Purpose <p>In membrane transport studies utilizing a diffusion cell such as In Vitro Permeation Test (IVPT), mass transport is not purely one-dimensional from the donor to the receptor. Lateral diffusion within the membrane into the surrounding clamped region leads to edge effect—an increase in flux caused by lateral transport. In conventional skin permeation studies when the membrane is relatively thin compared to the diameter of the diffusion cell opening, edge effect is insignificant under the assumption of isotropic diffusion. However, biological membranes such as skin are not homogenous and diffusion within the membrane can be anisotropic (e.g., lateral diffusion can occur faster than transverse diffusion across the membrane).</p> Methods <p>This study evaluated the edge effect under these conditions using COMSOL Multiphysics simulations.</p> Results <p>The results indicated that the edge effect was evident but small for steady-state fluxes across a membrane (~ 4% to 10% flux increase) when the lateral diffusion coefficients were 10 to 30 times larger than the transverse diffusion coefficients, and the edge effect increased with increasing lateral diffusion coefficient and decreasing diffusion cell opening size.</p> Conclusions <p>The findings suggested that edge effect should be considered when performing and interpreting IVPT data for membranes with either high anisotropy or small diffusion cell openings.</p>