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Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach

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Abstract

The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of −26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.

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References

  1. Svejgaard E, Nilsson J. Onychomycosis in Denmark: prevalence of fungal nail infection in general practice. Mycoses. 2004;47(3–4):131–5

    Article  CAS  PubMed  Google Scholar 

  2. Faergemann J, Baran R. Epidemiology, clinical presentation and diagnosis of onychomycosis. Br J Dermatol. 2003;149(s65):1–4

    Article  PubMed  Google Scholar 

  3. Yenişehirli G, Bulut Y, Sezer E, Günday E. Onychomycosis infections in the middle black sea region, Turkey. Int J Dermatol. 2009;48(9):956–9

    Article  PubMed  Google Scholar 

  4. Garg A, Venkatesh V, Singh M, Pathak KP, Kaushal GP, Agrawal SK. Onychomycosis in central India: a clinicoetiologic correlation. Int J Dermatol. 2004;43(7):498–502

    Article  PubMed  Google Scholar 

  5. Thomas J, Jacobson G, Narkowicz C, Peterson G, Burnet H, Sharpe C. Toenail onychomycosis: an important global disease burden. J Clin Pharm Ther. 2010;35(5):497–519

    Article  CAS  PubMed  Google Scholar 

  6. Tosti A, Elewski BE. Treatment of onychomycosis with efinaconazole 10% topical solution and quality of life. J Clin Aesthet Dermatol. 2014;7(11):25–30

    PubMed  PubMed Central  Google Scholar 

  7. Lipner SR, Scher RK. Management of onychomycosis and co-existing tinea pedis. J Drugs Dermatol. 2015;14(5):492–4

    CAS  PubMed  Google Scholar 

  8. Welsh O, Vera-Cabrera L, Welsh E. Onychomycosis. Clin Dermatol. 2010;28(2):151–9

    Article  PubMed  Google Scholar 

  9. Mayo TT, Cantrell W. Putting onychomycosis under the microscope. Nurse Pract. 2014;39(5):8–11

    Article  PubMed  Google Scholar 

  10. Elewski B. Onychomycosis. Treatment, quality of life, and economic issues. Am J Clin Dermatol. 1999;1(1):19–26

    Article  Google Scholar 

  11. Gupta AK, Drummond-Main C, Cooper EA, Brintnell W, Piraccini BM, Tosti A. Systematic review of nondermatophyte mold onychomycosis: diagnosis, clinical types, epidemiology, and treatment. J Am Acad Dermatol. 2012;66(3):494–502

    Article  PubMed  Google Scholar 

  12. Monod M, Bontems O, Zaugg C, Léchenne B, Fratti M, Panizzon R. Fast and reliable PCR/sequencing/RFLP assay for identification of fungi in onychomycoses. J Med Microbiol. 2006;55(9):1211–6

    Article  CAS  PubMed  Google Scholar 

  13. Sigurgeirsson B, Olafsson J, Steinsson J, Kerrouche N, Sidou F. Efficacy of amorolfine nail lacquer for the prophylaxis of onychomycosis over 3 years. J Eur Acad Dermatol Venereol. 2010;24(8):910–5

    Article  CAS  PubMed  Google Scholar 

  14. Shemer A, Nathansohn N, Trau H, Amichai B, Grunwald MH. Ciclopirox nail lacquer for the treatment of onychomycosis: an open non-comparative study. J Dermatol. 2010;37(2):137–9

    Article  PubMed  Google Scholar 

  15. Elsayed MM. Development of topical therapeutics for management of onychomycosis and other nail disorders: a pharmaceutical perspective. J Control Release. 2015;199:132–44

    Article  CAS  PubMed  Google Scholar 

  16. Baran R, Sigurgeirsson B, Berker DD, Kaufmann R, Lecha M, Faergemann J, et al. A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement. Br J Dermatol. 2007;157(1):149–57

  17. Hartmane I, Dervenice A, Mailland F, Mikazans I, Frisenda L, Caserini M. Evaluation of safety profile, pharmacokinetics, and clinical benefit of an innovative terbinafine transungual solution (P-3058): a phase I study in patients with mild-to-moderate distal subungual onychomycosis. J Am Acad Dermatol. 2013;68(4):AB105

    Google Scholar 

  18. Pai R, Devi K. Lamivudine liposomes for transdermal delivery-formulation, characterization, stability and in vitro evaluation. Int J Pharm Sci Nanotechnol. 2009;1:317–26

    CAS  Google Scholar 

  19. Moghimipour E, Handali S. Utilization of thin film method for preparation of celecoxib loaded liposomes. Adv Pharm Bull. 2012;2(1):93–8

    PubMed  PubMed Central  Google Scholar 

  20. Chetanachan P, Akarachalanon P, Worawirunwong D, Dararutana P, Bangtrakulnonth A, Bunjop M. Ultrastructural characterization of liposomes using transmission electron microscope. Adv Mater Res. 2008;55:709–11

    Article  Google Scholar 

  21. Mohammadi-Samani S, Montaseri H, Jamshidnejad M. Preparation and evaluation of cyproterone acetate liposome for topical drug delivery. Iran J Pharm Sci. 2009;5(4):199–204

    CAS  Google Scholar 

  22. Padamwar MN, Pokharkar VB. Development of vitamin loaded topical liposomal formulation using factorial design approach: drug deposition and stability. Int J Pharm. 2006;320(1):37–44

    Article  CAS  PubMed  Google Scholar 

  23. Taghizadeh SM, Bajgholi S. A new liposomal-drug-in-adhesive patch for transdermal delivery of sodium diclofenac. J Biomater Nanobiotechnol. 2011;2:576–81

    Article  CAS  Google Scholar 

  24. Nie Y, Ji L, Ding H, Xie L, Li L, He B, et al. Cholesterol derivatives based charged liposomes for doxorubicin delivery: preparation, in vitro and in vivo characterization. Theranostics. 2012;2(11):1092–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Maestrelli F, González-Rodríguez ML, Rabasco AM, Mura P. Effect of preparation technique on the properties of liposomes encapsulating ketoprofen–cyclodextrin complexes aimed for transdermal delivery. Int J Pharm. 2006;312(1):53–60

    Article  CAS  PubMed  Google Scholar 

  26. Xu X, Khan MA, Burgess DJ. A quality by design (QbD) case study on liposomes containing hydrophilic API: I. Formulation, processing design and risk assessment. Int J Pharm. 2011;419(1):52–9

    Article  CAS  PubMed  Google Scholar 

  27. Pandey AP, Karande KP, Sonawane RO, Deshmukh PK. Applying quality by design (QbD) concept for fabrication of chitosan coated nanoliposomes. J Liposome Res. 2014;24(1):37–52

    Article  CAS  PubMed  Google Scholar 

  28. Patel HK, Shah CV, Shah VH, Upadhyay UM. Factorial designing, development and in-vitro evaluation of liposomal gel for topical delivery of quetiapine. Asian J Pharm Sci. 2012;7(4):290–302

    Google Scholar 

  29. Moghddam SRM, Ahad A, Aqil M, Imam SS, Sultana Y. Formulation and optimization of niosomes for topical diacerein delivery using 3-factor, 3-level Box-Behnken design for the management of psoriasis. Mater Sci Eng C. 2016;69:789–97

    Article  CAS  Google Scholar 

  30. Neha VM, Namita TM, Srendran CS, Viral SH. Formulation optimization and evaluation of liposomal gel of prednisolone by applying statistical design. Indian J Res Pharm Biotechnol. 2013;1(2):180

    Google Scholar 

  31. Solanki AB, Parikh JR, Parikh RH. Formulation and optimization of piroxicam proniosomes by 3-factor, 3-level Box-Behnken design. AAPS PharmSciTech. 2007;8(4):43–9

    Article  PubMed Central  Google Scholar 

  32. Henry-Michelland S, Ter-Minassian-Saraga L, Poly P, Delattre J, Puisieux F. Lyophilization and rehydration of liposomes. Colloids Surf. 1985;14(3–4):269–76

    Article  CAS  Google Scholar 

  33. Hui X, Chan TC, Barbadillo S, Lee C, Maibach HI, Wester RC. Enhanced econazole penetration into human nail by 2-n-nonyl-1, 3-dioxolane. J Pharm Sci. 2003;92(1):142–8

    Article  CAS  PubMed  Google Scholar 

  34. Ezović A, Hadžović S, Hadzidedić Š, Kostić S. Characterization of antifungal nail lacquer formulations containing fluconazole. Sci Pharm. 2010;78(3):624

    Article  Google Scholar 

  35. Ghannoum MA, Long L, Pfister WR. Determination of the efficacy of terbinafine hydrochloride nail solution in the topical treatment of dermatophytosis in a guinea pig model. Mycoses. 2009;52(1):35–43

    Article  PubMed  Google Scholar 

  36. Monti D, Saccomani L, Chetoni P, Burgalassi S, Senesi S, Ghelardi E, et al. Hydrosoluble medicated nail lacquers: in vitro drug permeation and corresponding antimycotic activity. Br J Dermatol. 2010;162(2):311–7

    Article  CAS  PubMed  Google Scholar 

  37. Patel D, Jobanputra A, Shah V. A concise review on transungual: a novel drug delivery stratergy across nails. Int Res J Humani Eng Pharm Sci. 2014;2(8):1–10

    Google Scholar 

  38. Sudaxshina M. Design of antifungal nail lacquer formulations containing antifungal. Sci Pharm. 2012;6(2):918–22

    Google Scholar 

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Authors and Affiliations

  1. Drug Discovery Lab, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Opp. To Air force Station, Palaj, Gandhinagar, Gujarat, 382355, India

    Viral H. Shah & Amee Jobanputra

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  1. Viral H. Shah
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  2. Amee Jobanputra
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Correspondence to Viral H. Shah.

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Shah, V.H., Jobanputra, A. Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach. AAPS PharmSciTech 19, 213–224 (2018). https://doi.org/10.1208/s12249-017-0831-0

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  • DOI: https://doi.org/10.1208/s12249-017-0831-0

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