title: The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum.
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.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia; Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: gohchoonfu@hotmail.com.
authors.forename: Choon Fu
authors.initials: CF
authors.lastname: Goh
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: duncan.craig@ucl.ac.uk.
authors.forename: Duncan Q M
authors.initials: DQ
authors.lastname: Craig
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: jonathan.hadgraft@btinternet.com.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hadgraft
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: majella.lane@btinternet.com.
authors.forename: Majella E
authors.initials: ME
authors.lastname: Lane
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D003460:Crystallization; D004008:Diclofenac / Q000737:chemistry*; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004817:Epidermis / Q000187:drug effects*; D007249:Inflammation; D008027:Light; D015999:Multivariate Analysis; D010146:Pain; D025341:Principal Component Analysis; D019946:Propylene Glycol / Q000737:chemistry; D012867:Skin / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D013552:Swine; D013816:Thermodynamics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D019946:Propylene Glycol; D004121:Dimethyl Sulfoxide
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