Original Article

Investigation on utility of some novel terpenes on transungual delivery of terbinafine for the management of onychomycosis

    Isha Gupta Bio
    ; Syeda Nashvia Adin Bio
    ; Mohd Aqil Bio
    ; Mohd Mujeeb Bio
    ; Yasmin Sultana Bio

Author Affiliation(s)


Introduction: Onychomycosis is a fungal disorder of the nail which afflicts 5% of the population worldwide. The disease is strenuous to cure as it is chronic, hard to eliminate and tends to recur. Topical therapy is at the forefront for the treatment of many disorders of nail. However, the success rate of topical therapy has been halted owing to the poor permeation of topical therapeutics across densely keratinized nail barrier. Therefore, ungual drug permeation must be improved for an effective topical therapy. An approach to achieve this goal would be the use of terpenes from natural sources as potential penetration enhancers. This study is aimed to explore the effectiveness of some novel terpenes as potential penetration enhancers on transungual delivery of terbinafine.

Methods: Ex-vivo permeation studies were performed by sopping the nail clippings of healthy human volunteers in control and working solutions containing terbinafine (5mg/ml) per se and terbinafine (5mg/ml) with 6% of each terpenes including lavandulol, safranal, rose oxide, limonene, 3-methyl-2-butene-1-ol, and linalool respectively for 48 hours. The terbinafine concentration in nail samples was determined using a HPLC method.

Results: Statistical analysis showed that studied terpenes increase transungual penetration of terbinafine in the following order: linalool > rose oxide > 3-methyl-2-butene-1-ol > safranal> limonene>lavandulol acetate. Accordingly, linalool was found to be the most effective penetration enhancer for the transungual delivery of terbinafine.

Conclusion: It is concluded that linalool can be used as safe and potential penetration enhancer for enhancing the transungual delivery of terbinafine for onychomycosis.

Keywords : Onychomycosis, transungual, terpenes, penetration enhancer, terbinafine, nail


1. Gupta AK, Stec N. Recent advances in therapies for onychomycosis and its management. F1000Res. 2019; 8:F1000 Faculty Rev-968. Published 2019 Jun 25. doi:10.12688/f1000research.18646.1 2. Lipner SR, Scher RK. Onychomycosis: Treatment and prevention of recurrence. J Am Acad Dermatol. 2019; 80(4): 853–67. 3. Gupta AK, Ryder JE, Johnson AM. Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis. Br J Dermatol. 2004; 150(3):537-544. 4. Antifungal drugs. Treat Guidel Med Lett. 2009; 7(88):95-102. 5. Bennett JE. Antifungal agents. In: Brunton L, Chabner B, Knollman B, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011:1571-1592. 6. Darkes MJ, Scott LJ, Goa KL. Terbinafine: a review of its use in onychomycosis in adults. Am J Clin Dermatol. 2003; 4(1):39-65. 7. Angelo T, Borgheti-Cardoso LN, Gelfuso GM. Chemical and physical strategies in onychomycosis topical treatment: A review. Med Mycol. 2017; 55(5): 461–475. 8. Gupta AK, Scher RK. Management of onychomycosis: a North American perspective. Dermatologic Ther. 1997; 3: 58-65' 9. Gupta AK, Scher RK, De Doncker P. Current management of onychomycosis: an overview. Derm Clinics.1997; IS: 121-13 5· 10. Gupta AK, Sauder ON, Shear NH. Antifungal agents: an overview. Part 1. ] Am Acad Dermatol. 1994; 30: 677-69 8. 11. Gupta AK, Sauder ON, Shear NH. Antifungal agents: an overview. Part II. ] Am Acad Dermatol. 1994; 30: 9 II-933· 12. Gupta AK, Scher RK. Oral antifungal agents for onychomycosis. Lancet. 1998; 351: 541-542. 13. Gupta AK, Simpson FC. Routes of drug delivery into the nail apparatus: Implications for the efficacy of topical nail solutions in onychomycosis. J Dermatolog Treat. 2016; 27(1): 2–4. 14. De Doncker P. Pharmacokinetics of oral antifungal agents. Dermatol.Ther. 1997; 3:46–57. 15. Bseiso EA, Nasr M, Sammour OA, Abd El Gawad NA. Novel nail penetration enhancer containing vesicles “nPEVs” for treatment of onychomycosis. Drug Deliv. 2015; 23: 1-7. 16. Elkeeb R, AliKhan A, Elkeeb L, Hui X, Maibach HI. Transungual drug delivery: Current status. Int J Pharm. 2010; 384(1-2): 1-8. [] [PMID: 19819318]. 17. Murdan S. Enhancing the nail permeability of topically applied drugs. Expert Opin Drug Deliv. 2008; 5(11): 1267-82. [] 18. Ahad A, Aqil M, Kohli K, Chaudhary H, Sultana Y, Mujeeb M.Chemical penetration enhancers: a patent review. Expert Opin Ther Pat. 2009; 19:969–988. 19. Murthy SN, Maibach HI. Topical nail products and ungual drug delivery. Boca Raton: C.R.C. Press 2013. 20. Ahad A, Aqil M, Kohli K, Sultana Y, Mujeeb M, Ali A. Role of novel terpenes in transcutaneous permeation of valsartan: Effectiveness and mechanism of action. Drug development and industrial pharmacy. 2011; 37, 583-96. 10.3109/03639045.2010.532219. 21. Suganthini K. Terbinafine: A pharmacological and clinical review. Expert opinion on pharmacotherapy. 2009; 10, 2723-33. 10.1517/14656560903307462. 22. Khengar RH, Jones SA, Turner RB, Forbes B, Brown MB. Nail swelling as a pre-formulation screen for the selection and optimisation of ungual penetration enhancers. Pharm. Res. 2007; 24, 2207–2212. 23. Walters KA, Abdalghafor HM, Lane ME. The human nail—Barrier characterisation and permeation enhancement. Int. J. Pharm. 2012: 435, 10–21 24. Yang F, Yu X, Shao W, Guo P, Cao S, Wang M, Wang Y, Wu C, Xu Y. Co-delivery of terbinafine hydrochloride and urea with an in situ film-forming system for nail targeting treatment. Int J Pharm. 2020 Jul 30; 585:119497. doi: 10.1016/j.ijpharm.2020.119497. Epub 2020 Jun 3. PMID: 32504773. 25. Saner MV, Kulkarni AD, Pardeshi CV. Insights into drug delivery across the nail plate barrier. J. Drug Target. 2014; 22, 769–789. 26. Abdollahi D, Jafariazar Z, Afshar M. Effect of monoterpenes on ex vivo transungual delivery of itraconazole for the management of onychomycosis. J Cosmet Dermatol. 2020; 19(10):2745-2751. Doi: 10.1111/jocd.13317. Epub 2020 Feb 11. PMID: 32043759.

Send mail to Author

Send Cancel