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Spherical Crystallization and the Mechanism of Clopidogrel Hydrogen Sulfate
Author(s) -
Chen Mingyang,
Du Shichao,
Zhang Teng,
Wang Qi,
Wu Songgu,
Gong Junbo
Publication year - 2018
Publication title -
chemical engineering and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.403
H-Index - 81
eISSN - 1521-4125
pISSN - 0930-7516
DOI - 10.1002/ceat.201700661
Subject(s) - nucleation , crystallization , economies of agglomeration , crystal (programming language) , chemical engineering , materials science , hydrogen , mechanism (biology) , crystal growth , crystallography , chemistry , organic chemistry , physics , engineering , computer science , quantum mechanics , programming language
Clopidogrel hydrogen sulfate is a famous antiplatelet agent for vascular disease. Forms I and II can be used as medicine. However, both forms exhibit low density and flowability. In addition, form I shows low polymorph stability. To solve these problems, spherical crystallization technologies were developed for the two forms. For form I, the mechanism was studied and turned out to be 2D nucleation and spherulitic crystal growth. In case of form II, the spherical crystallization process was based on agglomeration. The influence of temperature, acid, and crystal seed were investigated. The optimized spherical forms I and II showed much higher density and flowability as well as high polymorph stability.