Crystal Engineering of Organic Cocrystals by the Solid-State Grinding Approach

Crystal engineering of organic cocrystals is gaining interest across a variety of disciplines. The solid-state grinding approach to preparing cocrystals is an alternative to the traditional method of solution crystallisation, and possesses several distinct advantages. This review first demonstrates that the approach of solid-state cocrystal preparation is well established in the literature by providing a brief historical account of its applications. Several cases are then examined in which certain cocrystal materials can be prepared only by solid-state grinding methodologies. These examples underscore the importance of this approach in the search for new cocrystal materials. This is particularly advantageous when searching for new cocrystal stoichiometries. The focus then turns to a recent modification of the solid-state grinding process, in which small quantities of solvent are introduced either to increase solid-state cocrystallisation kinetics or to provide polymorph control – the latter having particular significance in the pharmaceutical field. Finally, a significant analytical advancement with direct implications for the field of solid-state cocrystal preparation is considered by examining recent examples of crystal structure determination from powder X-ray diffraction data.