Quantitative structure permeability relationships for phenolic compounds applied to human epidermal membranes in...

This study examined how solvent-skin-solute interactions influenced the human epidermal permeation of three similar-sized phenolic compounds applied in a series of different solvents.

Human epidermal permeation fluxes and lag times of three phenolic compounds were assessed in Franz cells for a range of solvents varying in molecular size and solubility parameters. In order to develop a mechanistic understanding of the determinants of the permeation findings, the solubility of the compounds in solvents and stratum corneum, the extent of solvent uptake by the stratum corneum and the impact of the solvents on skin hydration and transepidermal water loss were also measured.

Maximum epidermal fluxes and lag times varied greatly with the various solvent used. Markedly enhanced epidermal permeability fluxes, prolonged lag times and reduced diffusivities of the compounds were evident for many of the solvents. A solvent induced increase in stratum corneum solubility was associated with the uptake of solvent containing dissolved compound into the stratum corneum intercellular lipids, corneodesmosomes, lacunae and corneocytes. This uptake was dependent on both the solvent molecular size and the solubility of the compounds in the solvents. The imbibed solvent led to variable compound uptake, increased thermodynamic activity and modulated flux with, in some cases, reduced diffusion and a prolonged lag time.

The solubility, permeation and lag times of compounds in the stratum corneum can be modulated by solvent uptake. Whilst a solvent-induced stratum corneum reservoir effect for a compound may prolong its lag time for a compound before steady state permeation is reached, it does not affect its overall steady state transport defined by variations in SC solubility and diffusion of its free form after solvent exposure.