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Effect of Supersaturation on Polymorphs of Clopidogrel Hydrogen Sulfate in Drowning‐out Crystallization
Author(s) -
Jim M.,
Kim K.J.
Publication year - 2012
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.201100717
Subject(s) - supersaturation , nucleation , crystallization , chemistry , chemical engineering , homogeneous , solvent , materials science , crystallography , inorganic chemistry , thermodynamics , organic chemistry , physics , engineering
To crystallize selectively forms I and II of clopidogrel hydrogen sulfate (CHS), nucleation behavior and supersaturation level were studied in mixed solvents such as formic acid/isopropanol, N , N ‐dimethylformamide/isopropanol, and N ‐methylpyrrolidone/isopropanol. The effect of supersaturation on induction time and nucleation rate was evaluated by comparison between nucleation mechanisms of seeded and unseeded crystallizations. Experimental results indicate that the polymorph obtained by crystallization depends on the type of seed crystals, amount of seed crystals, and seeding point. Homogeneous nucleation was desirable for the formation of form I. Form II corresponds to primary nucleation, i.e., homogeneous and heterogeneous nucleations.