Mathematical models of skin permeability: an overview.
ABSTRACT Mathematical models of skin permeability play an important role in various fields including prediction of transdermal drug delivery and assessment of dermal exposure to industrial chemicals. Extensive research has been performed over the last several decades to yield predictions of skin permeability to various molecules. These efforts include the development of empirical approaches such as quantitative structure-permeability relationships and porous pathway theories as well as the establishment of rigorous structure-based models. In addition to establishing the necessary mathematical framework to describe these models, efforts have also been dedicated to determining the key parameters that are required to use these models. This article provides an overview of various modeling approaches with respect to their advantages, limitations and future prospects.
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ABSTRACT: A comprehensive transient model of chemical penetration through the stratum corneum, viable epidermis and dermis formulated in terms of an Excel™ spreadsheet and associated add-in is presented. The model is a one-dimensional homogenization of underlying microscopic transport models for stratum corneum and dermis; viable epidermis is treated as unperfused dermis. The model's salient features are a detailed structural description of the skin layers, a combination of first-principles based transport equations and empirical partition and diffusion coefficients, and the capability of simulating a variety of exposure scenarios. Model predictions are compared with representative in vitro skin permeation data obtained from the literature using as summary parameters total absorption (Q(abs)), maximum flux (J(max)) and skin permeability coefficient (k(p)). The results of this evaluation demonstrate the current state-of-the-art in prediction of transient skin absorption and highlight areas in which further elaborations are needed to obtain satisfactory predictions.Advanced drug delivery reviews 02/2013; 65(2):221-236. · 11.96 Impact Factor
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ABSTRACT: To use a diffusion model for predicting skin absorption requires accurate estimates of input parameters on model geometry, affinity and transport characteristics. This review summarizes methods to obtain input parameters for diffusion models of skin absorption focusing on partition and diffusion coefficients. These include experimental methods, extrapolation approaches, and correlations that relate partition and diffusion coefficients to tabulated physico-chemical solute properties. Exhaustive databases on lipid-water and corneocyte protein-water partition coefficients are presented and analyzed to provide improved approximations to estimate lipid-water and corneocyte protein-water partition coefficients. The most commonly used estimates of lipid and corneocyte diffusion coefficients are also reviewed. In order to improve modeling of skin absorption in the future diffusion models should include the vertical stratum corneum heterogeneity, slow equilibration processes, the absorption from complex non-aqueous formulations, and an improved representation of dermal absorption processes. This will require input parameters for which no suitable estimates are yet available.Advanced drug delivery reviews 05/2012; · 11.96 Impact Factor