Evidence that drug flux across synthetic membranes is described by normally distributed permeability coefficients

Y. Frum, G.M. Eccleston, V.M. Meidan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Over recent decades, the use of in vitro diffusion cell studies to assess skin permeability has evolved into a major research tool, providing key insights into the relationships between skin, drug and formulation. Sometimes, such studies involve synthetic membranes as this approach can yield useful inferences with respect to drug-skin partitioning and diffusion phenomena. Yet despite the popularity of such studies, it is still not at all known whether typical solute transport across synthetic barriers results in a normal distribution of permeability coefficients or alternatively some type of skewed distribution. The present study aims to shed light on this issue. To this end, five compounds (testosterone, oestradiol, corticosterone, aldosterone and adenosine) exhibiting a broad range of octanol-water partition coefficient values were selected as test penetrants. The protocol involved taking multiple replicate measurements of each drug's passive steady state flux through poly(dimethylsiloxane) membrane. Each penetrant's resultant permeability coefficient database was subjected to a Kolmogorov-Smirnov (KS) test for normality. It was found that the permeability coefficients of all five drugs were distributed in a Gaussian-normal fashion. The theoretical significance and practical impact of these findings are discussed.
Original languageEnglish
Pages (from-to)434-439
Number of pages5
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume67
Issue number2
DOIs
Publication statusPublished - 2007

Keywords

  • testosterone
  • oestradiol
  • corticosterone
  • aldosterone
  • adenosine
  • permeability coefficient
  • variability
  • Gaussian distribution
  • normal distribution

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