Supercritical CO2 as new pathway for cocrystals – CocrysCO2

Surface control and tailoring nanophase material are topics at the frontiers of fundamental and applied sciences and represent major theoretical issues as well as industrial and economical stakes. In the pharmaceutical sector, a new strategy for modulating the physical and chemical properties of drugs is the formation of cocrystals, i.e. multicomponent assemblies of drug (API) and coformer held together by noncovalent interactions. Meanwhile, the need for improved manufacturing technologies is getting more and more crucial, notably because of the emergence of the generics that are less expansive than the original drugs and of the growing social concerns for environment protection and global changing that motivate the emergence of alternative products and manufacturing routes.
Supercritical technologies have beneficed from the growing consciousness for better, safer products, especially in food and pharmaceutical sectors. As for active powders, literature reports dozens of examples of compounds crystallized by the addition of CO2 to an organic liquor. However, although progresses have been made, empiricism dominates largely in the investigations, preventing from drawing exploitable conclusions regarding mechanism elucidation. Moreover, the ability of supercritical fluids to tune particle size is demonstrated, but tuning crystal habit or form is only an emerging task.
To date, no cocrystalline drug products appear to be in the market, although there is no doubt that cocrystals are present in pharmaceutical drug pipelines. Cocrystal studies pertain mostly to functional group compatibility and/or methods for their preparation, but the presence of hydrogen-bonding is insufficient to predict whether or not a cocrystallization will be successful. In order to move from small scale screening exercises to a viable option for development and ultimately drug products, scalable processes offering high cocrystal purity and yields must be devised and established.
The high potential of cocrystals combined to the need for viable production routes are strategic issues on which CocrysCO2 project is based. Merging crystal science and process engineering, the project focus on cocrystal fabrication in CO2, in a strong objective to develop a knowledge-based engineering approach of such operation. The target is to evaluate a new pathway to create supersaturation or mediated transformation through the addition of compressed CO2 to an initial liquid solution of API and coformer (antisolvent effect). Based on the ability of CO2 to modify thermodynamics and crystallization times, one can expect different structures to be produced. The challenging scientific objective of the project is to understand how phase equilibria, hydrodynamics and kinetics interplay to realize the cocrystal complex preferably over the homoprecipitates, i.e. crystals of individual species. Hence, the three topics will be thoroughly addressed during CocrysCO2, thanks to the highly qualified and complementary consortium.