| 摘要 |
PROBLEM TO BE SOLVED: To provide an industrial method for producing crystal polymorphism type I (hereinafter, referred also to as "form I crystal") of clopidogrel sulfate.SOLUTION: There is provided a method for producing a form I crystal in a short time in high crystallization rate and reproducibility by converting free clopidogrel to a sulfate in a solution containing dissolved clopidogrel and, at the same time, adding a specific amount of powdery crystal seed of the form I crystal of clopidogrel sulfate having controlled particle size into the solution containing the converted clopidogrel sulfate. Specifically, the method for producing the form I crystal of clopidogrel sulfate is characterized by addition of concentrated sulfuric acid to 2-butanol solution containing free clopidogrel to convert the free clopidogrel to clopidogrel sulfate in the solution, and addition of a controlled amount of the powdery crystal seed of the form I crystal of clopidogrel sulfate having a controlled particle size to crystallize the sulfate. |
