格列吡嗪与羟丙基-β-环糊精在溶液中包结作用研究

The Study of the Thermodynamics of the Complexation of Hydroxypropyl-β-Cyclodextrin with Glipizide in the Solution

本文采用相溶解度法测定了不同温度下羟丙基-β-环糊精与格列吡嗪在7.4的磷酸缓冲溶液中形成包结物的稳定常数,进而测定了包结过程的热力学参数。根据测得的热力学参数,讨论了羟丙基-β-环糊精与格列吡嗪包结时范德华力、疏水作用、氢键以及从羟丙基-β-环糊精空穴释放高能水几种弱相互作用力对包结过程的影响。研究结果表明,羟丙基-β-环糊精与格列吡嗪可形成1∶1的可溶性包结物,相溶解度呈AL型;羟丙基-β-环糊精与格列吡嗪在溶液中的包结过程,可以自发的进行(ΔG<0),且为放热反应(ΔH<0),同时也是熵减的过程(ΔS<0)。在羟丙基-β-环糊精与格列吡嗪包结过程中从HP-β-CD空穴释放的高能水、氢键和范德华力起了重要作用。

The phase solubility methods are performed in the buffered aqueous solution at 25-40℃ to give the stability constants and thermodynamic parameters （AG, AH, AS） of the complex system formed by hydroxypropyl--β--cyclodextrin （HP--β-CD） with Glipizide （GZ）. All the phase solubility diagrams show a typical AL--type at various temperatures, suggesting the formation of a soluble complex of the molar ratio of 1 ： 1. The contributions of the several weak forces working between HP --β--CD and GZ are discussed from the viewpoint of thermodynamics, which include Van der Waals＇ forces, hydrogen bonding, hydrophobic interactions and the release of high energy water molecules from HP--β-CD cavity. The thermodynamic parameters obtained indicate that the complexation could proceed spontaneously along with the release of heat and the decrease of entropy, which further proves the important roles of the Van der Waals＇ forces, hydrogen bonds and the release of high energy water molecules from HP--β--CD cavity in the formation of complexation between HP--β--CD and GZ.