The penetration of drugs and other micromolecules through intact human skin can be regarded as a process of dissolution and molecular diffusion through a composite, multilayer membrane, whose principal barrier to transport is localized within the stratum corneum. A mathematical model of the stratum corneum as a two-phase protein-lipid heterogeneous membrane (in which the lipid phase is continuous) correlates the permeability of the membrane to a specific penetrant with the water solubility of the penetrant and with its lipid-protein partition coefficient.

Experimentally measured permeabilities of human skin to a variety of drugs have been found to conform to this model. The extraordinarily low permeability of skin to most micromolecules appears to arise from the very low diffusivity of such molecules in the intercellular lipid phase.