蒙花苷溶解度及油水分配系数的研究

Determination of solubility and oil-water partition coefficient of linarin

目的测定蒙花苷的溶解度及油水分配系数,为药物成药性评价及剂型设计提供依据。方法采用HPLC法测定蒙花苷在不同有机溶剂及不同pH值缓冲盐溶液中的平衡溶解度,并测定蒙花苷在高分子材料和表面活性剂中的溶解度;利用Molinspiration软件对蒙花苷的油水分配系数进行预测,并采用摇瓶-HPLC法测定药物在正辛醇-水、正辛醇-缓冲液体系中的表观油水分配系数。结果蒙花苷在水中的平衡溶解度为0.059μg/mL,在碱性溶液中的溶解度有所增加;高分子材料和表面活性剂均可增加蒙花苷的溶解度,其中HP-β-CD的增溶作用最强,可增加214.6倍;lg蒙花苷在正辛醇-水、正辛醇-缓冲盐溶液中的P值在0.50～1.04,与计算机预测值0.513一致。结论蒙花苷不溶于水,脂溶性差,通过添加辅料,其溶解性有所提高。

Objective To establish a method for determination of solubility and oil-water partition coefficient of linarin, and to provide the basis for drug evaluation and dosage form design. Methods Equilibrium solubilities were determined by HPLC method in different organic solvents and different pH buffer solution systems; Also the solubilities of linarin in certain macromolecules and surfactant were measured; Molinspiration software was used to forecast the oil-water partition coefficient of linarin, and the partition coefficients of linarin in n-octanol-water/buffer solution systems were measured by shake flask-HPLC method. Results The equilibrium solubility of linarin in water was 0.059μg/mL, which was lower than that in alkaline solution; Certain macromolecules and surfactant could increase the solubility of linarin, especially HP-β-CD with 214.6-fold increase; The octanol-water partition coefficient of linarin was between 0.50 and 1.04, consistent with the computer predicted 0.513. Conclusion Linarin is insoluble in water, and poor fat-soluble, but its solubility could be imoroved by adding accessories.