A Study on the Synergistic Cocrystallization of Chemically Related Curcuminoids with Hydroxybenzenes

Cocrystallization of the curcuminoids (CURDs) curcumin (CUR), demethoxycurcumin (DMC), and bis(demethoxy)curcumin (BDMC) with the coformers resorcinol (RES) and hydroxyquinol (HYQ) from solution was investigated toward its potential of being used as a synergistic separation technique of the CURDs from their ternary mixtures. Therefore, solubilities of single CURDs with the respective coformer in toluene-ethyl acetate 90/10 v/v at 25 °C were measured, and ternary phase diagrams were constructed. CUR·RES and BDMC·HYQ cocrystals were identified, revealing an incongruent solubility behavior. All other CURD-coformer systems showed eutectic behavior. Separation experiments were performed using a CUR-rich and almost equimolar CURD mixture. Solubility measurements of CURD mixtures revealed large influences on each other’s solubility and high potential of DMC being integrated into CUR crystals and cocrystals. Cocrystallization of CUR·RES from the CUR-rich mixture outperformed direct CUR crystallization. In the case of BDMC·HYQ, the presence of the other CURDs suppressed cocrystal formation. Using the universal cocrystal solubility product Ks, CUR·RES cocrystal solubilities were predicted in ethanol, a solvent exhibiting large solubility differences between CUR and other CURDs. Subsequent separation experiments showed no benefit of cocrystallization over direct CUR crystallization.