双氯芬酸依泊胺凝胶的体外透皮吸收研究

Penetration study of Diclofenac epolamine gel in vitro

目的采用HPLC测定体外透皮接收液中双氯芬酸依泊胺的含量,并研究4种不同处方双氯芬酸依泊胺凝胶的体外透皮能力。方法采用Kromasil C8（250 mm×4.6 mm,5μm）色谱柱,以甲醇-0.12%冰醋酸溶液（80∶20）为流动相,流速为1.0 mL·min^-1,检测波长为276 nm。体外透皮实验采用Franz扩散池,以实验用离体乳猪皮为透皮屏障,分别在不同时间点取样测定透皮接收液中双氯芬酸依泊胺的浓度,计算累积透皮量。结果双氯芬酸依泊胺的标准曲线方程为：A=32.950C-2.1203（r=0.9997）,双氯芬酸依泊胺30.60～76.50μg·mL^-1与峰面积的线性关系良好,平均回收率为99.67%。4种处方（3%、5%、8%、10%大豆磷酯）的累积透皮吸收量与时间呈良好的线性关系,10%大豆磷酯凝胶处方与市售凝胶的体外透皮过程相似,两者的透皮结果无明显差异。结论所用方法操作简便,快速准确,是考察双氯芬酸依泊胺凝胶体外透皮能力的理想方法。

OBJECTIVE To establish an HPLC method for the quantitative determination of Diclofenac epolamine gel in percutane- ous solution in vitro, and investigate the in vitro percutaneous penetration ability of Diclofenac epolamine gel of four different formula- tions. METHODS A Kromasil Cs （250 mm× 4.6 mm, 5 mm） column was used with mobile phase consisting of methanol - 0.12% acetic acid（80 ： 20）. The flow rate was 1.0 mL·min^-1. The detection wavelength was 276 nm. The in vitro permeation experiments were performed using improved Franz type diffusion cells. The excised minipig＇ s skin was used as a transdermal barrier. The concentra- tion of Diclofenae epolamine in the receptor solution was determined by the mentioned HPLC method to investigate the cumulative permeation quantities of the trial preparation at the different time points respectively. RESULTS The regression equation of diclofenac epolamine was linear in the range of 30.60 - 76.50 μg·mL^-1 （A = 32. 950C - 2. 1203, r = 0. 9997 ）. The average recovery was 99. 67%. A good linear relationship existed between the cumulative penetration quantities and the time of the four formulation（ 3%, 5% ,8% , 10% soybean phospholipids）. And there was only 10% soybean phospholipids formulation had no significant difference in the skin permeation quantities with the commercial gel. CONCLUSION The method is simple, rapid, and accurate. It is a good method to evaluate the ability of permeation in vitro for Diclofenac epolamine gel.