Zarmpi, P; Tsikritsis, D; Belsey, N A; Rantou, E; Ghosh, P; Bunge, A L; Watson, A C; Woodman, T J; Begoña Delgado-Charro, M; Guy, R H (2026) Raman-assessed cutaneous pharmacokinetics of doxepin topical products. International Journal of Pharmaceutics, 693. 126680 ISSN 03785173

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Abstract

Identification of regulatory science tools to facilitate and accelerate accessibility to complex generic drug products continues to be the focus of significant research activity. The application of confocal Raman spectroscopy to the assessment of cutaneous drug pharmacokinetics is a particular example and has been exploited here to compare two approved creams (the reference-listed product and a generic) of doxepin hydrochloride with an intentionally non-equivalent, laboratory-made solution of the drug. Experiments involved administration of the formulations to porcine skin in vitro for 6 or 12 hours (the uptake phase) followed by 2 and 4 hours of clearance to generate Raman-assessed absorption-elimination profiles at nominal depths of 5 μm and 25 μm into the skin. This was achieved, despite overlap between spectral features of the drug with those from the skin, using a background signal removal strategy that also allowed the two functional excipients of the laboratory-made solution to be independently tracked. The areas under the Raman signal versus time absorption-elimination profiles showed (as expected) that the two creams were very similar but that the laboratory-made solution was distinctly different. First-order elimination rate constants describing the clearance phase post-application of doxepin from the superficial skin layers into the deeper tissue were also derived from the spectral data. While the experimental design was insufficiently powered to establish bio(in)equivalence to the typical regulatory standard, the data background signal separation paradigm notably expands the potential value of the approach to a broader range of chemical species than had been originally envisaged.

Item Type:	Article
Keywords:	Raman spectroscopy; Cutaneous pharmacokinetics; Topical drug bioavailability; Topical drug product bioequivalence; Regulatory science
Subjects:	Nanoscience > Surface and Nanoanalysis
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1016/j.ijpharm.2026.126680
Last Modified:	14 Sep 2026 13:20
URI:	https://eprintspublications.npl.co.uk/id/eprint/10519