Skin solubility determines maximum transepidermal flux for similar size molecules

Zhang, Qian, Grice, Jeffrey E., Li, Peng, Jepps, Owen G., Wang, Guang-Ji and Roberts, Michael S. (2009) Skin solubility determines maximum transepidermal flux for similar size molecules. Pharmaceutical Research, 26 8: 1974-1985. doi:10.1007/s11095-009-9912-4


Author Zhang, Qian
Grice, Jeffrey E.
Li, Peng
Jepps, Owen G.
Wang, Guang-Ji
Roberts, Michael S.
Title Skin solubility determines maximum transepidermal flux for similar size molecules
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
Publication date 2009-06-05
Year available 2009
Sub-type Article (original research)
DOI 10.1007/s11095-009-9912-4
Open Access Status DOI
Volume 26
Issue 8
Start page 1974
End page 1985
Total pages 12
Editor Vincent H.L. Lee
Place of publication United States
Publisher Springer New York
Language eng
Subject C1
030405 Molecular Medicine
9202 Health and Support Services
Abstract 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.
Formatted 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 (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
Keyword Maximum flux
Structure- penetration relationships
Transdermal permeation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 40 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 17:52:42 EST by Mr Andrew Martlew on behalf of Medicine - Princess Alexandra Hospital