托特罗定压敏胶分散型贴剂在大鼠体外/内的透过性评价  

In vitro/in vivo Evaluation of Drug-in-adhesive Patches of Tolterodine in Rats

作　　者：赵利刚[1] 李燕[2] 方亮[3] 吕立勋[1] 赵琳琳[1] 

机构地区：[1]河北联合大学药学院,河北唐山063000 [2]唐山市妇幼保健院药剂科,河北唐山063000 [3]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《中国医药工业杂志》2013年第6期585-588,共4页Chinese Journal of Pharmaceuticals

摘　　要：分别以丙烯酸树脂压敏胶和硅酮压敏胶为基质制备托特罗定压敏胶分散型贴剂,结果采用硅酮压敏胶的制品中药物稳态渗透速率较高。又制备了以硅酮压敏胶为基质、含不同促透剂[月桂氮酮、N-甲基吡咯烷酮(NMP)、薄荷醇、油酸薄荷醇酯(M-OA)或庚酸薄荷醇酯(M-HEP)]的制品,结果促渗透作用由大到小依序为:M-OA>NMP>M-HEP,月桂氮酮及薄荷醇对托特罗定均无明显促透作用。大鼠药动学研究结果表明,空白组及加入M-OA的贴剂组大鼠稳态血药浓度(css)分别为0.69和0.97 g/ml;计算得相应的稳态血药浓度预测值(cssP)分别为0.60和0.93 g/ml,表明该制品具有良好的体内外相关性。The drug-in-adhesive patches loaded with tolterodine were prepared with acrylic or silicone pressure sensitive adhesive. The results showed that the product with silicone pressure sensitive adhesive had a faster in vitro steady state permeation rate. The different penetration enhancers EAzone, N-methylpyrrolidone （NMP）, menthol, （E）- 2-isopropyl-5-methylcyclohexyl octadec-9-enoate （M-OA） or 2-isopropyl-5-methylcyclohexyl heptanoate （M-HEP）] were added into the optimal product to investigate the enhancing effect. The results showed that the effects of different enhancers on tolterodine were in the following order of M-OA〉NMP〉M-HEP, but menthol and Azone had no significant effect on tolterodine. The mean steady-state plasma concentrations in rats after applying patches without enhancer or with M-OA as enhancer were 0.69 and 0.97 μg/ml, respectively. The in vivo results observed from these two types of patches in rats were in good agreement with the plasma concentrations predicted from the in vitro data, which were 0.60 and 0.93μg/ml. It indicated that there was a good relationship between the in vitro and in vitro experiments.

关 键 词：托特罗定 薄荷醇酯衍生物 压敏胶分散型贴剂 体外透皮 药动学 

分 类 号：R944.9[医药卫生—药剂学]