Recent Advances in Polymorph Discovery Methods of Organic Crystals

Polymorphism, the ability of the same substance to crystallize in more than one crystal structure, is a common phenomenon in organic crystals, influencing the physicochemical properties of solid materials in many important fields (foods, dyes and pigments, high energic materials, pharmaceuticals, etc.). The utilization of various polymorph discovery methods could increase the possibility of finding polymorphs with desired properties, achieving an optimal performance of the final product. Recently, there has been a steady development of polymorph discovery in both experimental and computational methods. To better guide the polymorph discovery, this paper reviews the recent advances in the polymorph screening methods of organic crystals, mainly including solution crystallization, melt crystallization, and crystal structure prediction. This paper also summarizes the nucleation theory in polymorphic systems to understand the formation of polymorphs and highlights the mechanisms of polymorph discovery by the kinds of methods. Finally, challenges of polymorph discovery are briefly discussed, aimed to shorten the screening time and make the polymorph discovery more effective.