6533b86cfe1ef96bd12c892c

RESEARCH PRODUCT

A modelistic approach showing the importance of the stagnant aqueous layers in in vitro diffusion studies, and in vitro-in vivo correlations

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Abstract The present study deals with the role of the aqueous diffusion layers on the in vitro penetration of xenobiotics across artificial lipoidal membranes, and their ability to reproduce biophysical absorption models when in vivo results are to be simulated from the in vitro tests. The aqueous boundary layers which are invariably formed on artificial lipoidal membranes can be optionally preserved or disrupted, according to the type of absorption site which should be simulated, a condition which could reasonably lead to a better correspondence between in vitro and in vivo results; in practice, disruption of water layers can be easily achieved by a synthetic surfactant solution at its critical micelle concentration, in contact with the desired membrane side. This approach is illustrated by using a dimethylpolysiloxane artificial membrane, 4-alkylanilines as permeant test compounds, and the nonionic polysorbate 80 as model surfactant, in a series of experiments developed with a Franz-type diffusion cell apparatus. Experimental designs simulating different types of biological absorbing membranes, merely by changing the number of aqueous boundary layers, are described and analyzed. Apart from the effects of the water layers, it is shown that perfect sink conditions at the receptor side must be strictly maintained in order to obtain reliable results.