Screening for new pharmaceutical solid forms using mechanochemistry: A practical guide

Abstract

Within the pharmaceutical industry, and elsewhere, the screening for new solid forms is a mandatory exercise for both existing and new chemical entities. This contribution focuses on mechanochemistry as a versatile approach for discovering new and alternative solid forms. Whilst a series of recently published extensive reviews exist which focus on mechanistic aspects and potential areas of development, in this review we focus on particular practical aspects of mechanochemistry in order to allow full optimisation of the approach in searches for new solid forms including polymorphs, salts and cocrystals as well as their solvated/hydrated analogues. As a consequence of the apparent experimental simplicity of the method (compared to more traditional protocols e.g. solvent-based methods), the high efficiency and range of conditions available in a mechanochemical screen, mechanochemistry should not be considered simply as an alternative method when other screening methods are not successful, but rather as a key strategy in any fully effective solid form screen providing reduced effort and time as well as the potential of requiring reduced amounts of material.

Keywords: Crystal; Grinding methods; Multicomponent solid; Polymer; Polymorphism; Seeding.