Comparison of permeability data from traditional diffusion cells and ATR-FTIR spectroscopy. Part II. Determination of diffusional pathlengths in synthetic membranes and human stratum corneum

• Published in: International journal of pharmaceutics 1997-08, Vol.154 (2), p.217-227
• Main Authors: Pellett, Mark A., Watkinson, Adam C., Hadgraft, Jonathan, Brain, Keith R.
• Format: Article
• Language: English
• Subjects: Attenuated total reflectance; Biological and medical sciences; Diffusional pathlength; Fourier transform infrared spectroscopy; General pharmacology; Human stratum corneum; Medical sciences; Morphology; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Silicone membranes; Skin, nail, hair, dermoskeleton
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(97)00143-9

In this study, the morphological structure of the inner and outer regions of human stratum corneum (SC) were investigated using Attenuated Total Reflectance Fourier Transform Infra-Red (ATR-FTIR) spectroscopy. Furthermore, diffusional pathlengths in silicone membranes and human SC were determined using ATR-FTIR spectroscopic data and regular skin diffusion cell data. SC membranes were fully hydrated throughout the experiments. It was shown that diffusion coefficients for a model permeant, 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 were higher in the outer layers than the inner layers. These data demonstrate a 4-fold lower permeability of skin to CP in the inner layers relative to the outer layers of the SC. The combination of diffusion cell data and ATR-FTIR spectroscopic data was also used to determine diffusional pathlengths across synthetic silicone membranes and human SC. In all cases, the pathlengths were similar to the thickness of the membranes. For SC, this appears to contrast the commonly held theory that diffusion occurs via a tortuous route within the intercellular lipids, and may therefore imply a transcellular route. Alternatively, the calculated pathlengths may be a reflection of the total length of rate limiting steps in the diffusional process rather than overall diffusional distance. This implies that lateral molecular diffusion within the head groups or lipid tails (depending on the lipophilicity of the permeant) of the lipid bilayers may be a relatively rapid process. These results have demonstrated that the previously observed morphological differences 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.