大黄酸平衡溶解度和油水分配系数的测定

Determination of Equilibrium Solubility and Apparent Oil/water Partition Coefficients of Rhein

目的测定大黄酸在不同溶剂中的平衡溶解度及表观油水分配系数,为大黄酸新剂型的设计提供参考依据。方法采用高效液相色谱法测定大黄酸在水、不同p H值缓冲液、不同溶剂中的溶解度;采用经典摇瓶法测定大黄酸在正辛醇缓冲液中的表观油水分配系数。结果 37℃时大黄酸在水中的平衡溶解度为3.89μg·m L^(-1),表观油水分配系数(lgP)为2.79;大黄酸的溶解度在随着p H值的升高呈现增加的趋势,在p H值6.8和7.4的磷酸盐缓冲液中分别达362.20和431.65μg·m L^(-1)。大黄酸在半极性溶剂中溶解度相对较好,特别是在聚乙二醇400中的溶解度可达2 971.74μg·m L^(-1)。大黄酸的油水分配系数随p H值的升高而下降,在p H值6.8和7.4的磷酸盐缓冲液中分别为0.83和0.54。结论大黄酸水溶性差,增大p H值可增加其溶解度,但油水分配系数随之降低。

ObjectiveTo determine the solubility of rhein in different vehicles and its partition coefficients in the n octanol water system for designing new formulations.MethodsHigh performance liquid chromatography(HPLC)method was established to determine the concentration of rhein in water,different pH solutions and different solvents;the partition coefficients for the n octanol buffer solution systems were determined by shaking flask method.ResultsThe equilibrium solubility of Rhein was3.89μg·mL-1and the lgP was2.79in water at37℃.The solubility of rhein was increased with the raise of pH,which could reach362.20and431.65μg·mL-1in phosphate buffer solution at pH6.8and7.4,respectively.Solubility of rhein in the semi polar solvent was relatively good,which can up to2971.74μg·mL-1in PEG400.The oil water partition coefficients of rhein were decreased with the increase of pH,and were0.83and0.54in phosphate buffer solution at pH6.8and7.4,respectively.ConclusionRhein is almost not soluble in water.With the raise of pH,the solubility is increased but the oil water partition coefficient is decreased.