Dependence of Skin Permeability on Contact Area

Abstract

Purpose. We report that experimentally measured skin permeability to hydrophilic solutes increases with decreasing contact area between the formulation and the skin. Our results suggest that an array of smaller reservoirs should thus be more effective in increasing transdermal drug delivery compared to a large single reservoir of the same total area.

Methods. Experimental assessment of the dependence of skin permeability on reservoir size was performed using two model systems, an array of liquid reservoirs with diameters in the range of 2 mm to 6 mm and an array of gel disk reservoirs with diameters in the range of 3 mm to 16 mm. Full thickness pig skin was used as an experimental model. Two molecules, sodium lauryl sulfate (SLS) and oleic acid, were used as model penetration enhancers.

Results. Mannitol transport per unit area into and across the skin increased with a decrease in the contact area between the skin and the formulation. Mannitol permeability increased approximately 6-fold with a decrease in the reservoir size from 16 mm to 3 mm in presence of 0.5% SLS in PBS (phosphate buffered saline) as a permeability enhancer. Similar results were obtained when oleic acid was used as an enhancer.

Conclusions. To explain the observed dependence of transdermal transport on contact area a simple mathematical model based on skin geometry in the reservoir was developed. The model predicts a lateral strain in the skin due to preferential swelling of skin upon penetration of water. We propose that this lateral strain is responsible for the increased skin permeability at lower reservoir sizes.