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  • Diffusion modeling of percutaneous absorption kinetics: 3. Variable diffusion and partition coefficients, consequences for stratum corneum depth profiles and desorption kinetics

    Author(s)
    Anissimov, YG
    Roberts, MS
    Griffith University Author(s)
    Anissimov, Yuri G.
    Year published
    2004
    Metadata
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    Abstract
    Stratum corneum (SC) desorption experiments have yielded higher calculated steady-state fluxes than those obtained by epidermal penetration studies. A possible explanation of this result is a variable diffusion or partition coefficient across the SC. We therefore developed the diffusion model for percutaneous penetration and desorption to study the effects of either a variable diffusion coefficient or variable partition coefficient in the SC over the diffusion path length. Steady-state flux, lag time, and mean desorption time were obtained from Laplace domain solutions. Numerical inversion of the Laplace domain solutions was ...
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    Stratum corneum (SC) desorption experiments have yielded higher calculated steady-state fluxes than those obtained by epidermal penetration studies. A possible explanation of this result is a variable diffusion or partition coefficient across the SC. We therefore developed the diffusion model for percutaneous penetration and desorption to study the effects of either a variable diffusion coefficient or variable partition coefficient in the SC over the diffusion path length. Steady-state flux, lag time, and mean desorption time were obtained from Laplace domain solutions. Numerical inversion of the Laplace domain solutions was used for simulations of solute concentration-distance and amount penetrated (desorbed)-time profiles. Diffusion and partition coefficients heterogeneity were examined using six different models. The effect of heterogeneity on predicted flux from desorption studies was compared with that obtained in permeation studies. Partition coefficient heterogeneity had a more profound effect on predicted fluxes than diffusion coefficient heterogeneity. Concentration-distance profiles show even larger dependence on heterogeneity, which is consistent with experimental tape-stripping data reported for clobetasol propionate and other solutes. The clobetasol propionate tape-stripping data were most consistent with the partition coefficient decreasing exponentially for half the SC and then becoming a constant for the remaining SC.
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    Journal Title
    Journal of Pharmaceutical Sciences
    Volume
    93
    Issue
    2
    Publisher URI
    http://www.aapspharmaceutica.com/publications/journal.asp?Journal=j.%20pharm.%20sci.
    DOI
    https://doi.org/10.1002/jps.10567
    Copyright Statement
    © 2004 John Wiley & Sons, Ltd. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the author for more information.
    Subject
    Pharmacology and pharmaceutical sciences
    Publication URI
    http://hdl.handle.net/10072/16921
    Collection
    • Journal articles

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