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Vol. 19, No. 1, 2006
Issue release date: December 2005
Skin Pharmacol Appl Skin Physiol 2006;19:17–21

The Role of Menthol in Skin Penetration from Topical Formulations of Ibuprofen 5% in vivo

Brain K.R. · Green D.M. · Dykes P.J. · Marks R. · Bola T.S.
aAn-eX Analytical Services Ltd, bDepartment of Medicine (Dermatology), UWCM/Cutest Systems Ltd, Cardiff, and cThe Mentholatum Company, Glasgow, UK

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In vivo plasma profiles from formulations containing 5% ibuprofen were compared after a single topical application in a randomised, double-blind, cross-over trial. IbuleveTM gel (Dermal Laboratories, UK) contained only ibuprofen whilst Deep ReliefTM gel (Mentholatum, UK) also contained 3% menthol. In contrast to results obtained when these products were compared under in vitro conditions, there was no statistically significant difference in vivo between delivery of ibuprofen. Estimated relative bioavailability fraction (Deep Relief gel/Ibuleve gel) from log-transformed AUC(0–24h) was 0.99 (95% CI: 0.94–1.04), estimated Cmax ratio was 0.96 (95% CI: 0.91–1.00) and estimated tmax ratio was 1.01 (95% CI: 0.81–1.20). Menthol produces local vasodilation, which reduces skin barrier function, and these data demonstrate that it is inappropriate to extrapolate from in vitro data where formulation components produce biologically-mediated enhancement of permeation which cannot be modelled ex vivo. In clinical use, these products deliver comparable amounts of ibuprofen, but only Deep Reliefgel provides the secondary immediate benefit of the direct analgesic action of menthol.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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