EVAc膜及促进剂对左炔诺孕酮人皮肤渗透速率的影响

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

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，ｒ＝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。

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 -1 oleicacid 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).