Permeation mechanisms through artificial lipoidal membranes and effects of synthetic surfactants on xenobiotic permeability.
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.
Pérez-Buendía
M D
MD
Department of Pharmacology and Pharmaceutics, University of Valencia, Spain.
Gómez-Pérez
B
B
Plá-Delfina
J M
JM
D000042:Absorption; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D008055:Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D008823:Micelles; D010539:Permeability; D011136:Polysorbates; D012833:Siloxanes; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D015262:Xenobiotics / Q000737:chemistry*
D008055:Lipids; D008567:Membranes, Artificial; D008823:Micelles; D011136:Polysorbates; D012833:Siloxanes; D013501:Surface-Active Agents; D015262:Xenobiotics