Salt Cocrystallization-A Method to Improve Solubility and Bioavailability of Dihydromyricetin

盐共结晶法——一种提高二氢杨梅素溶解度和生物利用度的方法

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Abstract

Objectives: This study aimed to find salts with similar pharmacological effects designed as cocrystals to improve the aqueous solubility and bioavailability of dihydromyricetin (DMY). Methods: A salt-cocrystal solvate (DMY-CIP·C(2)H(6)O) of dihydromyricetin and ciprofloxacin hydrochloride (CIP) was successfully prepared via solvent evaporation method, and further characterized using powder X-ray diffraction, thermal analysis, and infrared spectroscopy. The solubility, stability, bioavailability, and in vitro antimicrobial efficacy of the cocrystal were also studied. Results: The cocrystal could increase the solubility of DMY in water and greatly improve the absorption of DMY in vivo (8-fold enhancement in relative bioavailability). In addition, the in vitro antimicrobial efficacy of the cocrystal was comparable to that of CIP, which is a great improvement for DMY. However, due to the formation of cocrystals with salts, the humidity stability of DMY is reduced and it should not be stored in high-humidity environments. Conclusions: These findings demonstrate that cocrystallization with water-soluble salts represents an effective strategy for optimizing the pharmaceutical properties of poorly soluble compounds.

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