Raman Spectroscopic Tools to Probe the Skin−(Trans)dermal Formulation Interface

Hazel Garvie-Cook, Magdalena Hoppel, Richard Guy

Research output: Contribution to journalArticlepeer-review

4 Citations (SciVal)

Abstract

Medicines designed to deliver the active pharmaceutical ingredient either into or through the skin often referred to as topicals and transdermals, respectively are generally considered to be complex drug products. A particular challenge faced by these formulations is identifying a suitable method (ideally, in terms of specificity, accuracy, precision, and robustness) or combination of methods with which to assess the amount and rate of drug delivery to the target site. Significant research currently aims to identify and validate relevant and minimally invasive techniques that can be used to quantify both the levels of the drug attained within different parts of the skin and the kinetics with which the drug is taken up into the skin and cleared therefrom into the systemic circulation. Here, the application of confocal Raman microspectroscopy and imaging to interrogate events integral to the performance of topical and transdermal drug products at the formulation-skin interface is illustrated. Visualization, depth slicing, and profiling are used (a) to elucidate key chemical properties of both the delivery system and the skin that have impact on their interaction and the manner in which drug transfer from one to the other may occur, (b) for the transformation of a drug product from that manufactured into a residual phase post-application and inunction into the skin (including the potential for important changes in solubility of the active compound), and (c) for drug absorption into the skin and its subsequent "clearance"into deeper layers and beyond. Overall, the Raman tools described offer both qualitative and potentially semi-quantitative insights into topical and transdermal drug product performance and provide information useful for formulation improvement and optimization.

Original languageEnglish
Pages (from-to)4010-4016
Number of pages7
JournalMolecular Pharmaceutics
Volume19
Issue number11
Early online date6 Sept 2022
DOIs
Publication statusPublished - 7 Nov 2022

Bibliographical note

Funding Information:
The authors thank Renishaw plc for access to the RA802 Pharmaceutical Analyser and inVia Qontor microscope. Klucel LF and Eudragit RS polymers were provided gratis by the manufacturers. Valuable comments on the manuscript from Drs. Priyanka Ghosh and Sam Raney of the Office of Generic Drugs at the U.S. Food and Drug Administration are greatly appreciated. M.H. was funded by the Austrian Science Fund (FWF) Erwin-Schrödinger Fellowship J3754-B30. This project was also 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-FD004947). The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government. 1

Keywords

  • Raman imaging
  • Raman spectroscopy
  • skin bioavailability
  • topical skin formulations
  • transdermal drug delivery

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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