. 6,603,009; 7,105,681; 5,374,730; 7,060,837; 6,998,490; 7,022,859; and 7,064,213.

U.S. Patent 4,628,098 discloses the purification of crude lansoprazole involving column chromatography (silica gel, eluent; ethyl acetate) and further by crystallization from a mixture of solvents.  It provides tedious and time consuming purification process which is not viable for commercial production.

U.S. Patent No. 6,180,652 describes a method for the purification of lansoprazole through its acetone complex.  This permits the separation of sulfone derivative but brings the drawback of low yield of the desired sulfoxide.

U.S. Patent No. 6,002,011 describes a process for preparing lansoprazole, which involves subjecting water and alcohol solvate crystals of the compound to being suspended, left standing or stirred in water for a sufficient time, and drying the resultant product.  

WO 2003/062223 describes purification of sulfone and sulfide contami

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U.S. Patent No. 6,919,459 describes aprocess for purification of lansoprazole involving extraction with aqueous alkaline solution at high pH.

U.S. Patent No. 6,909,004 describes a method of purifying lansoprazole from a solution of crude lansoprazole in organic solvent or a mixture of organic solvent and water in presence of amine compounds.

Although attempts have been made and literature reports a number of methods for preparation and purification of lansoprazole there are no references related to preparation of lansoprazole with desired particle-size and specified particle-size distribution.  Moreover, the methods employed for obtaining pure cr...