Skin is a very effective barrier and as a result resists transdermal drug delivery. Permeation enhancers are used to improve drug delivery through the skin by altering the structure and dynamics of the skin.
Simulation can be used to study transdermal drug delivery. However, the standard linear diffusion equation does not apply in the case of permeation enhancers, resulting in the need for a new approach to determining the drug delivery rate when enhancers are used.
Figure 1. Cross-section of skin showing the two main layers: epidermis and dermis. Drugs must pass through the two sublayers of the epidermis to reach the micro circulation of the dermis (from Wikipedia)
Veryst captured the effect of the permeation enhancer by specifying that the drug diffusivity increases with concentration of the enhancer. We developed a finite element model of drug diffusion from an adhesive patch that accounts for that effect. We also took into account partitioning (concentration discontinuity) of the drug and enhancer at the interface of the patch and skin because solubilities of the species are different in the two materials. This model enables the accurate prediction of drug flux to the skin and its dependence on the properties of the permeation enhancer.
We compared our results with experimental data (Rim, J.E., Pinsky, P.M. & van Osdol, W.W., Annals of Biomedical Engineering, Vol. 33, 2005) reported for a case where the drug is fentanyl and the enhancer is lauryl pyroglutamate. Our model predicts the experimental maximum flux value and its increase with the enhancer concentration. Figure 2 shows the experimental and calculated fluxes without and with the enhancer. The initial enhancer concentration in the patch is 0 or 0.12 g/cm3.
For more information, see Designing Effective Transdermal Drug Delivery Patches with Simulation.