Film drying and complexation effects in the simultaneous skin permeation of ketoprofen and propylene glycol from simple gel formulations

Bowen, Jenna L. ORCID: https://orcid.org/0000-0003-1964-6832 and Heard, Charles Martin ORCID: https://orcid.org/0000-0001-9703-9777 2006. Film drying and complexation effects in the simultaneous skin permeation of ketoprofen and propylene glycol from simple gel formulations. International Journal of Pharmaceutics 307 (2) , pp. 251-257. 10.1016/j.ijpharm.2005.10.014

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Abstract

This work investigated the simultaneous permeation of ketoprofen and propylene glycol (PG) across pig ear skin from simple gel formulations administered under simulated in-use conditions. The aims were to quantify rates of permeation of both solvent and active, probe the effects of formulation drying and gain insight into drag/complexation interactions. Simple 3-component gels were formulated using a fixed amount of ketoprofen and hydroxypropyl cellulose thickener with decreasing content of solvent propylene glycol. Multiple finite (5 mg × 15 mg) doses were massaged over 24 h into full thickness pig ear skin in vertical Franz-type diffusion cells. The permeation of ketoprofen was inversely proportional to the content of PG, whereas the permeation of PG was directly proportional, although the amount of PG permeated was always greater than ketoprofen, even from the driest gel practically achievable. In this state, the molar ratio of PG/ketoprofen was ∼12, suggesting that this number of PG molecules constitutes the solvation cage of ketoprofen. Dragging/pulling effect extends throughout the skin and into the receptor compartment and probably the system, in an in vivo situation. Although PG may represent a worse case scenario given its well-documented skin permeation enhancement properties, it is probable that other solvents exert a similar effect on solutes across skin. A drying film will behave in different ways depending on the nature of both the thickener and solvent, where the outcomes are not readily predictable. It is important to account for the fate of all species administered from a topical formulation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Publisher:	Elsevier
ISSN:	0378-5173
Last Modified:	27 Oct 2022 09:42
URI:	https://orca.cardiff.ac.uk/id/eprint/67447

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