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  • Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

    Author(s)
    Zhang, Qian
    Grice, Jeffrey E
    Li, Peng
    Jepps, Owen G
    Wang, Guang-Ji
    Roberts, Michael S
    Griffith University Author(s)
    Jepps, Owen
    Year published
    2009
    Metadata
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    Abstract
    Purpose The maximum flux of solutes penetrating the epidermis has been known to depend predominantly on solute molecular weight. Here we sought to establish the mechanistic dependence of maximum flux on other solute physicochemical parameters. Methods Maximum fluxes, stratum corneum solubilities and estimated diffusivities through human epidermis were therefore determined for 10 phenols with similar molecular weights and hydrogen bonding but varying in lipophilicity. Results Maximum flux and stratum corneum solubilities of the phenolic compounds both showed a bilinear dependence on octanol-water partition coefficient ...
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    Purpose The maximum flux of solutes penetrating the epidermis has been known to depend predominantly on solute molecular weight. Here we sought to establish the mechanistic dependence of maximum flux on other solute physicochemical parameters. Methods Maximum fluxes, stratum corneum solubilities and estimated diffusivities through human epidermis were therefore determined for 10 phenols with similar molecular weights and hydrogen bonding but varying in lipophilicity. Results Maximum flux and stratum corneum solubilities of the phenolic compounds both showed a bilinear dependence on octanol-water partition coefficient (P), with solutes having a maximum solubility in the stratum corneum when 2.7<log P<3.1. In contrast, lag times and diffusivities were relatively independent of P. Stratum corneum-water partition coefficients and epidermal permeability coefficients were consistent with previously reported data. Conclusion A key finding is that the convex dependence of maximum flux on lipophilicity arises primarily from variations in stratum corneum solubility, and not from diffusional or partitioning barrier effects at the stratum corneum-viable epidermis interface for the more lipophilic phenols. Our data support a solute structure-skin transport model for aqueous solutions in which permeation rates depend on both partitioning and diffusivity: partitioning is related to P, and diffusivity to solute size and hydrogen bonding.
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    Journal Title
    Pharmaceutical Research
    Volume
    26
    Issue
    8
    DOI
    https://doi.org/10.1007/s11095-009-9912-4
    Subject
    Pharmaceutical Sciences
    Pharmacology and Pharmaceutical Sciences
    Publication URI
    http://hdl.handle.net/10072/30281
    Collection
    • Journal articles

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