Evaluation of the bioavailability of drugs intended to act within the skin following the application of complex topical products requires the application of multiple experimental tools, which must be quantitative, validated, and, ideally and ultimately, sufficiently minimally invasive to permit use in vivo. The objective here is to show that both infrared (IR) and Raman spectroscopies can assess the uptake of a chemical into the stratum corneum (SC) that correlates directly with its quantification by the adhesive tape-stripping method. Experiments were performed ex vivo using excised porcine skin and measured chemical disposition in the SC as functions of application time and formulation composition. The quantity of chemicals in the SC removed on each tape-strip was determined from the individually measured IR and Raman signal intensities of a specific molecular vibration at a frequency where the skin is spectroscopically silent and by a subsequent conventional extraction and chromatographic analysis. Correlations between the spectroscopic results and the chemical quantification on the tape-strips were good, and the effects of longer application times and the use of different vehicles were clearly delineated by the different measurement techniques. Based on this initial investigation, it is now possible to explore the extent to which the spectroscopic approach (and Raman in particular) may be used to interrogate chemical disposition deeper in the skin and beyond the SC.

Original languageEnglish
Pages (from-to)2527-2535
Number of pages9
JournalMolecular Pharmaceutics
Issue number5
Early online date13 Apr 2023
Publication statusPublished - 1 May 2023

Bibliographical note

Funding Information:
This project was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award (1-U01-FD006533) totalling $1.25 M with 100% funded by FDA]/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government. Valuable insights from and stimulating discussions with Drs. Priyanka Ghosh, Sam Raney and Markham Luke from the FDA’s Office of Generic Drugs, and with Dr. Alex Shard from the National Physical Laboratory (U.K.) are gratefully acknowledged.


  • drug uptake into skin
  • infrared spectroscopy
  • Raman spectroscopy
  • skin penetration
  • stratum corneum sampling

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


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