Solid–liquid phase equilibrium and ternary phase diagrams of ethenzamide-saccharin cocrystals in different solvents

• The phase diagrams for ethenzamide-saccharin cocrystals were measured.
• The effects of temperature and solvents on the phase diagram were investigated systemically.
• The solubility of ethenzamide-saccharin cocrystals was correlated by using a deduced mathematical model.
• The solubility of ethenzamide-saccharin cocrystals as a function of saccharin concentration was calculated.

The phase equilibrium for ethenzamide (EA) and saccharin (SAC) in ethanol, isopropanol and ethyl acetate were determined at 298.15 and 308.15 K under atmospheric pressure in this work. In ethanol and isopropanol, the two solutes dissolve incongruently and the diagrams are asymmetric, so excessive EA is required to isolate cocrystals. However in ethyl acetate, EA and SAC exhibit similar dissolution behavior, resulting in larger and more symmetric regions for EA-SAC cocrystal, which would be beneficial to enhance the control of EA-SAC cocrystallization process. In addition, the solubility of EA-SAC cocrystal was correlated by using a mathematical model based on both solubility product and solution complexation. The solubility of EA-SAC cocrystal as a function of SAC concentration was calculated. These new findings are of great importance to control the cocrystallization process of EA-SAC.