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目的:测定异鼠李素在水及正辛醇中的溶解度,计算热力学参数,为异鼠李素剂型设计与体内过程预测提供依据。方法:采用HPLC测定不同温度下异鼠李素在水、正辛醇中的平衡溶解度,测定常温下该成分在正辛醇-水中的表观油水分配系数,流动相甲醇-0.1%甲酸水溶液(70∶30),检测波长370 nm。结果:异鼠李素水溶性差,易溶于正辛醇中,采用Apelblat经典模型对异鼠李素溶解度数据进行拟合,在水、正辛醇中的溶解度拟合方程为lnx_(cal)=879.18-53 895.05/T-126.30ln T(r=0.999 7),lnx_(cal)=-1.32-2 699.36/T+0.35lnT(r=0.999 8),表明该模型拟合结果与实验数据吻合良好。异鼠李素在水和正辛醇中的溶解过程均为吸热和熵增加的过程,常温下异鼠李素的表观油水分配系数P为5 163(lgP=3.71)。结论:异鼠李素为脂易溶性化合物,水溶性较差,通过优化制剂工艺等方法增加其水溶解度可能会提高其口服吸收效率及生物利用度。
OBJECTIVE: To determine the solubility of isorhamnetin in water and n-octanol, and calculate the thermodynamic parameters to provide the basis for isorhamnetin-based formulation design and in vivo process prediction. Methods: The equilibrium solubility of isorhamnetin in water and n-octanol at different temperatures was determined by HPLC. The apparent oil-water partition coefficient of this component in n-octanol-water was determined at room temperature. The mobile phase was methanol-0.1% formic acid aqueous solution 70:30), detection wavelength 370 nm. Results: Isorhamnetin was poorly water-soluble and easily soluble in n-octanol. The solubility data of isorhamnetin were fitted by classical Apelblat model. The solubility equation in water and n-octanol was lnx_ (cal) = 879.18-53 895.05 / T-126.30ln T (r = 0.999 7), lnx_ (cal) = -1.332-2 699.36 / T +0.35lnT (r = 0.999 8), which shows that the model fitting result is in good agreement with the experimental data . The process of isorhamnetin dissolution in water and n-octanol was both endothermic and entropy increasing. The apparent oil-water partition coefficient P of isorhamnetin was 5 163 (lgP = 3.71) at room temperature. CONCLUSION: Isorhamnetin is a lipid-soluble compound with poor water-solubility. Increasing the water solubility of the isorhamnetin may increase its oral absorption efficiency and bioavailability.