Formulation and Evaluation of Medicated Nail Lacquer for the Treatment of Onychomycosis

Abstract

Onychomycosis is fungal infection of toenails or fingernails caused by a fungal microbe that invades the nail. The purpose of the present investigation is to formulate and evaluate an antifungal nail lacquer for treatment of onychomycosis. These formulations require high concentration of active agents to be incorporated for effective therapy because of their low efficacy. Topical therapy would be an attractive alternative approach in the treatment of onychomycosis as it is found to be capable of overcoming most of the limitations of systemic administration and targeting the drug at its site of action, with minimum interactions and adverse effects. Ciclopirox was chosen as a model drug, the formulations were prepared with permeation enhancers Salicylic acid. Then, these lacquers were compared for drying time, nonvolatile content drug content, drug diffusion and anti -microbial studies. From Diffusion studies across artificial membrane, For 12 hours, diffusion tests were conducted on all of the formulations using an artificial membrane Formulation F6 showed percentage drug release 93.2%.Thebest nail lacquer formulation was selected based on drug diffusion trials.

Introduction

• Onychomycosis is a fungal infection of the nails (toenails or fingernails), requiring high concentrations of antifungal agents for effective treatment.

• Topical treatment (such as nail lacquer) is preferred over systemic therapy due to better targeting, fewer side effects, and improved drug delivery at the infection site.

• Human nails, apart from their protective role, can serve as drug delivery systems, particularly for conditions like onychomycosis and psoriasis.

• The nail plate comprises three layers—dorsal (hard keratin), intermediate (soft keratin), and ventral—and is rich in keratin (especially cysteine).

• Despite this potential, nail-based drug delivery (ungual system) remains under-researched.

2. Materials and Methods

A. Chemicals Used

• Active Ingredient (API): Ciclopirox

• Film Formers: Nitrocellulose, Ethyl Cellulose

• Plasticizer: Dibutyl Phthalate

• Permeation Enhancer: Salicylic Acid

• Solvents: Acetone, Ethanol

B. Instruments

• UV-Vis Spectrophotometer, FT-IR, Franz diffusion cell, pH meter, hot air oven, etc.

C. Methodology

i. Preformulation Studies

• Included physical evaluation, solubility, melting point, and determination of UV absorption max (λmax = 305 nm).

• Standard calibration curve of Ciclopirox was developed using methanol with concentrations ranging from 2–12 µg/ml.

ii. Formulation Trials

Six formulations (F1 to F6) were developed by varying:

• Ethyl Cellulose (film-former)

• Dibutyl Phthalate (plasticizer)

• Salicylic Acid (permeation enhancer)

iii. Preparation of Nail Lacquer

• Ciclopirox and nitrocellulose were mixed with ethyl cellulose and stirred.

• Additional ingredients were added and volume made up with ethanol.

• Final formulation stored in glass bottles.

D. Evaluation Parameters

• Non-volatile content

• Drying time

• Smoothness to flow

• Gloss

• Viscosity (measured using Brookfield Viscometer)

• Drug content (using UV Spectrophotometry at 305 nm)

• Diffusion studies (across artificial membranes)

• Antimicrobial activity

• Stability Studies: Conducted at 40 ± 2°C / 75 ± 5% RH for 3 months following ICH guidelines.

3. Results and Discussion

A. Preformulation Results

• Ciclopirox: White crystalline solid with characteristic odor.

• Melting Point: Observed 139°C (within reported range of 135–143°C).

• Solubility: Highest in ethanol (0.78 mg/ml), followed by acetone and water.

• λmax: 305 nm (used for drug quantification).

B. Calibration Curve and Drug Quantification

• Developed using UV-Vis spectrophotometer with good linearity in the tested range.

Conclusion

1) The purpose of the present investigation was to formulate and evaluate the Ciclopirox nail lacquer as an ungual drug delivery system for the treatment of onychomycosis. 2) Ciclopirox was chosen as a model drug, the formulations were prepared with permeation enhancers Salicylic acid. Then, these lacquers were compared for drying time, nonvolatile content drug content, drug diffusion and anti - microbial studies. 3) From the FTIR studies, it was concluded that the drug and the excipients used in the formulations were compatible with each other. 4) All formulations showed good film formation, drying time, smooth flow, and required volatile content. 5) Microbial study results proved that the formulations are sensitive to the microorganism Candida albicans. 6) The stability tests showed that the formulations were stable at 40°c for 3 month. 7) The results obtained from the in vitro studies indicate that formulation F6 showed a complete drug release which sustained over 12 hours. 8) The percentage non-volatile content of F6 formulation was found to be 36±0.40.The desired amount of non-volatile matter was seen with complete evaporationof volatile matter. 9) F6 formulation showed rapid drying rate. 10) The viscosity of F6 formulation was observed as 140.so this formulation was clear and glossy. 11) The adhesive strength of F6 formulation compared with marketed sample and it possess adequate adhesive strength on applied nail surface. 12) 99.02% of drug content was found in F6. So a good therapeutic outcome can be expected. 13) From Diffusion studies across artificial membrane, For 12 hours, diffusion tests were conducted on all of the formulations using an artificial membrane (cellophane membrane -0.8µm). Formulation F6 showed percentage drug release 93.2%. The best nail lacquer formulation was selected based on drug diffusion trials. 14) The formulation F6 was selected as the optimized nail lacquer formulation based on drug diffusion studies 15) Stability study data showed that there was no much change in the values after stability test. It was concluded that the formulations were found to possess stability compliance requirements as per ICH guidelines.

References

[1] Gupchup GV, Zatz JL. Structural characteristics and permeability properties of the human nail: A review. j Cosmet Sci 1999;50:363-385. [2] Rajendra VB, Baro A, Kumari A, Dhamecha DL, Lahoti SR, Shelke SD. Transungual Drug Delivery: An Overview. J Appl Pharm Sci 2012;2(1):203- 09 [3] Patel RP, Naik SA, Patel NA, Suthar AM. Drug delivery across human nail. Int J Curr Pharm Res Vol1Issue1 2009;01:01-7 [4] Suryavanshi KA, Basru PR, Katedeshmukh RG. Review on Nail Transungual Drug Delivery System. Am. J. PharmTech Res. 2012;2(5):222- 04. [5] Sabreen J, Divyakumar B, Kiran B. Preungual drug delivery systems of terbinafine hydrochloride nail lacquer. Asian J Pharm 2008;02:53-06. [6] Shirwaikar AA, Thomas TA, Lobo R, Prabhu KS. Treatment of Onychomycosis:An Update. Ind J Pharm Sci 2008 Nov-Dec;70(6):710-14. [7] Lalit SK, Panwar SA, Darwhaker G, Jain DK. Formulation and Evaluation of Ciclopirox Amphiphilogel. Der Pharmacia Lettre, 2011; 3 (5):125-31 [8] Kobayashi Y,Komastu T,Sumi M,Numajiri S,Miyamoto M,Kobayashi D,Sugibayashi K,Morimoto Y.In vitro permeation of several drugs through the human nail plate:Relationship between physicochemical properties and nail permeability of drugs.Eur.J.Pharm.Sci.2004;21:471-477. [9] Alam G, Singh MP, Singh A, Vishwakarma DK, Patel R, Srivastava SP. Trans- ungual drug transport: advancement and challenges. J Pharm Res 2012;5(5):2574- 79. [10] Walters,K.A, Flynn,G.L, Marvel,J.R.Peneration of the human nail plate:the effects of vehicle pH on the permeation of miconazole. J.Pharm.Pharmaco.1985;37:498- 499. [11] Pravin DC, Shilpa PC, Pramod KK, Bothiraja C. Drug delivery through nail 2006 cited 2010 Nov 29. Available from: URL: http://www.pharmainfo.net/reviews/drug- delivery-through-nail- review [12] Boni E. Elewski, Onychomycosis: Pathogenesis, Diagnosis, and Management, Clin. Microbiol. Rev. July 1998 vol. 11 no. 3 415-429 [13] Jason A. Winston , Jami L. Miller, Treatment of Onychomycosis in Diabetic Patients, Clinical.diabetesjournals.org 2008 Nov-Dec; 70(6): 710–714 [14] Westerberg DP, Voyack MJ. Onychomycosis: current trends in diagnosis and treatment. American family physician. Dec 2013. 88 (11): 762–70. [15] Weinberg JM, Koestenblatt EK, Tutrone WD, Tishler HR, Najarian L. Comparison of diagnostic methods in the evaluation of onychomycosis. J. Am. Acad. Dermatol. 2003. 49 (2): 193–7 [16] Elewski, BE; Hay, RJ. Update on the management of onychomycosis: highlights of the Third Annual International Summit on Cutaneous Antifungal Therapy. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. August 1996. 23 (2): 305–13 [17] Phillip R, And Bassler M, Treating Onychomycosis, University of Michigan Medical School, Ann Arbor, Michigan, Am Fam Physician. 2001 Feb 15;63(4):663-673. [18] Cohen PR, Scher RK. Topical and surgical treatment of onychomycosis. J. Am. Acad. Dermatol. 1994; 31:S74–S77. [19] Gupta AK, Lynde CW, Jain HC, Sibbald RG, Elewski BE, Daniel CR, Watteel GN, Summerbell RC. A higher prevalence of onychomycosis in psoriatics compared with non- psoriatics: A multicentre study. The British journal of dermatology. 1997. 136 (5): 786–789.

Copyright

Copyright © 2025 Mr. Vaibhav Narwade, Mr. Krishna Renge, Dr. Pranav Parekh, Mr. Mahesh Thakare. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.