Discovering New Co-Crystals

Abstract

A new and systematic method for co-crystal screening has been developed, based on improvements in the understanding of the thermodynamic factors that influence co-crystal formation. This method works from the premise that pure component solubilities determine the concentration regions to screen for new co-crystals, rather than the stoichiometry of the co-crystal. An extended phase diagram screen gives the composition ranges in which the co-crystal is the stable crystalline form. The method is based on the measurement of saturation temperatures which are experimentally easily accessible using standard laboratory equipment. The method has been validated using both carbamazepine and cinnamic acid with a number of co-formers in ethanol solvent. New co-crystals of carbamazepine with isonicotinamide, benzamide and 3-nitrobenzamide, and of cinnamic acid with 3-nitrobenzamide have been discovered.