流通池法测定复方酮康唑乳膏释放度的方法研究

Dissolution study of compound ketoconazole cream using flow-through cell method

目的:建立适用于复方酮康唑乳膏的释放度检查方法。方法:采用流通池法测定复方酮康唑乳膏的释放度,释放介质为0.01 mol·L^(-1)盐酸溶液,流速为8 mL·min^(-1);以 HPLC 测定释放量,使用 Symmetry C_(18)柱(3.9 mm×150 mm,5 μm),流动相0.02 mol·L^(-1)磷酸氢二钠溶液-甲醇(25:75,用磷酸调节 pH 至6.9±0.1),流速1 mL·min^(-1);检测波长为225 nm。结果:酮康唑在0.3～18μg·mL^(-1)浓度范围内线性良好(r=0.9999);平均回收率(n=9)为99.8%,RSD 为0.67%。同一厂家的复方酮康唑乳膏释放曲线稳定,在24 h 内释放药物超过65%;不同厂家的复方酮康唑乳膏释放曲线不同。结论:本方法可用于复方酮康唑乳膏的释放度检查,对于药物乳膏的质量控制具有指导意义。

Objective：To develop a method for the dissolution test of compound ketoconazole cream. Method：Flow -through cell method was adopted to test the dissolution of compound ketoconazole cream, with 0. 01 mol · L^-1 hydrochloric acid solution as the dissolution medium, at the flow speed of 8 mL · min^-1. An HPLC method was employed to determine the content of ketoconazole, with the mobile phase of 0. 02 mol· L^-1 sodium dihydrogen phosphate solution -methanol（25：75 ,adjusted pH to 6. 9 ±0. 1 with phosphoric acid） at a flow rate of 1 mL · min^-1, on a column of Symmetry C18 （3.9 mm × 150 mm,5 μm） at the detection wavelength of 225 nm. Results：The linear range of ketoconazole was 0. 3 - 18 μg · mL^ - 1 （ r = 0. 9999）, and the average recovery （ n = 9） was 99.8 % （ RSD = 0. 67% ）. More than 65% of labelled amount of ketoconazole was dissolved at the time of 24 h for one manufacture products, and there is a difference release profile between products from different manufactures. Conclusion：This method can be used to test the dissolution of compound ketoconazole cream, and give an example in the quality control of cream.