COMPARISON OF PERMEABILITY DATA FROM TRADITIONAL DIFFUSION CELLS AND ATR-FTIR SPECTROSCOPY .2. DETERMINATION OF DIFFUSIONAL PATHLENGTHS IN SYNTHETIC MEMBRANES AND HUMAN STRATUM-CORNEUM

In this study, the morphological structure of the inner and outer regi ons of human stratum corneum (SC) were investigated using Attenuated T otal Reflectance Fourier Transform Infra-Red (ATR-FTIR) spectroscopy. Furthermore, diffusional pathlengths in silicone membranes and human S C were determined using ATR-FTIR spectroscopic data and regular skin d iffusion cell data. SC membranes were fully hydrated throughout the ex periments. It was shown that diffusion coefficients for a model permea nt, 4-cyanophenol (CP), were lower in the more compact regions of the inner layers of the SC when compared to diffusion coefficients in the outer layers. Partition coefficients between SC and aqueous vehicles w ere higher in the outer layers than the inner layers. These data demon strate a 4-fold lower permeability of skin to CP in the inner layers r elative to the outer layers of the SC. The combination of diffusion ce ll data and ATR-FTIR spectroscopic data was also used to determine dif fusional pathlengths across synthetic silicone membranes and human SC. In all cases, the pathlengths were similar to the thickness of the me mbranes. For SC, this appears to contrast the commonly held theory tha t diffusion occurs via a tortuous route within the intercellular lipid s, and may therefore imply a transcellular route. Alternatively, the c alculated pathlengths may be a reflection of the total length of rate limiting steps in the diffusional process rather than overall diffusio nal distance. This implies that lateral molecular diffusion within the head groups or lipid tails (depending on the lipophilicity of the per meant) of the lipid bilayers may be a relatively rapid process. These results have demonstrated that the previously observed morphological d ifferences between the inner and outer regions of the SC are reflected in variations in permeability, and that the diffusional route through fully hydrated human SC may indeed be via a direct pathway. (C) 1997 Elsevier Science B.V.