A two-layer diffusive model for describing the variability of transdermal drug permeation

There is mounting evidence that the permeability coefficients (kp) that describe any given transdermal drug permeation process generally follow some form of positively skewed, non-symmetrical distribution rather than a simple normal distribution. Yet a suitable theoretical treatment of this area has not been undertaken to date. In this paper, we describe a two-layer model that can explain five drugs’ kp variabilities as measured in two previously published papers. The model shows why rapidly permeating drugs would tend to exhibit more symmetrical kp distributions while progressively more slowly permeating drugs would tend to exhibit progressively more positively skewed kp distributions. Future research should take this effect into account when comparing the flux variabilities of hydrophilic and lipophilic drugs.