Mechanochemical Transformations of Pharmaceutical Cocrystals: Polymorphs and Coformer Exchange.

Transformations of solid samples under solvent-free or minimal solvent conditions set the future trend and define a modern strategy for the production of new materials. Of the various technologies tested in recent years, the mechanochemical approach seems to be the most promising for economic and ecological reasons. The aim of this review article is to present the current state of art in solid state research on binary systems, which have found numerous applications in the pharmaceutical and materials science industries. This article is divided into three sections. In the first part, we describe the new equipment improvements, which include the innovative application of thermo-mechanochemistry, sono-mechanochemistry, photo-mechanochemistry, electro-mechanochemistry, as well as resonant acoustic mixing (RAM), and transformation under high-speed sample spinning ("SpeedMixing"). A brief description of techniques dedicated to ex-situ and in-situ studies of progress and the mechanism of solid matter transformation (PXRD, FTIR, Raman and NMR spectroscopy) is presented. In the second section, we discuss the problem of cocrystal polymorphism highlighting the issue related with correlation between mechanochemical parameters (time, temperature, energy, molar ratio, solvent used as a liquid assistant, surface energy, crystal size, crystal shape) and preference for the formation of requested polymorph. The last part is devoted to the description of the processes of coformer exchange in binary systems forced by mechanical and/or thermal stimuli. The influence of the thermodynamic factor on the selection of the best-suited partner for the formation of a two-component stable structure is presented.