Solid–Liquid Phase Equilibrium and Ternary Phase Diagrams of Ibuprofen–Nicotinamide Cocrystals in Ethanol and Ethanol/Water Mixtures at (298.15 and 313.15) K

The phase diagrams for ibuprofen (IBU) and nicotinamide (NCT) in both ethanol and ethanol/water mixtures were constructed at (298.15 and 313.15) K under atmospheric pressure using static method. It is revealed that employing solvent mixtures in cocrystallization could significantly affect the symmetry of phase diagrams. In pure ethanol, the two solutes dissolve incongruently and the diagrams are asymmetric, so excessive IBU is needed to isolate cocrystals. However, in ethanol/water mixtures (mass fraction of water was 0.30), the solubility difference between the two components can be leveled out, resulting in more symmetric phase diagrams which can enlarge the processing space for cocrystallization. The solubility of the 1:1 IBU–NCT cocrystal was evaluated as a function of NCT concentration based on the solubility product. These findings are of great importance to develop the cocrystallization process for manufacturing IBU–NCT cocrystal.