Pérez-Buendía M D, Gómez-Pérez B, Plá-Delfina J M
Department of Pharmacology and Pharmaceutics, University of Valencia, Spain.
Arzneimittelforschung. 1993 Jul;43(7):789-94.
Through the use of permeation/lipophilicity correlations, the mechanisms of permeation of selected test compounds across artificial lipoidal membranes of the polysiloxane type, in the absence and in the presence of a nonionic surfactant (Polysorbate 80), are investigated, in order to design "in vitro" conditions and features suitable for reproducing "in vivo" intestinal absorption tests, as well as to validate some conclusions arising from "in situ" rat gut experiments about the effects of the synthetic surfactants on drug and xenobiotic absorption processes. Six 4-alkylanilines showing a perfect homology were used as test compounds. The reported results clearly show that the in situ biophysical absorption (diffusion) models are completely reproduced by in vitro tests, provided that perfect sink conditions are achieved. Further selection of artificial membrane polarity should be necessary, however, in order to exactly equalize in vitro and in situ permeation rates. As far as the synthetic surfactant action on permeability is concerned, our conclusions are similar to those drawn from in situ studies, except that the effect of the surfactant on membrane polarity is much smaller and the micelle-solubilizing effect somewhat larger. The disruption of the aqueous stagnant diffusion layers adjacent to the membranes by the surfactant has been conclusively demonstrated. A clear first-element deviation for aniline, which prevents its inclusion as a term of the tested series, has been observed; this feature should be borne in mind whenever any in vivo/in vitro correlation has to be established.
通过运用渗透/亲脂性相关性，研究了所选测试化合物在不存在和存在非离子表面活性剂（聚山梨酯80）的情况下，跨聚硅氧烷类型人工脂质膜的渗透机制，以便设计适合重现“体内”肠道吸收试验的“体外”条件和特征，并验证一些源自“原位”大鼠肠道实验的关于合成表面活性剂对药物和外源性物质吸收过程影响的结论。六种具有完美同系性的4-烷基苯胺被用作测试化合物。所报道的结果清楚地表明，只要实现完美的漏槽条件，体外试验就能完全重现原位生物物理吸收（扩散）模型。然而，为了使体外和原位渗透速率完全相等，有必要进一步选择人工膜的极性。就合成表面活性剂对渗透性的作用而言，我们的结论与原位研究得出的结论相似，只是表面活性剂对膜极性的影响要小得多，而胶束增溶作用要大一些。已确凿证明表面活性剂会破坏与膜相邻的水停滞扩散层。已观察到苯胺存在明显的首元素偏差，这使其无法作为测试系列的一项；每当必须建立任何体内/体外相关性时，都应牢记这一特征。
