Robert J. Scheuplein

TKANSPORT INTO AND WITHIN THE SKIN

SUMMARY.— Developments in recent years permit us to state the following principles which relate to percutaneous absorption. (1) The entire stratum corneum junctions as the rate‐limiting barrier in the skin. (2) For penetration from weak solutions, flux is directly proportional to the concentration of the penetrant in the solution which is presented to the cutaneous surface. (3) Flux increases as the solubility of the penetrant in the stratum corneum increases. (4) Flux increases as the mobility of the penetrant in the stratum corneum (diffusion constant) increases. (5) Flux decreases as the thickness of the membrane increases. (6) When concentrations in the presenting solution reach high values, flux is not proportional to concentration. (7) Flux through dermal tissue is much more rapid than flux through the stratum corneum.

On the application of rate theory to complex multibarrier flow co-ordinates: Membrane permeability

Abstract Zwolinski, Eyring & Reese (1949) , considering a cellular membrane as a succession of equal energy barriers, used absolute rate theory to derive a general expression for the steady-state flux. This theory is further generalized and adapted to complex flow co-ordinates more typical of actual solution membrane systems. The reciprocal of the permeability constant for very general flow co-ordinates is simply and intuitively expressed as a sum of linear terms, each term proportional to the product of a unique rate constant and an equilibrium constant. These are related to distribution and diffusion constants in the usual way and the influence of the various components of inhomogeneous membranes on the steady-state permeability (at zero volume flow) may be easily estimated. Applied to the simple lipid membrane the standard expression for the permeability constant is reclaimed. A similar treatment of the protein-lipid bilayer results in a clear illustration of the relative importance of various sublayers on permeability as a function of the water: lipid distribution ratio. The linear form of the equations makes them adaptable to the approximate solution of more general diffusion problems. A semi-imperical calculation of the average self diffusion constant for water within a pore in which the activation energy is a function of pore radius is described.