摘要
Aim To investigate the combined effect of hydroxypropyl-β-cyclodextrin （HP-β-CD） and media pH on the solubility of prostaglandin E1 （PGE1） and construct a theoretical equation for the drug solubility as a function of HP-β-CD concentration and media pH. Methods The solubility of PGE1 under different pH conditions was determined. Then, the drug solubility in different concentrations of HP-β-CD acidic or pH neutral solutions was measured, respectively. Finally, a theoretical solubility equation for the drug as a function of HP-β-CD concentration and media pH was deduced and confirmed in experiment. Results PGEs was solubilized by HP-β-CD or by increasing media pH. The drug solubility as a function of HP-β-CD concentration was found to follow the AL-type complexation model in acidic or neutral pH media, suggesting that both the ionized and neutral drugs form 1：1 molecular ratio complexes. Conclusions The solubility of PGE1 may be improved by increasing media pH or by using HP-β-CD as a solubilizer. HP-β-CD and media pH can produce combined effect on the solubility of PGE1. The deduced equation for the drug solubility in this study effectively characterizes the roles of HP-β-CD and media pH in determining total solubility of the drug.
目的研究羟丙基-β-环糊精(HP-β-CD)与介质pH值对前列腺素E1(PGE1)溶解度的综合影响并进一步推导出该药物溶解度的理论方程。方法首先测定药物在不同pH值水中的溶解度;然后分别测定在酸性及中性系列浓度的HP-β-CD溶液中,药物的溶解度;最后推导出以HP-β-CD与介质pH值为变量的药物溶解度方程并对其合理性进行验证。结果溶解度测定结果表明,提高介质的pH值或以HP-β-CD为增溶剂,均可增加PGE1的溶解度。分子型药物或离子型药物与HP-β-CD测得的相溶解度图均为典型的AL型,提示药物结构上的五元碳环部分已嵌入HP-β-CD的疏水性孔穴中,从而形成1:1摩尔比包合物。结论以HP-β-CD作为增溶剂,同时提高介质的pH值,可对PGE1的溶解度产生协同增加效应。本研究中导出的PGE1溶解度方程,可有效表征HP-β-CD与介质pH值二者对该药物溶解度的综合影响。
