Limits of the Co-crystal Concept and Beyond

Abstract

In this chapter, views of co-crystals are broadened. Indeed, any classification has its limits and, clearly, the thermodynamics of heterogeneous equilibria can help to replace the concept of the co-crystal in a more general perspective. Co-crystals are nothing other than intermediate compounds. Nevertheless, the concept suffers from intrinsic uncertainties due to the numerous situations in which they can occur such as the continuum between solvate and co-crystals, hybrid salt-co-crystals, multi-epitaxy and so on. It is even possible to find the same partners with simultaneously salt-like and co-crystal-like relationships in a given crystal structure. Therefore, rather than creating questionable terms and maintaining endless semantic debates with poor added value, the scientific community should concentrate more on the three long lasting problems related to intermediate compounds listed below: 1. Prediction of intermediate compounds: indeed, apart from statistical trends (e.g. racemic compounds as detailed in this chapter), there is no way to predict the existence of an intermediate compound with acceptable reliability. 2. Prediction of the attributes of these intermediate compounds: to date the connection between structures and properties is very weak despite the evident interest. 3. How to design a process to obtain those intermediate phases with a good yield and minimum side products? Moreover these processes should fulfil the specifications for the final products such as crystallinity, crystal size distribution, morphology, and so on. These questions are really meaningful from an industrial perspective and for advancing knowledge in the organic solid state.

Cocrystals to facilitate delivery of poorly soluble compounds beyond-rule-of-5

“…Basic concepts of crystallization can be applied to understand and control the nucleation and growth of cocrystals. For an in-depth description of cocrystallization mechanisms and methods, readers are referred to other publications [48–52]. Here we summarize the main principles that guide cocrystal formation.…”

A Possible Infinite Number of Components in a Single Crystalline Phase: On the Isomorphism of Brivaracetam–Guest Molecules

“…Indeed, the same crystalline phase (Phase 2) can be considered as a clathrate (with guest being a gas at ambient temperature), a solvate (with guests which are liquid at ambient temperature), or a cocrystal (with guests that are solid at ambient temperature), and thus it puts into question the consistent character of such classification . The term “intermediate non-stoichiometric compound”, related to a thermodynamic description of matter, may be preferred to avoid those problems …”

Discovery of New Proxyphylline-Based Chiral Cocrystals: Solid State Landscape and Dehydration Mechanism

“…To the best of our knowledge, no cocrystal of PXL has ever been reported in the literature. The present paper describes the discovery of new cocrystals , and the study of the related solid-state landscape with the help of dedicated experimental methods.…”