EVAc膜及促进剂对左炔诺孕酮人皮肤渗透速率的影响

 目的：测定不同厚度、不同醋酸乙烯(VAc)含量的乙烯-醋酸乙烯控释膜(EVAc)及不同促进剂对左炔诺孕酮(LNG)人皮肤渗透速率的影响。方法：采用Valia-Chien渗透池与HPLC测定以上不同条件下LNG/体积分数为70%的乙醇(EtOH)饱和液中LNG人皮肤渗透速率。结果：LNG的皮肤/膜渗透速率随控释膜厚度的增加而减少，控释膜厚度的倒数与LNG皮肤渗透速率呈良好的线性关系，皂0.9929。控释膜中VAc含量(280,180,140g·kg^-1)会影响LNG的渗透速率 ，以280g·kg^-1VAc为最高，140g·kg^-1VAc最低。促进剂(20g·kg^-1油酸或20g·kg^-1月桂氮-酮)能明显增加LNG的人皮肤渗透速率。结论：以20g·kg^-1油酸为促进剂,50μm,280g·kg^-1VAc的EVAc膜为控释膜时，LNG人皮肤渗透速率可达设计要求。

Effects of EVAc membrane and enhancers on levonorgestrel permeation rate through human skin

OBJECTIVE:To investigate effects of ethylene/vinyl acetate copolymer(EVAc) membrane with various weight fraction rate of vinyl acetate,different membrane thickness and different skin permeation enhancers on levonorgestrel permeation rate through human skin.METHODS:The Valia-Chien permeation cells and HPLC were used to determine the permeation of LNG in 70% ethanol saturated solution under the above different conditions.RESULTS:The permeation rate of LNG through EVAc membrane-covered human skin showed a zero-order permeation kinetics,with rate increased as increasing the weight fraction of vinyl acetate in the copolymer(280 g·kg^-1>180 g·kg^-1>140 g·kg^-1),but decreased as increasing the thickness of membrane.The permeation rate was proportional to the reciprocal of the membrane thickness(r=0.992 9).Enhancers(20 g·kg ^-1oleicacid and 20 g·kg^-1 azone) can further increase the permeation of LNG.CONCLUSION:The skin permeation rate of LNG can meet the requirement with 20 g·kg^-1 OA and proper EVAc member(50 μm,280 g·kg^-1 Vac).