Membrane Diffusion: Consequences for Transdermal Drug Delivery
by
Owen Jepps
Griffith University
Coauthors: M. S. Roberts

Knowledge of the rate of solute permeation through the skin is important in applications such as therapeutic drug delivery and toxicological assessment. Standardized experimental techniques are used to measure this rate, which generally reaches a quasi-steady state after an initial lag. As skin permeation of solutes is generally taken to be diffusive, a fairly straightforward model of diffusion through a membrane is used to extract a permeation rate from such data. The model theory predicts a linear dependence of this rate on the diffusion coefficient and the skin-solvent partitioning (lipophilicity).

Such a monotonic relationship sits at odds with other experimental data demonstrating a symmetric, somewhat parabolic variation of permeability with lipophilicity, about an optimal lipophilicity for peak penetration. These results have inspired various ad hoc models, designed to account for this behaviour.

We have taken a first-principles, thermodynamically motivated approach to model the role of lipophilicity in skin permeation. In doing so, we uncover possible reasons behind the failure of the traditional skin permeation model to capture this symmetry, which is largely related to the assumed boundary conditions. We also investigate the implications of our model for other skin permeation phenomena, including the so-called reservoir effect.

Date received: January 10, 2010