Improving the Poor Aqueous Solubility of Nutraceutical Compound Pterostilbene through Cocrystal Formation

Abstract

Pterostilbene is a nutraceutical compound being investigated for its ability to form cocrystals with pharmaceutically acceptable coformers to improve its poor aqueous solubility. Cocrystals of a 2:1 and 1:1 stoichiometric molar ratio of pterostilbene with piperazine or glutaric acid were synthesized on a multigram scale and fully characterized including single-crystal X-ray diffraction. Furthermore, both cocrystals were evaluated for physical stability with respect to humidity and temperature as well as kinetic solubility. Each cocrystal displayed remarkable stability, showing no evidence of dissociation across a range of durations, temperatures, and relative humidities. The aqueous concentration of pterostilbene measured over five hours from dissolution of the pterostilbene-piperazine cocrystal was six times higher than the solubility of the single-component pterostilbene. Although X-ray powder diffraction results indicate partial transformation of the pterostilbene-piperazine cocrystal to pterostilbene after 5 h, this increase in concentration was sustained throughout the dissolution experiment. Within 5 min of slurrying the pterostilbene-glutaric acid cocrystal in water, precipitation of pterostilbene was observed; thus no dissolution data under these conditions were obtained.