Effects of permeation enhancers on flufenamic acid delivery in Ex vivo human skin by confocal Raman microscopy

Yelena Pyatski, Qihong Zhang, Richard Mendelsohn, Carol R. Flach

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


For effective topical delivery, a drug must cross the stratum corneum (SC) barrier into viable tissue. The use of permeation enhancers is a widespread approach for barrier modification. In the current study, flufenamic acid (FluA), a non-steroidal anti-inflammatory drug, is a model agent for investigating the influence of hydrophobic versus hydrophilic enhancers. In separate experiments, FluA in octanol or propylene glycol/ethanol (75/25) is applied to the SC for varying times followed by confocal Raman microscopic mapping of drug and enhancer penetration and spatial distribution. Deuterated versions of the enhancers permit us to spectroscopically distinguish the exogenous chemicals from the endogenous SC lipids without affecting penetration parameters. The FluA pathway is tracked by the C=C stretching mode at ∼1618 cm-1. Discrete, small inclusions of both enhancers are observed throughout the SC. High concentrations of FluA are co-localized with octanol domains which appear to provide a pathway to the viable epidermis for the drug. In contrast, FluA concentrates in the upper SC when using the hydrophilic agent and endogenous lipids appear unperturbed in regions outside the enhancer pockets. The ability to examine perturbations to endogenous ultrastructure and molecular structure in skin while tracking penetration pathways provides insight into delivery mechanisms.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - May 30 2016

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Chemical permeation enhancer
  • Confocal Raman microscopy
  • Cutaneous penetration
  • Flufenamic acid
  • Skin


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