Determination of Solute Diffusion Properties in Artificial Sebum

J Pharm Sci. 2019 Sep;108(9):3003-3010. doi: 10.1016/j.xphs.2019.04.027. Epub 2019 May 2.

Abstract

Despite a number of studies showed that hair follicular pathway contributed significantly to transdermal delivery, there have been limited studies on the diffusion properties of chemicals in sebum. Here, the diffusion property of 17 chemical compounds across artificial sebum has been measured using diffusion cell. The diffusion flux showed 2 types of distinctive behaviors: that reached steady state and that did not. Mathematical models have been developed to fit the experimental data and derive the sebum diffusion and partition coefficients. The models considered the uneven thickness of the sebum film and the additional resistance of the unstirred aqueous boundary layer and the supporting filter. The derived sebum-water partition coefficients agreed well with the experimental data measured previously using equilibrium depletion method. The obtained diffusion coefficients in artificial sebum only depended on the molecular size. Change in pH for ionic chemicals did not affect the diffusion coefficients but influenced their diffusion flux because of the change of sebum-water partition coefficients. Generally, the measured diffusion coefficients of chemicals in artificial sebum are about one order of magnitude higher than those in the stratum corneum lipids, suggesting the hair follicle might have a non-negligible contribution to the overall permeation.

Keywords: Mathematical model; diffusion; lipids; pH; transdermal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / metabolism*
  • Diffusion
  • Hydrogen-Ion Concentration
  • Permeability
  • Sebum / chemistry
  • Sebum / metabolism*
  • Skin Absorption
  • Solutions / pharmacokinetics*
  • Water / chemistry

Substances

  • Solutions
  • Water