Solid state concerns during drug discovery and development: thermodynamic and kinetic aspects of crystal polymorphism and the special cases of concomitant polymorphs, co-crystals and glasses

Abstract

During drug discovery and development the thermodynamics and kinetics of crystal form transitions must be studied and the fundamental properties of polymorphs must be identified. However, despite the accumulation of knowledge and experimental evidence that support the understanding of crystallization, its predictability still presents significant challenges. With the continuous development of new drug delivery technologies, even more complex situations arise such as difficult cases of polymorph selection, co-crystallization of different molecules, and manipulation of the crystallization environment for example amorphous solids. This review covers some fundamental thermodynamics and kinetics of simple system, before the discussions consider at these special cases and how the manipulation of thermodynamic and kinetic processes has increased our knowledge, understanding and application of crystallization science during the drug development process