乙酰甲喹溶解度及表观油水分配系数的测定

Determination of equilibrium solubility and apparent oil/water partition coeffi cient of mequindox

目的研究乙酰甲喹在不同p H条件下的平衡溶解度和表观油水分配系数(Ko/w),为乙酰甲喹新剂型的开发提供理论基础。方法配制不同p H值的磷酸盐缓冲液,采用饱和法测定其平衡溶解度;通过乙酰甲喹在油相(正辛醇)和水相的分配平衡浓度比,计算油水分配系数。结果乙酰甲喹在不同p H条件下的溶解度均为微溶,都在3.500mg/m L左右,且无显著差异;该药物在不同p H磷酸盐缓冲液中的油水分配系数均较大,在p H=6.0时油水分配系数为2.315。结论溶解度是限制乙酰甲喹临床疗效的主要因素,通过加入表面活性剂等方式来改善乙酰甲喹的溶解度是提高该药物生物利用度的主要方式。

Objective To determine the equilibrium solubility and the apparent partition coefficient of mequindox in a series of phosphate buffer solution of different pH so as to provide a basic study for the exploitation of mequindox preparation.Methods A series of buffer solutions of different pH were prepared.The equilibrium solubility was determined by saturation method.The apparent partition coefficient was calculated with concentration ratio of mequindox in n-octanol and water pHase after partition equilibrium.Results mequindox was slightly soluble in different pH buffer solution,its equilibrium solubility is 3.500mg/mL or so,and there is no significant difference in different pH conditions.The apparent oil/water partition coefficient of mequindox was large in different pH,the biggest apparent oil/water partition coefficient was 2.315 at pH6.0.Conclusions Equilibrium solubility is the major factor which limits the clinical efficacy of mequindox.Improving equilibrium solubility of mequindox by adding surfactants or any other approaches is the main way to increase its bioavailability.