PHARMACEUTICAL COMPOSITIONS COMPRISING CLOPIDOGREL BESYLATE AND METHODS FOR PREPARING THE SAME

摘要

A composition comprising clopidogrel besylate is provided to show high in vitro dissolution rate and have excellent stability without adding a separate additive such as an antioxidant by preparing the clopidogrel besylate in a solid dispersion with a copolymer of polyoxyethylene and polyoxypropylene and crospovidone as a disintegrant. A pharmaceutical composition comprises a clopidogrel besylate-containing solid dispersion prepared by dispersing 100 parts by weight of clopidogrel besylate, 3-15 parts by weight of a copolymer of polyoxyethylene and polyoxypropylene, 30-60 parts by weight of polyethyleneglycol and 5-20 parts by weight of crospovidone in 55-70 parts by weight of mannitol; and a pharmaceutically acceptable carrier such as a copolymer of polyoxyethylene and polyoxypropylene, crospovidone and a mixture thereof. A method for preparing the composition comprises the steps of: (a) dissolving clopidogrel besylate, a copolymer of polyoxyethylene and polyoxypropylene, polyethyleneglycol and crospovidone in 50-100% ethanol or an aqueous solution of ethanol; (b) dispersing the solution obtained from the step(a) in mannitol and then drying or spraying the solution of the step(a) with fluidizing the mannitol in a granulator to obtain a clopidogrel besylate-containing solid dispersion; and (c) mixing the clopidogrel besylate-containing solid dispersion with a pharmaceutically acceptable carrier. Further, the 0.2-0.4 wt.% of ethanol or an aqueous solution of ethanol is used based on the 100 wt.% of clopidogrel besylate.