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The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum

Goh, CF; Craig, DQ; Hadgraft, J; Lane, ME; (2017) The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum. European Journal of Pharmaceutics and Biopharmaceutics , 111 pp. 16-25. 10.1016/j.ejpb.2016.10.025. Green open access

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Abstract

Drug permeation through the intercellular lipids, which pack around and between corneocytes, may be enhanced by increasing the thermodynamic activity of the active in a formulation. However, this may also result in unwanted drug crystallisation on and in the skin. In this work, we explore the combination of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the skin. Ex vivo permeation studies of saturated solutions of diclofenac sodium (DF Na) in two vehicles, propylene glycol (PG) and dimethyl sulphoxide (DMSO), were carried out in porcine ear skin. Tape stripping and ATR-FTIR spectroscopy were conducted simultaneously to collect spectral data as a function of skin depth. Multivariate data analysis was applied to visualise and categorise the spectral data in the region of interest (1700-1500cm(-1)) containing the carboxylate (COO(-)) asymmetric stretching vibrations of DF Na. Spectral data showed the redshifts of the COO(-) asymmetric stretching vibrations for DF Na in the solution compared with solid drug. Similar shifts were evident following application of saturated solutions of DF Na to porcine skin samples. Multivariate data analysis categorised the spectral data based on the spectral differences and drug crystallisation was found to be confined to the upper layers of the skin. This proof-of-concept study highlights the utility of ATR-FTIR spectroscopy in combination with multivariate data analysis as a simple and rapid approach in the investigation of drug deposition in the skin. The approach described here will be extended to the study of other actives for topical application to the skin.

Type: Article
Title: The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ejpb.2016.10.025
Publisher version: http://dx.doi.org/10.1016/j.ejpb.2016.10.025
Language: English
Additional information: Copyright © 2016. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0. Access may be initially restricted by the publisher.
Keywords: ATR-FTIR, Crystallisation, Diclofenac sodium (PubChem CID: 5018304), Dimethyl sulphoxide (PubChem CID: 679), Multivariate data analysis, Porcine skin, Propylene glycol (PubChem CID: 1030), Stratum corneum
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/1528806
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