A heterogeneous synthetic membrane to model the transdermal permeation of drugs

Transdermal drug delivery has been investigated with great interest over the years. Membranes used for such studies have included non-living animal skins. These preparations often have questionable reproducibility and may require tedious preparation procedures. Most of the reported work with synthetic skin models has assumed that a homogeneous hydrophobic phase serves as an adequate model. A limitation of such models is that they do not explain the passage of small highly polar permeants, which has been shown to occur in skin. The importance of both the lipid and protein regions in the transdermal absorption of drugs has been noted. This study uses a reproducible membrane of cross-linked gelatin with hydrophobic (oil) and aqueous phases incorporated in it. Unlike other synthetic skin models described in the literature, this one incorporates all three major components of the stratum corneum. The oil represents the lipid phase of the skin and imparts the partitioning effect. Water definitely plays a role in all permeation processes. The cross-linked gelatin (protein), represents the cellular keratin of the skin. It was found that isopropyl myristate incorporated into the membrane best models the hydrophobicity of skin for the permeation of the various substances tested. The permeation pathway taken by a drug through the film was found to depend on its size and physicochemical properties. An increase in hydrophobicity of the permeant was found to increase its permeability coefficient while increase in molecular weight or size of the drug had a negative effect The permeation barrier of the film occurs by a partition mechanism within a certain range of hydrophobicity of permeants and by a pore mechanism for more polar permeants. A permeant passing through the film was modeled to take one of two routes; a hydrophobic/hydrophilic dual pathway and a continuous hydrophilic path way.