Distributed diffusion-clearance model for transient drug distribution within the skin

Journal of Pharmaceutical Sciences
Kosmas KretsosJohannes M Nitsche

Abstract

Quantitative predictions of molecular transport rates through the skin are key to the development of topically applied and transdermally delivered drugs, as well as risk assessment associated with dermal exposure. Most research to date has focused on correlations for the permeability of the stratum corneum, and transient diffusion models that oversimplify vascular clearance processes in terms of a perfect-removal boundary condition at an artificially introduced lower boundary. Considerations of the spatially distributed nature and action of blood vessels have usually been limited to the steady-state case. This article describes a more comprehensive transient model of percutaneous absorption formulated in terms of volumetric dispersion and clearance coefficients reflecting the spatial distribution of vascular processes. The model was implemented through an analysis of published experimental results on in vivo permeation of salicylic acid (SA) in de-epidermized rat skin. With regard to the characterization of SA in rat dermis ("de") in vivo, it was found that: (i) SA is likely to have a dermal effective partition coefficient (relative to pH 7.4 aqueous buffer "pH7.4") around unity (K(de/pH7.4) = 0.9 +/- 0.3); (ii) vascular proces...Continue Reading

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Citations

Apr 28, 2011·Pharmaceutical Research·Yuri G Anissimov, Michael Stephen Roberts
Jan 21, 2012·Advanced Drug Delivery Reviews·H Frederick Frasch, Ana M Barbero
May 12, 2012·Advanced Drug Delivery Reviews·Yuri G AnissimovMichael S Roberts
Jul 4, 2012·Advanced Drug Delivery Reviews·Dominik SelzerDirk Neumann
Apr 25, 2012·Advanced Drug Delivery Reviews·Owen G JeppsMichael S Roberts
May 26, 2012·Advanced Drug Delivery Reviews·Steffi HansenUlrich F Schaefer
Nov 13, 2012·Advanced Drug Delivery Reviews·Arne NaegelGabriel Wittum
Feb 5, 2014·Expert Opinion on Drug Metabolism & Toxicology·Yuri G Anissimov
Dec 7, 2007·Cutaneous and Ocular Toxicology·David Basketter, Gavin Maxwell
Dec 29, 2005·Journal of Pharmaceutical Sciences·Gerald B Kasting, Matthew A Miller
Apr 22, 2015·Journal of Pharmaceutical Sciences·Matthew A Miller, Gerald B Kasting
Jun 10, 2010·Journal of Pharmaceutical Sciences·Rania Ibrahim, Gerald B Kasting
Mar 2, 2011·International Journal of Pharmaceutics·Samir MitragotriMichael S Roberts
Jun 6, 2008·International Journal of Pharmaceutics·G CevcS Mazgareanu
Oct 12, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Hemali B Gunt, Gerald B Kasting
Feb 17, 2007·Mathematical Biosciences·Kosmas Kretsos, Gerald B Kasting
Jan 27, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gregor Cevc, Ulrich Vierl
Aug 19, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jason T Chittenden, Jim E Riviere
Jun 2, 2009·Journal of Applied Toxicology : JAT·David A Basketter, Ian Kimber
Apr 1, 2012·Journal of Inclusion Phenomena and Macrocyclic Chemistry·Haitao YangLisa C Rohan
Oct 6, 2020·Expert Opinion on Drug Metabolism & Toxicology·Joshua J CalcuttYuri G Anissimov
Mar 26, 2021·Journal of Pharmaceutical Sciences·Joshua J Calcutt, Yuri G Anissimov

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