国产复方克霉唑乳膏体外透皮吸收研究

In vitro transdermal absorption of domestic compound clotrimazole cream

目的建立复方克霉唑乳膏体外透皮吸收测定方法,并以进口克霉唑乳膏作为参比,分析国产乳膏体外透皮差异情况。方法采用离体猪耳背皮肤作为透皮试验材料、30%乙醇-生理盐水为接收液,改良Franz扩散池法考察乳膏在32℃环境下透皮吸收规律,分别以LC-MS/MS法测定接收液中克霉唑吸收量随时间的变化、HPLC法测定试验结束后离体皮肤内克霉唑滞留量。结果3批国产乳膏与进口乳膏透皮量的比值分别为:1.32、1.75、1.62,皮内滞留量的比值分别为:1.19、1.57、1.32,4批乳膏皮内滞留量与透皮吸收总量的比例为88.03%~90.19%,皮内滞留量远高于透过量,符合该类药物临床用药特性,但国产制剂的平均粒径远高于进口制剂。结论国产复方制剂体外透皮性能均高于进口制剂,但不同企业制剂间存在差距,有待进一步优化;新建方法适用于复方克霉唑乳膏体外透皮吸收测定,可为半固体制剂质量评价提供依据,同时为其他复方制剂品种的研发和处方工艺优化提供借鉴。

Objective To determine in vitro transdermal absorption of compound clotrimazole cream,and to analyze the difference of in vitro transdermal absorption of domestic cream with imported clotrimazole cream as reference.Methods The in vitro porcine ear skin was used as the transdermal experimental material,and 30%ethanol-saline was used as the receiving solution.The modified Franz diffusion cell method was used to investigate the transdermal absorption of the cream at 32℃.The changes of drug absorption in receiving liquid with time were determined by LC-MS/MS method,and the drug retention in isolated skin after the experiment was determined by HPLC method.Results The ratio of transdermal amount of three batches of domestic cream to imported cream was 1.32,1.75 and 1.62,respectively,and the ratio of intradermal retention was 1.19,1.57 and 1.32,respectively.The ratio of intradermal retention to total transdermal absorption of four batches of cream was 88.03%~90.19%.The intradermal retention was much higher than the total transdermal absorption,which was in line with the clinical characteristics of these drugs,but the average particle size of domestic preparations was much higher than that of imported preparations.Conclusion The in vitro transdermal performance of domestic compound preparations is higher than that of imported preparations,but there is a gap between different enterprise preparations,which needs to be further optimized.The new method is suitable for the determination of transdermal absorption of compound clotrimazole cream in vitro,which provides a basis for the quality evaluation of semi-solid preparations,and provides reference for the development of other compound preparations and the optimization of prescription process.