Yamaguchi Y, Usami T, Natsume H, Aoyagi T, Nagase Y, Sugibayashi K, Morimoto Y
Faculty of pharmaceutical Sciences, Josai University, Saitama, Japan.
Chem Pharm Bull (Tokyo). 1997 Mar;45(3):537-41. doi: 10.1248/cpb.45.537.
Four polymeric membranes were prepared consisting of various ratios of 2-hydroxyethyl-methacrylate/polydimethylsiloxane-methacrylate copolymer. These membranes had both lipophilic and hydrophilic domains in their copolymer networks like skin barrier. From permeation studies of the aqueous solutions or suspensions of various lipophilic and hydrophilic drugs using these membranes, a membrane having a similar drug permeability to hairless rat and human skins was selected. Permeation of indomethacin through the selected polymer membrane from simple ointment, gel and a marketed cream were then measured. About 10(2) times higher permeability was found in the polymer membrane than through excised hairless rat skin, but the rank order of the permeability through the polymer membrane among the formulations was the same through the skin membranes. These higher permeations of indomethacin were probably related to physical and chemical properties of pharmaceutical additives in the topical formulations. It is concluded that these synthetic polymer membranes may be utilized as an alternative tool to predict human or rat skin permeability of various (hydrophilic or lipophilic) drugs as well as to screen drug candidates for transdermal drug delivery.
制备了四种由不同比例的甲基丙烯酸2-羟乙酯/聚二甲基硅氧烷甲基丙烯酸酯共聚物组成的聚合物膜。这些膜在其共聚物网络中具有亲脂性和亲水性区域，类似于皮肤屏障。通过使用这些膜对各种亲脂性和亲水性药物的水溶液或悬浮液进行渗透研究，选择了一种对无毛大鼠和人皮肤具有相似药物渗透性的膜。然后测量了吲哚美辛从简单软膏、凝胶和市售乳膏通过所选聚合物膜的渗透率。发现聚合物膜中的渗透率比通过切除的无毛大鼠皮肤高约10²倍，但在不同制剂中通过聚合物膜的渗透率排序与通过皮肤膜的排序相同。吲哚美辛的这些较高渗透率可能与局部制剂中药物添加剂的物理和化学性质有关。得出的结论是，这些合成聚合物膜可作为一种替代工具，用于预测各种（亲水性或亲脂性）药物在人或大鼠皮肤中的渗透性，以及筛选透皮给药的候选药物。
