Journal Mobile Options
Table of Contents
Vol. 19, No. 1, 2006
Issue release date: December 2005
Skin Pharmacol Appl Skin Physiol 2006;19:17–21
(DOI:10.1159/000089139)

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

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

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.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Mondino A, Zanolo G, Giachetti C, Testaguzza F, Engels B, Wagener HH: Kinetic studies on ibuprofen in man – comparative determinations of serum concentrations and metabolites of ibuprofen following topical and oral adminstration. Med Welt 1983;34:1052–1054.
  2. Peters H, Chlud, K, Berner G, Wagener HH, Staab E, Melchiar E, Zimmermann P: Percutaneous kinetics of ibuprofen. Akt Rheumatol 1987;12:208–211.

    External Resources

  3. Berner G, Engels B, Vogtle-Junkert U: Percutaneous ibuprofen therapy with Trauma-Dolgit gel: bioequivalence studies. Drugs Exp Clin Res 1989;15:559–564.
  4. Seth PL: Percutaneous absorption of ibuprofen from different formulations. Comparative study with gel, hydrophilic ointment and emulsion cream. Arzneimittelforschung 1993;43:919–921.
  5. Arendtnielsen L, Drewes AM, Svendsen L, Brennum J: Quantitative assessment of joint pain following treatment of rheumatoid-arthritis with ibuprofen cream. Scand J RheumatoI 1994;23:334–337.
  6. Nasonova VA, Mravyev YV, Nasonov YL, Lebedeva W, Tsvetkova YS, Chichasova NV, Badokin W, Lesnyak OM, Demin M, Baranova EY, Korshunov NI, Mitrofanov VA, Zhadenov II, Krasilnikov AP: Local application of Dolgit cream in patients with osteoarthritis: multicenter study of efficacy and tolerance. Ter Arkiv 1995;67:48–50.
  7. Kleinbloesem CH, Ouwerkerk M, Spitznagel W, Wilkinson FE, Kaiser RR: Pharmacokinetics and bioavailability of percutaneous ibuprofen. Arzneimittelforschung 1995;45:1117–1121.
  8. Dominkus M, Nicolakis M, Kotz R, Wilkinson FE, Kaiser RR, Chlud K: Comparison of tissue and plasma levels of ibuprofen after oral and topical administration. Arzneimittelforschung 1996;46:1138–1143.
  9. Nasonova A, Muravyev YV, Kuzmina NN: Can local therapy of the joint syndrome with dolgit cream be used as an alternative to systemic nonsteroidal antiinflammatory drugs in rheumatic diseases? Ter Arkiv 1998;70:64–66.

    External Resources

  10. Tegeder I, Muth-Selbach U, Lotsch J, Rusing G, Oelkers R, Brune K, Meller S, Kelm GR, Sorgel F, Geisslinger G: Application of microdialysis for the determination of muscle and subcutaneous tissue concentrations after oral and topical ibuprofen administration. Clin Pharmacol Ther 1999;65:357–368.
  11. Rovensky J, Micekova D, Gubzova Z, Fimmers R, Lenhard G, Vogtle-Junkert U, Schreyger F: Treatment of knee osteoarthritis with a topical non-steroidal anti-inflammatory drug. Results of a randomized, doubleblind, placebo-controlled study on the efficacy and safety of a 5% ibuprofen cream. Drug Exp Clin Res 2001;27:209–221.
  12. Steen AE, Reeh PW, Geisslinger G, Steen KH: Plasma levels after peroral and topical ibuprofen and effects upon low pH-induced cutaneous and muscle pain. Eur J Pain 2000;4:195–209.
  13. Machen J, Whitefield M: Efficacy of a proprietary ibuprofen gel in soft tissue injuries: a randomised, double-blind, placebo-controlled study. Int J Clin Pract 2002;56:102–106.
  14. Whitefield M, O’Kane CJA, Anderson S: Comparative efficacy of a proprietary topical ibuprofen gel and oral ibuprofen in acute soft tissue injuries: a randomised double-blind study. J Clin Pharm Ther 2002;27:409–417.
  15. Hadgraft J, Whitefield M, Rosher PH: Skin penetration of topical formulations of ibuprofen 5%: an in vitro comparative study. Skin Pharmacol Appl Skin PhysioI 2003;16:137–142.
  16. Stott PW, Williams AC, Barry BW: Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen. J Cont Rei 1998;50:297–308.
  17. Woolfson AD, Malcolm RK, Campbell K, Jones DS, Russell JA: Rheological, mechanical and membrane penetration properties of novel dual drug systems for percutaneous delivery. J Cont Rei 2000;67:395–408.
  18. Morimoto Y, Hayashi T, Kawabata S, Seki T, Sugibayashi K: Effect of 1-menthol-ethanol-water system on the systemic absorption of flurbiprofen after repeated topical application in rabbits. Biol Pharm Bull 2000;23:1254–1257.
  19. Katayama K, Matsui R, Hatanaka T, Koizumi T: Effect of pH on skin permeation enhancement of acidic drugs by I-menthol-ethanol system. Int J Pharm 2001;226:69–80.
  20. Fujii M, Takeda Y, Yoshida M, Utoguchi N, Matsumoto M, Watanabe Y: Comparison of skin permeation enhancement by 3-I-menthoxypropane-1,2-diol and I-menthol: the permeation of indomethacin and antipyrine through Yucatan micropig skin and changes in infrared spectra and X-ray diffraction patterns of stratum corneum. Int J Pharm 2003;258;217–223.
  21. OECD guideline for the testing of chemicals. Skin absorption: in vitro method 428. 13 April 2004.
  22. Cross SE, Megwa SA, Benson HAE, Roberts MS: Self promotion of deep tissue penetration and distribution of methylsalicylate after topical application. Pharm Res 1999;16:427–433.
  23. Boutsiouki P, Thompson JP, Clough GF: Effects of local blood flow on the percutaneous absorption of the organophosphorus compound malathion: a microdialysis study in man. Archiv Toxicol 2001;75:321–328.
  24. Morgan CJ, Renwick AG, Friedmann PS: The role of stratum corneum and dermal microvasculature perfusion in penetration and tissue levels of water-soluble drugs investigated by microdialysis. Br J Dermatol 2003;148:434–443.
  25. Eccles R: Menthol and related cooling compounds. J Pharm Pharmacol 1994;46:618–630.
  26. Hong CZ, Shellock FG: Effects of a topically applied counterirritant (Eucalyptomint) on cutaneous blood flow and on skin and muscle temperatures. Am J Phys Med Rehabil 1991;70:29–33.
  27. Rainsford KD: The ever-emerging anti-inflammatories. Have there been any real advances? J Physiol (Paris) 2001;95:11–19.
  28. Pao-Chu Wu, Jin-Sheng Chang, Yaw-Bin Huang, Chee-Yin Chai, Yi-Hung Tsai: Evaluation of percutaneous absorption and skin irritation of ketoprofen through rat skin: in vitro and in vivo study. Int J Pharm 2001;222:225–235.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50