Rational Coformer Selection and the Development of New Crystalline Multicomponent Forms of Resveratrol with Enhanced Water Solubility

We report the development of 10 new cocrystal forms of the nutraceutical compound resveratrol obtained through a rational coformer screening by utilizing the interaction site pairing energy differences computed based on molecular electrostatic potential calculations. A new monohydrate form of resveratrol and 10 novel cocrystals with 9 different coformers were characterized in the study. Among the newly developed solid forms of resveratrol, two of its cocrystals with (1) a Generally Recognized As Safe compound piperazine and (2) the bioactive compound methenamine were subjected to aqueous solubility determination. The newly developed piperazine cocrystal exhibits the highest aqueous solubility among the previously known cocrystals of resveratrol.