Polymorphic transformations during pharmaceutical processing

Otsuka, M. Hasegawa, H. Matsuda, Y., Effect of polymorphic transformation during the extrusion-granulation process on the pharmaceutical properties of carbamazepine granules Chem. Pharm. Bull. 1997, 45, 894-898. 

Polymorphic transformation can take place during pharmaceutical processing, such as particle size reduction, wet granulation, drying, and even during the compaction process.f Tests employed to determine crystal... 

Zhang, G.G. Law, D. Schmitt, E.A. Qiu, Y. Bauer, M. Bauer, J. Spanton, S. Henry, R. Quick, J. Dziki, W. Porter, W. Morris, J. Highleyman, L. Phase transformation considerations during process development and manufacture of solid oral dosage forms [Crystallization and solid state properties of molecules of pharmaceutical interest] Ritonavir an extraordinary example of conformational polymorphism Ritonavir manufacturing problems. Adv. Drug. Deliv. Rev. 2004, 56 (3), 371-390. 

Polymorphism is ubiquitous in the pharmaceutical industry. The approval of a new drug substance by the USFDA requires that all data on polymorphs of the lead molecule be documented. In general, a given substance can have any number of polymorphs but, under given experimental conditions, only one polymorph will be stable and all other polymorphs will be metastable. Since the presence of a metastable polymorph during processing often leads to phase transformation to the more stable polymorph, it is desirable to choose the thermodynamic polymorph for drug development. 

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