Diffusion modeling of percutaneous absorption kinetics. 1. Effects of flow rate, receptor sampling rate, and viable epidermal resistance for a constant donor concentration

A diffusion model for the percutaneous absorption of a solute through the skin is developed for the specific case of a constant donor concentration with a finite removal rate from the receptor due to either perfusion rate or sampling. The model has been developed to include a viable epidermal resistance and a donor-stratum corneum interfacial resistance. Numerical inversion of the laplace domain solutions were used for simulations of solute flux and cumulative amount absorbed and to model specific examples of percutaneous absorption. Limits of the Laplace domain solutions were used to define the steady-state flux, lag time, and receptor concentration. Steady-state approximations obtained from the solutions were used to relate the steady-state flux and the effective permeability coefficient to the viable epidermis resistance, a donor-stratum corneum interfacial resistance, receptor removal rate, and partitioning between the receptor and donor phases. The lag time was shown to be dependent on these parameters and on the Volume of the receptor phase. It is concluded that curvilinear cumulative amount and flux-time profiles are dependent on the processes affecting percutaneous absorption, the shapes of the profiles reflecting the processes most determining transport.