Nutraceutical cocrystals: utilizing pterostilbene as a cocrystal formerElectronic supplementary information (ESI) available: TGA and DSC thermograms of 1-3, XRPD patterns after % RH stress experiments, and XRPD patterns after solubility experiments. CCDC reference numbers 764871-764873. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c002045a

The nutraceutical compound pterostilbene is investigated for its propensity to form cocrystalline materials with active pharmaceutical ingredients. Three cocrystals of a 1 : 1 stoichiometric molar ratio of pterostilbene with caffeine (two polymorphs, Form I and Form II) and carbamazepine were prepared and characterized by crystallographic (XRPD, single-crystal) and thermoanalytical (TGA, DSC) techniques. Physical stability of the cocrystals with respect to relative humidity (RH) was examined and found to be dramatically improved in relationship to caffeine or carbamazepine. The carbamazepine : pterostilbene cocrystal was stable upon slurrying in water for 3 days; therefore, aqueous equilibrium solubility measurements were carried out, revealing that the cocrystal solubility was 7× lower than carbamazepine dihydrate and 2.5× lower than pterostilbene. Slurrying the caffeine : pterostilbene cocrystal (Form I) in water led to a solution that was supersaturated with respect to pterostilbene, resulting in the precipitation of pterostilbene after three days; therefore concentrations at specific time points were measured as opposed to equilibrium solubility. At five hours the concentration of the caffeine cocrystal was 33× lower than the caffeine hydrate solubility, but was 27× higher than the pterostilbene solubility. Pterostilbene, a nutraceutical compound and methylated analog of resveratrol, was cocrystallized with active pharmaceutical ingredients, in which the caffeine : pterostilbene cocrystal lead to a 27-fold increase in pterostilbene solubility.