Progress in co-crystallization as a separation technology

The separation of small organic molecules by co-crystallization technology, especially the separation of some high-purity APIs that cannot be salted, is the frontier of crystal engineering applications. The principle is to form cocrystal by intermolecular recognition, and to change the lattice energy or solubility characteristics of the target molecule, thereby achieving separation. Aiming at the application of cocrystallization in separation, this paper systematically reviews the examples of co-crystallization in separation and purification of achiral molecules and chiral APIs and intermediates from the thermodynamic principle of cocrystal separation. Separation examples are analyzed from different perspectives such as molecular structure, intermolecular interaction force, solubility product constant, solvent system, etc. For the existing problems of this technology, such as the lack of regularity in the choice of cocrystal formation, the complexity of the actual API purification system, the feasibility of recycling eutectic formation, it is pointed out that establishing the cocrystal formation selection method of the system and in-depth study of thermodynamic behavior are the main research directions in the future. © 2020, Chemical Industry Press. All right reserved.