Thermodynamic Modeling for Efficient Cocrystal Formation

The purpose of this work is to increase the efficiency of the cocrystal formation process by thermodynamic modeling using perturbed-chain statistical associating fluid theory (PC-SAFT). By accounting for the thermodynamic nonideality of the components in the cocrystal system, PC-SAFT is able to model and predict the solubility behavior Of pharmaceutical cocrystals based solely on the knowledge of a single cocrystal solubility point in any solvent and at any temperature. Furthermore, the cocrystal solubility in other solvents and for other temperatures can be predicted without the need for additional measurements. The (+)-mandelic acid/(-)-mandelic acid (1:1), caffeine/glutaric acid (1:1), and carbamazepine/nicotinamide (1:1) cocrystal systems were modeled, and the results were in excellent agreement with the experimental data.