盐酸普罗帕酮包合物的制备及其性质研究

Preparation and characteristics of propafenone hydrochloride inclusion complex

目的:制备盐酸普罗帕酮包合物并研究其理化性质和吸收性质。方法:以β-CD为包合材料,用研磨法制备包合物,以原料药盐酸普罗帕酮为对照,进行溶解度、溶出速率、热分析和显微观察法分析。通过大鼠单向灌流模型,采用HPLC测定药物浓度,比较在相同浓度下盐酸普罗帕酮和包合物在不同肠段的吸收速率常数。结果:经多种方法验证,确证形成了包合物,与原料药相比,包合物的溶解度提高了3.75倍,吸收速率常数也有显著性差异。结论:制备包合物的方法简单可行,且制备出的包合物可以显著提高药物的溶解度和吸收。

Objective： To prepare propafenone hydrochloride inclusion complex, and to investigate its physicochemical and absorption characteristics. Methods： β-CD was used as the wall material. The inclusion complex was prepared by grinding PPF and β-CD （1：1 in tool）. Then, various methods, including solubility, dissolution rate, DSC and microscopy, were used to determine difference in physical and chemical aspects between PPF and β-CD. The single-pass perfusion was used to investigate intestinal absorption character in rats. The absorption rate constants （Ka） of PPF and inclusion complex were compared in the same concentration of propafenone in intestinal fluid, which was analyzed by HPLC. Results： The inclusion complex was successfully formed by grinding according to the results of analyses. The solubility of inclusion complex was 3.75 times more than that of PPF. Absorption rate constant （Ka） of inclusion complex was also significantly different from that of PPF. Conclusion： The solubility and absorption of PPF can be significantly increased in the inclusion complex, and the preparation through grinding method is easy and practical.