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Drug Delivery Letters

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ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

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Research Article

Development and Evaluation of Luliconazole Nail Lacquer Containing Potential Permeation Enhancers for an Enhanced Transungual Drug Delivery

Author(s): Preeti Chauhan, Rimpy Pahwa, Pooja Kumari, Tarun Kumar and Munish Ahuja*

Volume 13, Issue 1, 2023

Published on: 06 January, 2023

Page: [35 - 47] Pages: 13

DOI: 10.2174/2210303113666221117085703

Price: $65

Abstract

Background: Topical therapy for nail infection has a serious drawback of drug permeation via keratinized human nail plate. Onychomycosis, or tinea unguium, is a human nail fungal infection affecting nearly 19% of the world’s population.

Aim: Purposely, we aimed to develop and evaluate nail lacquer formulations incorporated with luliconazole utilizing different permeation enhancers for targeted transungual drug delivery. Nail clippings were treated with luliconazole solution (5% w/v) with or without permeation enhancers and screened by determining the hydration enhancement factor and retention of the drug in the nail clippings. Different batches of nail lacquer formulations were prepared to employ Eudragit, polyethylene glycol 400, Tween 80, and permeation enhancer with the highest hydration enhancement factor value.

Methods: Successively, the formulations were evaluated for studies like compatibility, application, gloss, blush, smoothness of flow, adhesion, non-volatile content, etc. Based on the results of physical characterization and in vitro release study, formulations based on Eudragit RLPO and RSPO containing N-acetylcysteine and urea and the Eudragit RL100 containing urea as penetration enhancer were found to be potentially useful. Furthermore, a comparative ex vivo evaluation of the formulations for permeation across the nail clippings revealed that the luliconazole-loaded Eudragit RLPO formulations containing N-acetylcysteine and urea provided the highest flux (5.12 μg/cm2/min) and shortest lag time (17.4 min).

Results: Morphological analysis showed an increase in the number of pores on the nail surface, leading to the enhancement of drug diffusion across the nail matrix and nail bed.

Conclusion: Furthermore, the luliconazole nail lacquer formulation exhibited higher antifungal activity, viscosity, and stability properties. Hence, the results suggest that the developed luliconazole nail lacquer formulation is an efficient topical transungual drug delivery system.

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Graphical Abstract

[1]
Shanbhag, P.P.; Jani, U. Drug delivery through nails: Present and future. New Horiz. Transl. Med., 2017, 3, 252-263.
[2]
Aggarwal, R.; Targhotra, M.; Sahoo, P.K.; Chauhan, M.K. Onychomycosis: Novel strategies for treatment. J. Drug Del. Sci., 2020, 57, 1-11.
[3]
Murdan, S. Drug delivery to the nail following topical application. Int. J. Pharm., 2002, 236(1-2), 1-26.
[http://dx.doi.org/10.1016/S0378-5173(01)00989-9] [PMID: 11891066]
[4]
Brown, M.; Turner, R.; Wevrett, S.R. Use of in vitro performance models in the assessment of drug delivery across the human nail for nail disorders. Expert Opin. Drug Deliv., 2018, 15(10), 983-989.
[http://dx.doi.org/10.1080/17425247.2018.1518425] [PMID: 30173543]
[5]
Shivakumar, H.N.; Vaka, S.R.K.; Satheesh Madhav, N.V.; Chandra, H.; Murthy, S.N. Bilayered nail lacquer of terbinafine hydrochloride for treatment of onychomycosis. J. Pharm. Sci., 2010, 99(10), 4267-4276.
[http://dx.doi.org/10.1002/jps.22150] [PMID: 20737634]
[6]
Akhtar, N.; Sharma, H.; Pathak, K. Onychomycosis: Potential of nail lacquers in transungal delivery of antifungals. Scientifica (Cairo), 2016, 2016, 1-12.
[http://dx.doi.org/10.1155/2016/1387936] [PMID: 27123362]
[7]
Vipin, K.V.; Sarath, C.C.; Ann, R.A.; Premaletha, K.; Kuriakose, M.R. Formulation and evaluation of an antifungual nail lacquer for onychomycosis. Br. Biomed. Bull., 2014, 2, 242-248.
[8]
Aggarwal, R.; Targhotra, M.; Sahoo, P.K.; Chauhan, M.K. Efinaconazole nail lacquer for the transungual drug delivery: Formulation, optimization, characterization and in vitro evaluation. J. Drug Deliv. Sci. Technol., 2020, 60, 101998.
[http://dx.doi.org/10.1016/j.jddst.2020.101998]
[9]
Shivakumar, H.N.; Juluri, A.; Desai, B.G.; Murthy, S.N. Ungual and transungual drug delivery. Drug Dev. Ind. Pharm., 2012, 38(8), 901-911.
[http://dx.doi.org/10.3109/03639045.2011.637931] [PMID: 22149347]
[10]
Matsuda, Y.; Sugiura, K.; Hashimoto, T.; Ueda, A.; Konno, Y.; Tatsumi, Y. Efficacy coefficients determined using nail permeability and antifungal activity in keratin-containing media are useful for predicting clinical efficacies of topical drugs for onychomycosis. PLoS One, 2016, 11(7), e0159661.
[http://dx.doi.org/10.1371/journal.pone.0159661] [PMID: 27441843]
[11]
Elkeeb, R. AliKhan, A.; Elkeeb, L.; Hui, X.; Maibach, H.I. Transungual drug delivery: Current status. Int. J. Pharm., 2010, 384(1-2), 1-8.
[http://dx.doi.org/10.1016/j.ijpharm.2009.10.002] [PMID: 19819318]
[12]
Mahtab, A.; Anwar, M.; Mallick, N.; Naz, Z.; Jain, G.K.; Ahmad, F.J. Transungual delivery of ketoconazole nanoemulgel for the effective management of onychomycosis. AAPS PharmSciTech, 2016, 17(6), 1477-1490.
[http://dx.doi.org/10.1208/s12249-016-0488-0] [PMID: 26857516]
[13]
Wiederhold, N.P.; Fothergill, A.W.; McCarthy, D.I.; Tavakkol, A. Luliconazole demonstrates potent in vitro activity against dermatophytes recovered from patients with onychomycosis. Antimicrob. Agents Chemother., 2014, 58(6), 3553-3555.
[http://dx.doi.org/10.1128/AAC.02706-13] [PMID: 24709260]
[14]
Abastabar, M.; Al-Hatmi, A.M.S.; Vafaei Moghaddam, M.; de Hoog, G.S.; Haghani, I.; Aghili, S.R.; Shokohi, T.; Hedayati, M.T.; Daie Ghazvini, R.; Kachuei, R.; Rezaei-Matehkolaei, A.; Makimura, K.; Meis, J.F.; Badali, H. Potent activities of luliconazole, lanoconazole, and eight comparators against molecularly characterized Fusarium species. Antimicrob. Agents Chemother., 2018, 62(5), e00009-e00018.
[http://dx.doi.org/10.1128/AAC.00009-18] [PMID: 29530844]
[15]
Scher, R.K.; Nakamura, N.; Tavakkol, A. Luliconazole: A review of a new antifungal agent for the topical treatment of onychomycosis. Mycoses, 2014, 57(7), 389-393.
[http://dx.doi.org/10.1111/myc.12168] [PMID: 24621346]
[16]
Jones, T.; Tavakkol, A. Safety and tolerability of luliconazole solution 10-percent in patients with moderate to severe distal subungual onychomycosis. Antimicrob. Agents Chemother., 2013, 57(6), 2684-2689.
[http://dx.doi.org/10.1128/AAC.02370-12] [PMID: 23545529]
[17]
Watanabe, S.; Kishida, H.; Okubo, A. Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study. J. Dermatol., 2017, 44(7), 753-759.
[http://dx.doi.org/10.1111/1346-8138.13816] [PMID: 28332720]
[18]
Khattab, A.; Shalaby, S. Optimized ciclopoirox-based Eudragit RLPO nail lacquer: Effect of endopeptidase enzyme as permeation enhancer on transungal drug delivery and efficiency against onchomycosis. AAPS PharmSciTech, 2018, 19(3), 1048-1060.
[http://dx.doi.org/10.1208/s12249-017-0917-8] [PMID: 29138987]
[19]
Jain, S.K.; Jain, A.K.; Rajpoot, K. Expedition of Eudragit® polymers in the development of novel drug delivery system. Curr. Drug Deliv., 2020, 17(6), 448-469.
[http://dx.doi.org/10.2174/1567201817666200512093639] [PMID: 32394836]
[20]
Thakral, S.; Thakral, N.K.; Majumdar, D.K. Eudragit®: A technology evaluation. Expert Opin. Drug Deliv., 2013, 10(1), 131-149.
[http://dx.doi.org/10.1517/17425247.2013.736962] [PMID: 23102011]
[21]
Bruno, A.; Frei, C.; Henrich, W. Pharmaceutical composition for the treatment of nail diseases., 2008.
[22]
Kataria, P.; Sharma, G.; Thakur, K.; Bansal, V.; Dogra, S.; Katare, O.P. Emergence of nail lacquers as potential transungual delivery system in the management of onchomycosis. Expert Opin. Drug Deliv., 2016, 13(7), 937-952.
[http://dx.doi.org/10.1080/17425247.2016.1174691] [PMID: 27054394]
[23]
Samour, C.M.; Krauser, S.F. Antifungal nail lacquer and method using same. Patent US 6,224,887, 2001.
[24]
Kushwaha, A.S.; Repka, M.A.; Narasimha Murthy, S. A novel apremilast nail lacquer formulation for the treatment of nail psoriasis. AAPS PharmSciTech, 2017, 18(8), 2949-2956.
[http://dx.doi.org/10.1208/s12249-017-0776-3] [PMID: 28455829]
[25]
Thatai, P.; Sapra, B. Terbinafine hydrochloride nail lacquer for the management of onychomycosis: Formulation, characterization and in vitro evaluation. Ther. Deliv., 2018, 9(2), 99-119.
[http://dx.doi.org/10.4155/tde-2017-0069] [PMID: 29325509]
[26]
Kiran, R.S.; Shekar, B.C.; Vishnu, P.; Prasad, M.V. Ungual drug delivery system of ketoconazole nail lacquer. Int. J. Appl. Pharm., 2010, 4, 9-17.
[27]
Joshi, M.; Sharma, V.; Pathak, K. Matrix based system of isotretinoin as nail lacquer to enhance transungal delivery across human nail plate. Int. J. Pharm., 2015, 478(1), 268-277.
[http://dx.doi.org/10.1016/j.ijpharm.2014.11.050] [PMID: 25445993]
[28]
Šveikauskaitė, I.; Briedis, V. Effect of film-forming polymers on release of naftifine hydrochloride from nail lacquers. Int. J. Polym. Sci.2017 2017.
[29]
Mathew, F.; Bindumol, K.C.; Paul, J.; Pathadan, R.P.; Varghese, V. Understanding our natural nail–antifungal agents. Int. J. Pharm. Pharm., 2014, 6, 918-922.
[30]
El-sherif, N.I.; Shamma, R.N.; Abdelbary, G. In-situ gels and nail lacquers as potential delivery systems for treatment of onychomycosis. A comparative study. J. Drug Deliv. Sci. Technol., 2018, 43, 253-261.
[http://dx.doi.org/10.1016/j.jddst.2017.10.018]
[31]
Ghannoum, M.; Sevin, K.; Sarkany, M. Amorolfine 5% nail lacquer exhibits potent antifungal activity compared to three acid-based devices indicated for the treatment of onychomycosis: An in vitro nail penetration assay. Dermatol. Ther. (Heidelb.), 2016, 6(1), 69-75.
[http://dx.doi.org/10.1007/s13555-016-0093-x] [PMID: 26833478]
[32]
Murdan, S. Enhancing the nail permeability of topically applied drugs. Expert Opin. Drug Deliv., 2008, 5(11), 1267-1282.
[http://dx.doi.org/10.1517/17425240802497218] [PMID: 18976136]
[33]
Kobayashi, Y.; Miyamoto, M.; Sugibayashi, K.; Morimoto, Y. Enhancing effect of N-acetyl-l-cysteine or 2-mercaptoethanol on the in vitro permeation of 5-fluorouracil or tolnaftate through the human nail plate. Chem. Pharm. Bull. (Tokyo), 1998, 46(11), 1797-1802.
[http://dx.doi.org/10.1248/cpb.46.1797] [PMID: 9845958]
[34]
van Hoogdalem, E.J.; van den Hoven, W.E.; Terpstra, I.J.; van Zijtveld, J.; Verschoor, J.S.C.; Visser, J.N. Nail penetration of the antifungal agent oxiconazole after repeated topical application in healthy volunteers, and the effect of acetylcysteine. Eur. J. Pharm. Sci., 1997, 5(3), 119-127.
[http://dx.doi.org/10.1016/S0928-0987(97)00270-4]
[35]
Haque, S.E.; Sheela, A. Miscibility of eudragit/chitosan polymer blend in water determined by physical property measurements. Int. J. Pharm., 2013, 441(1-2), 648-653.
[http://dx.doi.org/10.1016/j.ijpharm.2012.10.031] [PMID: 23107794]
[36]
Katara, R.; Majumdar, D.K. Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery. Colloids Surf. B Biointerfaces, 2013, 103, 455-462.
[http://dx.doi.org/10.1016/j.colsurfb.2012.10.056] [PMID: 23261566]
[37]
Nair, A.B.; Kim, H.D.; Chakraborty, B.; Singh, J.; Zaman, M.; Gupta, A.; Friden, P.M.; Murthy, S.N. Ungual and trans-ungual iontophoretic delivery of terbinafine for the treatment of onychomycosis. J. Pharm. Sci., 2009, 98(11), 4130-4140.
[http://dx.doi.org/10.1002/jps.21711] [PMID: 19340887]
[38]
Sintov, A.C.; Botner, S. Transdermal drug delivery using microemulsion and aqueous systems: Influence of skin storage conditions on the in vitro permeability of diclofenac from aqueous vehicle systems. Int. J. Pharm., 2006, 311(1-2), 55-62.
[http://dx.doi.org/10.1016/j.ijpharm.2005.12.019] [PMID: 16431047]
[39]
Patel, R.P.; Patel, G.; Baria, A.; Baria, A. Formulation and evaluation of transdermal patch of aceclofenac. Int. J. Drug Deliv., 2009, 1(1), 41-51.
[http://dx.doi.org/10.5138/ijdd.2009.0975.0215.01005]
[40]
Al-Ismaily, M.; Wijmans, J.G.; Kruczek, B. A shortcut method for faster determination of permeability coefficient from time lag experiments. J. Membr. Sci., 2012, 423-424, 165-174.
[http://dx.doi.org/10.1016/j.memsci.2012.08.009]
[41]
Mustapha, R.B.; Lafforgue, S.; Fenina, N.; Marty, J.P. Influence of drug concentration on the diffusion parameters of caffeine. Indian J. Pharmacol., 2011, 43(2), 157-162.
[http://dx.doi.org/10.4103/0253-7613.77351] [PMID: 21572649]

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