The Dual Impact of Cocrystal Formers: Contrasting Effects of Diprophylline and Theobromine on the Solid-State Characteristics and In Vivo Pharmacokinetics of Myricetin

Abstract Myricetin (MYR), also known chemically as 3,5,7,3′,4′,5′-hexahydroxyflavone, is abundantly present in traditional Chinese medicine, various fruits, and other medicinal substances. It is a natural compound renowned for its extensive pharmacological activities. Nevertheless, its extremely low water solubility poses a significant challenge to its development and application. Cocrystallization technology emerges as an effective strategy to address this limitation. In this study, two novel cocrystals of MYR with diprophylline (DPL) and theobromine (TB)MYR-DPL−H2O (1:1:1) and MYR-TB (1:1)were successfully synthesized. Their structural characteristics were systematically analyzed, and their stability, hygroscopicity, in vitro dissolution, and in vivo absorption were thoroughly assessed. The findings revealed that both cocrystals demonstrated good stability and reduced the hygroscopicity of MYR. Moreover, the formation of these cocrystals significantly increased the in vitro solubility of MYR. Interestingly, there was a notable discrepancy between the in vitro solubility of MYR cocrystals and their in vivo pharmacokinetic profiles, which suggests an area for further research. As a green and environmentally friendly approach, this crystal engineering technique offers substantial support for improving the physicochemical properties of MYR and enhancing its drugability.