Caffeine−glutaric acid cocrystal polymorphs, Form I and Form II, are presented as a model system to study cocrystal dissociation under controlled humidity. On the basis of relative humidity (RH) data, it was observed that Form I transforms to Form II at high RH and that the rate of the polymorphic phase transformation increases with increasing RH, with the relative stability of the cocrystal following a trend similar to that of the coformer deliquescence point for other caffeine dicarboxylic acid cocrystals. In addition, reduction in particle size, change in crystal morphology with greater number of crystal faces exposed to surrounding atmosphere, and internal arrangement of molecules in the crystal structure are shown to influence cocrystal instability and favor dissociation under increased humidity.

Liquid-assisted grinding allows the rapid, waste-free and one-pot synthesis of a variety of magnesium drug derivatives directly from the excipient MgO; such reactivity is relevant for the behaviour of ibuprofen formulations involving MgO and can be used for oxide-based mechanosynthesis of metal-organic salts, discrete complexes and carboxylate clusters involving magnesium and pharmaceutically active ingredients.

Here, we highlight recent research involving atomic force microscopy investigations of molecular crystals, and focus particularly on the latest relevant advances in our knowledge of crystal-growth mechanisms and structure-property relationships in organic crystals. This brief survey features the importance of incorporating AFM into solid-state research as an essential tool for the informed design and construction of crystalline materials.

AFM of cocrystals: Atomic force microscopy can be used to observe phase changes at crystal surfaces where the transformation is accompanied by a change in the spacing between layers of molecules. The conversion of a metastable polymorph of the caffeine-glutaric acid cocrystal into the thermodynamically stable form was analyzed continuously in situ using intermittent-contact-mode atomic force microscopy.