Raman spectroscopy as a tool to accelerate development of complex medicinal products

Panagiota Zarmpi; Dimitrios Tsikritsis; Andrew Watson; Jean-Luc Vorng; Vasundhara Tyagi; Natalie A. Belsey; Elena Rantou; Priyanka Ghosh; Annette L. Bunge; Tim Woodman; Begona Delgado-Charro; Richard H. Guy

doi:10.1016/j.jconrel.2025.114190

Raman spectroscopy as a tool to accelerate development of complex medicinal products

Panagiota Zarmpi, Dimitrios Tsikritsis, Andrew Watson, Jean-Luc Vorng, Vasundhara Tyagi, Natalie A. Belsey, Elena Rantou, Priyanka Ghosh, Annette L. Bunge, Tim Woodman, Begona Delgado-Charro, Richard H. Guy

Research output: Contribution to journal › Article › peer-review

3 Citations (SciVal)

Abstract

Regulatory approval of complex generic drug products that are applied topically to treat skin disease can be challenging because a standard method to assess cutaneous pharmacokinetics in vivo is not available. As a result, expensive and prolonged clinical trials are often necessary, and this has proved to be a significant disincentive to generic product development and restrictive of patient access to more affordable medicines. Here Raman spectroscopy is used to quantify the relative spatiotemporal disposition of metronidazole (a drug used to treat rosacea) within the skin and proximal to its site of pharmacological action. Analysis of the data permits pharmacokinetic metrics to be extracted and compared between different gel and solution formulations with the potential to establish bioequivalence and enable more efficient complex generic drug product development.

Original language	English
Article number	114190
Journal	Journal of Controlled Release
Volume	387
Early online date	2 Sept 2025
DOIs	https://doi.org/10.1016/j.jconrel.2025.114190
Publication status	Published - 10 Nov 2025

Data Availability Statement

Data will be made available on request.

Acknowledgements

Valuable insight from and stimulating discussions with Drs. Sam Raney and Markham Luke from the FDA's Office of Generic Drugs, and from Professor Jane White at the University of Bath, are gratefully acknowledged. NAB thanks the Community for Analytical Measurement Science for a 2020 CAMS Fellowship Award funded by the Analytical Chemistry Trust Fund.

Funding

Valuable insight from and stimulating discussions with Drs. Sam Raney and Markham Luke from the FDA's Office of Generic Drugs, and from Professor Jane White at the University of Bath, are gratefully acknowledged. NAB thanks the Community for Analytical Measurement Science for a 2020 CAMS Fellowship Award funded by the Analytical Chemistry Trust Fund . This project is 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-FD 006533 (RHG) 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 insight from and stimulating discussions with Drs. Sam Raney and Markham Luke from the FDA's Office of Generic Drugs, and from Professor Jane White at the University of Bath, are gratefully acknowledged. NAB thanks the Community for Analytical Measurement Science for a 2020 CAMS Fellowship Award funded by the Analytical Chemistry Trust Fund. This project is 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-FD 006533 (RHG) 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.

Funders	Funder number
Analytical Chemistry Trust Fund
Office of Generic Drugs
Community for Analytical Measurement Science
U.S Food and Drug Administration
U.S. Department of Health and Human Services
HHS	1-U01-FD 006533

Keywords

Cutaneous pharmacokinetics
Raman spectroscopy
Regulatory science
Topical drug bioavailability
Topical drug product bioequivalence

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.1016/j.jconrel.2025.114190Licence: CC BY

Cite this

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title = "Raman spectroscopy as a tool to accelerate development of complex medicinal products",

abstract = "Regulatory approval of complex generic drug products that are applied topically to treat skin disease can be challenging because a standard method to assess cutaneous pharmacokinetics in vivo is not available. As a result, expensive and prolonged clinical trials are often necessary, and this has proved to be a significant disincentive to generic product development and restrictive of patient access to more affordable medicines. Here Raman spectroscopy is used to quantify the relative spatiotemporal disposition of metronidazole (a drug used to treat rosacea) within the skin and proximal to its site of pharmacological action. Analysis of the data permits pharmacokinetic metrics to be extracted and compared between different gel and solution formulations with the potential to establish bioequivalence and enable more efficient complex generic drug product development.",

keywords = "Cutaneous pharmacokinetics, Raman spectroscopy, Regulatory science, Topical drug bioavailability, Topical drug product bioequivalence",

author = "Panagiota Zarmpi and Dimitrios Tsikritsis and Andrew Watson and Jean-Luc Vorng and Vasundhara Tyagi and Belsey, \{Natalie A.\} and Elena Rantou and Priyanka Ghosh and Bunge, \{Annette L.\} and Tim Woodman and Begona Delgado-Charro and Guy, \{Richard H.\}",

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doi = "10.1016/j.jconrel.2025.114190",

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T1 - Raman spectroscopy as a tool to accelerate development of complex medicinal products

AU - Zarmpi, Panagiota

AU - Tsikritsis, Dimitrios

AU - Watson, Andrew

AU - Vorng, Jean-Luc

AU - Tyagi, Vasundhara

AU - Belsey, Natalie A.

AU - Rantou, Elena

AU - Ghosh, Priyanka

AU - Bunge, Annette L.

AU - Woodman, Tim

AU - Delgado-Charro, Begona

AU - Guy, Richard H.

PY - 2025/11/10

Y1 - 2025/11/10

N2 - Regulatory approval of complex generic drug products that are applied topically to treat skin disease can be challenging because a standard method to assess cutaneous pharmacokinetics in vivo is not available. As a result, expensive and prolonged clinical trials are often necessary, and this has proved to be a significant disincentive to generic product development and restrictive of patient access to more affordable medicines. Here Raman spectroscopy is used to quantify the relative spatiotemporal disposition of metronidazole (a drug used to treat rosacea) within the skin and proximal to its site of pharmacological action. Analysis of the data permits pharmacokinetic metrics to be extracted and compared between different gel and solution formulations with the potential to establish bioequivalence and enable more efficient complex generic drug product development.

AB - Regulatory approval of complex generic drug products that are applied topically to treat skin disease can be challenging because a standard method to assess cutaneous pharmacokinetics in vivo is not available. As a result, expensive and prolonged clinical trials are often necessary, and this has proved to be a significant disincentive to generic product development and restrictive of patient access to more affordable medicines. Here Raman spectroscopy is used to quantify the relative spatiotemporal disposition of metronidazole (a drug used to treat rosacea) within the skin and proximal to its site of pharmacological action. Analysis of the data permits pharmacokinetic metrics to be extracted and compared between different gel and solution formulations with the potential to establish bioequivalence and enable more efficient complex generic drug product development.

KW - Cutaneous pharmacokinetics

KW - Raman spectroscopy

KW - Regulatory science

KW - Topical drug bioavailability

KW - Topical drug product bioequivalence

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U2 - 10.1016/j.jconrel.2025.114190

DO - 10.1016/j.jconrel.2025.114190

M3 - Article

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VL - 387

JO - Journal of Controlled Release

JF - Journal of Controlled Release

M1 - 114190

ER -

Raman spectroscopy as a tool to accelerate development of complex medicinal products

Abstract

Data Availability Statement

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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