Crystallization reactions are depicted using pathways in phase diagrams. This approach used is rational both in seeding and control of the process.

The mirror symmetry relationship between enantiomers makes their separations by ‘classical’ separation methods difficult. When applicable, preferential crystallization is a productive and cost effective process which consists of alternate crystallizations of both enantiomers crystallizing as a conglomerate. Addition of in situ racemization to ‘classical’ preferential crystallization allows the yield to increase up to 100% in a single batch operation. Furthermore, the implementation of continuous ‘gentle’ grinding can solve the main problem of this method, i.e. the nucleation of the counter enantiomer. Preferential crystallization methodology can be also applied to any system composed of non symmetrical species. However, a set of thermodynamic and kinetic parameters must be determined for every compound that is supposed to crystallize selectively. This ‘highlight’ details the basic principles and the limitations of ‘classical’ preferential crystallization and its applications on ‘exotic’ systems by an extensive usage of phase diagrams.

Cocrystallization has been promoted as an attractive early development tool as it can change the physicochemical properties of a target compound and possibly enable the purification of single enantiomers from racemic compounds. In general, the identification of adequate cocrystallization candidates (or coformers) is troublesome and hampers the exploration of the solid-state landscape. For this reason, several computational tools have been introduced over the last two decades. In this study, cocrystals of Praziquantel (PZQ), an anthelmintic drug used to treat schistosomiasis, are predicted with network-based link prediction and experimentally explored. Single crystals of 12 experimental cocrystal indications were grown and subjected to a structural analysis with single-crystal X-ray diffraction. This case study illustrates the power of the link-prediction approach and its ability to suggest a diverse set of new coformer candidates for a target compound when starting from only a limited number of known cocrystals.