A theoretical analysis of permeation of small hydrophobic solutes across the stratum corneum based on Scaled Particle Theory

Abstract

The barrier properties of skin originate from its lipid bilayers whose ordered structure retards solute transport. The objective of this study is to develop a mathematical model that can predict skin permeability to small (MW < 500 Da), hydrophobic solutes based on the fundamental transport properties of skin lipid bilayers. We developed a mathematical model to predict two major transport properties (i.e., partition and diffusion coefficients) using important structural properties of lipid bilayers and molecular properties of the solute. The predictions are based on Scaled Particle Theory that calculates these properties using statistical mechanics of lipid chains. The calculations predict that solute partition coefficients in lipid bilayers are of the same order as those measured in isotropic solvents, such as octanol (Ko/w). On the other hand, solute diffusion coefficients decrease exponentially with solute cross‐sectional area. The resulting equation to predict skin permeability is given by(A1)P=5.6×10−6Ko/w0.7exp(−0.46r2)where r is solute molecular radius in Angstroms (Å) and P is in cm/s. The predicted skin permeabilities compare well with the experimental data. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:744–752, 2002