Polymorph selection: the role of nucleation, crystal growth and molecular modeling.

Curr Opin Drug Discov Devel

Department of Chemical & Biological Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA.

Published: November 2007

Solution crystallization is an important separation and purification process used in the chemical, pharmaceutical and food industries. The quality of a crystalline product is generally judged by four main criteria: purity, crystal habit, particle size and solid form. Consistent production of the desired polymorph is crucial as the unanticipated emergence of a different crystal form may have severe consequences. Thus, the selection of a solid-state form for a crystalline product is vital and is ultimately based on knowledge of the properties of the other polymorphs. This review discusses the role of nucleation, crystal growth and molecular modeling on polymorphism in molecular crystals. Examples are presented demonstrating how the first two factors can govern the appearance of a particular crystalline form, and how the latter factor can be used as a tool for understanding polymorphism.

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