Hesperidin is a rutinoside of flavanone type with relevant therapeutic properties but poor water solubility which limits its therapeutic applicability. However, cyclodextrins (CDs) have been successfully used as drug carriers to enhance the solubility of several drugs, to improve their bioavailability, and therapeutic efficacy. We report herein the formation of inclusion complexes of β-cyclodextrin and hesperidin through the green approaches mechanochemistry and supercritical fluid and compare these results versus the classical lyophilization method. The resulting stoichiometries and the specific interactions of the complexes were analyzed by NMR, UV, and mass spectrometry. The β-cyclodextrin and hesperidin inclusion complex (IC) successfully obtained through green methodologies demonstrated superior levels of flavonoid content. In terms of solubility, the mechanochemistry inclusion complex showed the best improvement in solubility. We demonstrate herein that the use of green methodologies such as supercritical fluids and mechanochemistry are useful alternatives to the conventional method of lyophilization, to improve the solubility of β-cyclodextrin IC.

中文翻译：

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β-环糊精-橙皮苷包合物的机械化学和超临界流体合成：绿色化学与冻干的比较


橙皮苷是一种黄烷酮型芸香苷，具有相关的治疗特性，但水溶性差，限制了其治疗适用性。然而，环糊精 （CD） 已成功用作药物载体，以增强多种药物的溶解度，提高其生物利用度和治疗效果。我们在此报告了通过绿色方法机械化学和超临界流体形成 β-环糊精和橙皮苷包合物，并将这些结果与经典的冻干方法进行比较。通过 NMR、UV 和质谱分析所得的化学计量和复合物的特定相互作用。通过绿色方法成功获得的 β-环糊精和橙皮苷包合物 （IC） 显示出高水平的类黄酮含量。在溶解度方面，机械化学夹杂物复合物的溶解度改善最好。我们在此证明，使用绿色方法（如超临界流体和机械化学）是传统冻干方法的有用替代方案，可以提高β-环糊精 IC 的溶解度。