Permeation kinetics of active drugs through lanolin-based artificial membranes

Abstract

Skin-penetration studies play an essential role in the selection of drugs for dermal or transdermal application. In vivo experiments in humans are not always possible for ethical, practical, or economic reasons, especially in the first part of the drug development. It is necessary to develop alternative methods using accessible and reproducible surrogates for in vivo human skin. The in vitro methodologies using biological membranes (human and animal skin) are recognized and well accepted as an alternative but present high inter- and intra-individual variability. Therefore, the formation of synthetic membranes has been studied to obtain skin- mimicking models for permeation studies. The aim of this work is to create lanolin-based artificial membranes that can mimic the absorption through the skin of compounds applied topically.

A series of synthetic membranes using two different types of lanolin (water-extracted (WE) and solvent-extracted (SE)) were prepared. Next, the in vitro release test of three drugs (diclofenac sodium, ibuprofen and lidocaine) was performed on artificial membranes and on porcine skin placed on Franz cells. The percentage of release, flux, permeability coefficient, lag time, area under the curve, maximal concentration and time were determined for each compound in the different types of membrane.

The results showed that lanolin membranes presented a strong diminution of permeability compared to most artificial membranes, leading to a very similar permeability to that of skin. The SE and WE membranes showed a diminution of transepidermal water loss and permeability of compounds compared with membranes alone. The results from WE membranes were similar to those found for the skin. The lanolin membranes were not capable of perfectly mimicking permeation through the skin, but they did have the same rank order of drug penetration as the skin. It may be deduced from these tests that these systems provide more reliable results for compounds with low to medium lipophilicity. The results demonstrated that new lanolin-based artificial membranes have the potential to be exploited as screening models for determining the permeability of a compound destined to be topically delivered.