黄芩苷-盐酸小檗碱复合物的溶解度与油水分配系数测定

Determination of Equilibrium Solubility and Oil-water Partition Coefficient of Baicalin-berberine Hydrochloride Complex

目的:测定黄芩苷-盐酸小檗碱复合物的平衡溶解度与油水分配系数,为相关制剂研究奠定基础。方法:建立HPLC分别测定盐酸小檗碱和黄芩苷含量,PntulipsTMBP-C18色谱柱(4.6 mm×250 mm,5μm),流动相乙腈-0.2%磷酸水溶液(30∶70),检测波长230 nm,流速1 m L·min^(-1),柱温30℃。采用摇瓶法测定黄芩苷-盐酸小檗碱复合物在水、不同p H介质中的平衡溶解度;测定该复合物在正辛醇-水中的浓度并计算油水分配系数。结果:在p H 6.8~8.0的介质中,复合物中黄芩苷和盐酸小檗碱的溶解度与原药相比分别降低了50,2倍左右;复合物中黄芩苷和盐酸小檗碱的油水分配系数分别为0.109和0.399,分别较原药提高了2.37,4.69倍。结论:黄芩苷-盐酸小檗碱复合物的溶解度和油水分配系数与原药存在差异,可能会影响药物的体内行为和口服给药后的胃肠道吸收情况。

Objective： To determine the equilibrium solubility and the oil-water partition coefficient of baicalin-berberine hydrochloride complex for further study on the related preparations. Method： HPLC was validated for analysis of berberine hydrochloride and baicalin. The equilibrium solubilities of baicalin-berberine hydrochloride complex in water and media with different pH were measured by shaking flask method. The concentration of this complex in n-octanol and water was determined to calculate the oil-water partition coefficient. Result： The solubilities of berberine hydrochloride and baicalin in the complex were 2-fold and 50-fold lower than that of crude drugs in medium with pH of 6.8-8.0. The oil-water partition coefficients of baicalin and berberine hydrochloride in the complex were 2. 37 times and 4. 69 times higher than that of the pure drugs, respectively. Conclusion： hydroehloride the complex. Differences of solubility and partition coefficient are revealed between baicalin-berberine complex and pure drugs, which may affect the in vivo performance and gastrointestinal absorption of