Non steady-state descriptions of drug permeation through stratum corneum. I. The biphasic brick-and-mortar model

Michael Heisig, Renate Lieckfeldt, Gabriel Wittum, George Mazurkevich, Geoffrey Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


Purpose. The diffusion equation should be solved for the non-steady-state problem of drug diffusion within a two-dimensional, biphasic stratum corneum membrane having homogeneous lipid and corneocyte phases. Methods. A numerical method was developed for a brick-and-mortar SC-geometry, enabling an explicit solution for time-dependent drug concentration within both phases. The lag time and permeability were calculated. Results. It is shown how the barrier property of this model membrane depends on relative phase permeability, corneocyte alignment, and comeocyte-lipid partition coefficient. Additionally, the time-dependent drug concentration profiles within the membrane can be observed during the lag and steady-state phases. Conclusions. The model SC-membrane predicts, from purely morphological principles, lag times and permeabilities that are in good agreement with experimental values. The long lag times and very small permeabilities reported for human SC can only be predicted for a highly-staggered corneocyte geometry and corneocytes that are 1000 times less permeable than the lipid phase. Although the former conclusion is reasonable, the latter is questionable. The elongated, flattened corneocyte shape renders lag time and permeability insensitive to large changes in their alignment within the SC. Corneocyte/lipid partitioning is found to be fundamentally different to SC/donor partitioning, since increasing drug lipophilicity always reduces both lag time and permeability.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalPharmaceutical Research
Issue number3
StatePublished - 1996
Externally publishedYes


  • Barrier function
  • Diffusion equation
  • Non steady-state model
  • Stratum corneum

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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