Tsutsumi K, Obata Y, Takayama K, Loftsson T, Nagai T
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Drug Dev Ind Pharm. 1998 Aug;24(8):757-62. doi: 10.3109/03639049809082723.
Ergotamine tartrate (ET) is used clinically in the treatment of migraines. However, the bioavailability of ET is rather poor following oral administration. Therefore, we tried to improve ET delivery using buccal administration. The purpose of this study was to investigate the characteristics of the permeation of ET through the hamster cheek pouch in vitro using a two-chamber diffusion cell, and to evaluate the effect of permeation enhancers on the transbuccal delivery of ET. Cod-liver oil extract (CLOE), polyoxyethylene hydrogenated castor oil (HCO 60), sodium glycocholate (GC), and sodium caprate (CA) were selected as premeation enhancers considering their low irritancy of the mucosa. When the enhancers were added to the donor cell at a 5% concentration each, the ET permeation rate markedly increased compared with that in a control not containing enhancer. Among these enhancers, CLOE exhibited the greatest effect. Because CLOE is composed of 16 kinds of fatty acids, the enhancement action of each of the major components was separately determined. As major fatty acids, palmitic acid, oleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were selected and their enhancing effects were studied. The enhancing effect of each fatty acid was significantly lower than that of CLOE.
酒石酸麦角胺（ET）临床上用于治疗偏头痛。然而，口服给药后ET的生物利用度相当低。因此，我们尝试通过颊部给药来改善ET的递送。本研究的目的是使用双室扩散池体外研究ET透过仓鼠颊囊的渗透特性，并评估渗透促进剂对ET经颊递送的影响。考虑到它们对粘膜的低刺激性，选择了鱼肝油提取物（CLOE）、聚氧乙烯氢化蓖麻油（HCO 60）、甘氨胆酸钠（GC）和癸酸钠（CA）作为渗透促进剂。当将这些促进剂以5%的浓度分别添加到供体池中时，与不含促进剂的对照组相比，ET的渗透速率显著增加。在这些促进剂中，CLOE表现出最大的效果。由于CLOE由16种脂肪酸组成，分别测定了每种主要成分的增强作用。选择棕榈酸、油酸、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）作为主要脂肪酸，并研究了它们的增强作用。每种脂肪酸的增强作用均显著低于CLOE。
