PROCESS
FOR THE PREPARATION OF LANSOPRAZOLE WITH DESIRED PARTICLE-SIZE
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
nat
ed
with traces of a solvent, particularly
water, in their crystal structure.
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
nat
ed
lansoprazole by treating it with potassium carbo
nat
e
in aqueous alcohol at elevated temperature.
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...
