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AAPS PharmSciTech

, Volume 10, Issue 2, pp 559–565 | Cite as

Development of Novel Microemulsion-Based Topical Formulations of Acyclovir for the Treatment of Cutaneous Herpetic Infections

Research Article

Abstract

The present investigation aims at developing microemulsion-based formulations for topical delivery of acyclovir. Various microemulsions were developed using isopropyl myristate/Captex 355/Labrafac as an oil phase, Tween 20 as surfactant, Span 20 as cosurfactant, and water/dimethylsulfoxide (1:3) as an aqueous phase. Transcutol, eucalyptus oil, and peppermint oil were used as permeation enhancers. In vitro permeation studies through laca mice skin were performed using Franz diffusion cells. The optimum formulation containing 2.5% Transcutol as the penetration enhancer showed 1.7-fold enhancement in flux and permeation coefficient as compared to marketed cream and ointment formulation. In vivo antiviral studies were performed in female Balb/c mice against induced herpes simplex virus I infection. A single application of microemulsion formulation containing 2.5% Transcutol given 24 h post-injection resulted in complete suppression of development of herpetic skin lesions.

KEY WORDS

acyclovir antiviral herpes simplex virus microemulsion topical 

Notes

Acknowledgments

The authors gratefully acknowledge the gift sample of ACV supplied by Arochem Industries (Mumbai, India), Captex 355 EP/NF (Abitec Corporation, UK), and Labrafac CC and Transcutol (Colorcon Asia Pvt. Ltd., India). Authors also thank Prof. Radha Kanta Ratho (Head) and Assistant Prof. Mini P. Singh, Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India for their help and guidance and for providing laboratory facilities for antiviral studies.

References

  1. 1.
    Fiddian P, Yeo JM, Clark AE. Treatment of herpes labialis. J Infect. 1983;6:41–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Freeman DJ, Sheth NV, Spruance SL. Failure of topical acyclovir in ointment to penetrate human skin. Antimicrob Agents Chemother. 1986;29:730–2.PubMedGoogle Scholar
  3. 3.
    Parry GE, Dunn P, Shah VP, Pershing LK. Acyclovir bioavailability in human skin. J Invest Dermatol. 1992;98:856–63.PubMedCrossRefGoogle Scholar
  4. 4.
    Chikhale P, Bodor N. Improved delivery of acyclovir to the skin using a dihydrotrigonelline trigonelline REDOX carrier. J Pharm Sci. 1991;80:801–2.CrossRefGoogle Scholar
  5. 5.
    Lawrence MJ, Rees GD. Microemulsion based media as novel drug delivery systems. Adv Drug Del Rev. 2000;45:89–121.CrossRefGoogle Scholar
  6. 6.
    Peltola S, Savolainen P, Keisvaara J, Suhonen TM, Urtti A. Microemulsions for topical delivery of estradiol. Int J Pharm. 2003;254:99–107.PubMedCrossRefGoogle Scholar
  7. 7.
    Aulton ME. Dissolution and solubility. In: Aulton ME, editor. Pharmaceutics. Edinburgh, UK: Churchill Livingstone; 2002. p. 15–32.Google Scholar
  8. 8.
    British Pharmacopoeia, Vol. II. The stationary Office, London; 1999, p. A-87.Google Scholar
  9. 9.
    Jain S, Jain P, Jain NK, Umamaheshwari RB. Transfersomes—a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation. Drug Dev Ind Pharm. 2003;29:1013–26.PubMedCrossRefGoogle Scholar
  10. 10.
    Piret J, Desormeaux A, Gourde AP, Juhasz J, Bergeron MG. Efficacies of topical formulations of foscarnet and acyclovir and of 5-percent acyclovir ointment (Zovirax) in a murine model of cutaneous herpes simplex virus type 1 infection. Antimicrob Agents Chemother. 2000;44:30–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Schimdt NJ. Cell culture techniques for diagnostics virology. In: Lennette EH, Schimdt NJ, editors. Diagnostic procedure for viral, rickettisial and chlamydial infections. Washington: American Public Health Association; 1979. p. 100–4.Google Scholar
  12. 12.
    Kurokawa M, Basnet P, Ohsugi M, Hozumi T, Kadota S, Namba T, Kawana T, Shiraki K. Anti-herpes simplex virus activity of moronic acid purified from Rhus javanica in vitro and in vivo. J Pharmacol Exp Ther. 1999;289:72–8.PubMedGoogle Scholar
  13. 13.
    Davis SS, Hadgraft J, Al-Khamis K. Percutaneous absorption of methyl salicylate from polyethylene glycol vehicles. J Pharm Pharmacol. 1981;33:97P.Google Scholar
  14. 14.
    Hadgraft J. Percutaneous absorption: Possibilities and problems. Int J Pharm. 1983;16:255–70.CrossRefGoogle Scholar
  15. 15.
    Barret W, Hadgraft JW, Sarnaky I. The influence of vehicles on skin penetration. J Pharm Pharmacol. 1964;16:104T–107T.Google Scholar
  16. 16.
    Abdullah, Ping QN, Liu GH. Enhancing effect of essential oils on the penetration of 5-fluorouracil through rat skin. Yao Xue Xue Bao 1996;31:214–21.PubMedGoogle Scholar
  17. 17.
    Kaplun-Frischoff Y, Touitou E. Testosterone skin permeation enhancement by menthol through formation of eutectic with drug and interaction with skin lipids. J Pharm Sci. 1997;86:1394–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Ganem-Quintanar, Lafforgue AC, Falson-Rieg F, Buri P. Evaluation of the transepidermal permeation of diethyleneglycol monoethylether and skin water loss. Int J Pharm. 1997;147:165–72.CrossRefGoogle Scholar
  19. 19.
    Godwin A, Kim NH, Felton LA. Influence of Transcutol CG on the skin accumulation and transepidermal permeation of ultraviolet absorbers. Eur J Pharm Biopharm. 2002;53:23–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang F, Kief E. Viral diseases. In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL, editors. Harrison’s principles of internal medicine. Singapore: McGraw-Hill; 1998. p. 1076–85.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  1. 1.University Institute of Pharmaceutical SciencesPanjab UniversityChandigarhIndia

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