Cocrystallization of curcumin with benzenediols and benzenetriols via rapid solvent removal

Abstract

Recent advances in crystal engineering by cocrystallization have offered a promising approach for tackling undesirable physicochemical properties of drug substances. In this study, various structurally similar benezenediols and benezenetriols, namely, catechol (CAT), resorcinol (RES), hydroquinone (HYQ), hydroxyquinol (HXQ), and pyrogallol (PYR), were employed as coformers to obtain phase pure cocrystals with curcumin (CUR) by rapid solvent evaporation of solutions. We successfully prepared two new cocrystals, CUR–CAT and CUR–HYQ, and a new polymorph of cocrystal, CUR–HXQ. Both could not be obtained by traditional cocrystallization methods. Their 1:1 stoichiometry was confirmed by the construction of a binary phase diagram through differential scanning calorimetry analysis. The hygroscopicity, dissolution, and tableting performance of the resulting cocrystals were evaluated. Compared to the individual constituent coformers, cocrystals exhibited profound improvement in the stability against high humidity. The CUR–HXQ cocrystal displayed an intrinsic dissolution rate 7 times faster than CUR. Four out of the five cocrystals had better tabletability. This work demonstrated the effectiveness of discovering cocrystals by kinetic entrapment using a fast solvent removal approach. Some of these cocrystals possess improved pharmaceutical properties for future development of solid dosage forms of CUR.