Skin permeation

Obtaining experimental permeability data through human skin is a slow and expensive process. By using ERCO Pharma’s skin model we can obtain predicted permeation rates of multiple solutes across the stratum corneum, in silico, from which we then select the most promising candidates to continue with in the lab.

Correlation between experimentally obtained permeability-values and those predicted by ERCO Pharma’s skin model.

Our computational approach enables an unmatched flexibility when investigating the effects of various modifications to the system parameters. By performing free energy calculations in the lipid matrix of the stratum corneum, as well as in the vehicle, we can predict the partitioning of the active compound into the human skin barrier. Using molecular dynamics simulations we can then obtain the total permeation rate of the compound across the stratum corneum.

The general procedure for calculating the permeability of a compound through the stratum corneum intercellular lipid matrix. The potential of mean force (PMF) and local diffusion coefficient are obtained from forward-reverse nonequilibrium pulling through the system. The PMF is calibrated by calculating the binding free energy of the ligand, at the position where the PMF starts. (From Lundborg et al. Predicting drug permeability through skin using molecular dynamics simulation. J. Control. Release, 283 (2018))