Polymorphism of pharmaceuticals

Abstract

Chapter 7 deals with polymorphism in pharmaceuticals. Following a discussion of the problem of determining the statistics of the occurrence of polymorphism in pharmaceuticals, I present a discussion and examples of the connection between polymorphism and the rate of dissolution and solubility, bioavailability, and the importance of phase changes and mixtures of forms in pharmaceutical preparations. I survey some of the considerations and techniques involved in screening for crystal forms: solvent selection, specific screening for solvates and hydrates, gel crystallization, crystallization in ionic liquids, the challenge of difficult to obtain stable forms and unstable new forms, and the outlook on new techniques and conditions for crystallization. The chapter also deals with polymorphism in pharmaceutical co-crystals, excipients, and amorphous forms and the importance and utility of chemical microscopy in the study of polymorphism of pharmaceuticals.