Campbell UniversityCU FIND

Pharmaceutical Sciences Pharmacy and Health Sciences, College of

2019

Formulation, Optimization and TransungualPenetration Study of an Antifungal Nail PolishContaining 1% ItraconazoleSukanya Nagfernandes

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RESEARCH POSTER PRESENTATION DESIGN © 2015

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A lion’s share of the Onychomycosis is caused by Trichophyton. rubrum. The prevalence of onychomycosis is 50% in a population of patients suffering from nail disorders. It is known to have an incidence of 10-40% in a population and accounts for about 80% of overall fungal infections.Abnormal nail thickening and a substantial nail plate discoloration are manifestations of Onychomycosis.

INTRODUCTION

Inclusion of Salicylic acid, Papain and Urea in an Itraconazole (1%) nail lacquer will have the highest transungual penetration on application to the nail plate.

HYPOTHESIS

SOLVENT SYSTEM : BUTYL ACETATE, ETHYL ACETATE, ISOPROPYL ALCOHOL (70%)

ACTIVE PHARMACEUTICAL INGREDIENT (API) : ITRACONAZOLE (ITR)

PENETRATION ENHANCERS: UREA, SALICYLIC ACID, PAPAIN

STABILIZERS: CITRIC ACID (0.1N), SPAN 80

MARKETED LACQUER: SALLY HANSEN ULTIMATE SHIELD BASE & TOP COAT ™

CONCLUSION

RESULTS AND DISCUSSION Drying time

REFERENCE

To formulate, optimize and evaluate an antifungal nail lacquer, containing Itraconazole as the active pharmaceutical ingredient, which when applied topically onto the dorsal surface of the nail

plate will facilitate the transungual penetration. Compare four different formulations of Itraconazole (1%w/w) nail lacquer containing combinations of penetration enhancers

(Urea, Salicylic acid, Papain) for transungual penetration through nail plate.

To conduct an invitro, transungual penetration study on the formulations using a custom-made nail-Franz Cell

METHODOLOGY

Author: Sukanya Nagfernandes |Research Advisor: Dr. Mali R Gupta | Research Committee: Dr. Antoine Al-Achi, Mr. Paul Johnson

Formulation, Optimization and Transungual Penetration Study of anAntifungal Nail Polish Containing 1% Itraconazole

Age is an inevitable predisposing factorfor Onychomycosis, however conditionssuch as diabetes, HIV infection,immunosuppression, presence ofathlete’s foot, obesity, smoking, outdoorrecreational activities and tight clothingalso prevail.

Mechanical enhancement

• Abrasion, Avulsion, Physical enhancement, Acid Etching, Microporation, Micro needle, Microsurgical laser, Ultra-Violet (UV) light, Hydration Occlusion, Carbon dioxide laser, Photodynamic therapy, Low frequency ultra sound (Sonophoresis/Phonophoresis), Pulsed lasers, Iontophoresis

Chemical enhancement

• Thiols/ Mercaptans , Hydrogen peroxide, Urea, Hydration and Occlusion, Keratolytic Enzymes (Keratinase), Keratolytic enhancers (Papain and Salicylic acid),SEPA® (2-n-nonyl-1,3-dioxolane)

Current strategies to deal with Onychomycosis can comprehensively be classified into the following categories

The nail plate is a rigid, keratinized structure comprising of around 80-90 sheets of dead flattened. Water content: 9-35%Lipid content: 0.1-1%Disulfide linkage: 10.60%Max swelling capacity: 25%Water loss rate: 1.94 mg/cm2 /h

A medicated nail lacquer is an effective, patient convenient and aesthetic drug delivery system to treat nail fungal infections.

An antifungal nail polish containingItraconazole 1% will be put to test for its transungual penetration.

It is a BCS (Biopharmaceutical Classification System) class II drug.

OBJECTIVE

SpreadabilityAll the sets of formulation under test and the reference marketednail lacquer, will be poured onto two different glass slides at thesame inclination.A stopwatch will be used to keep time for the two samples to reachthe end of the slide.

Check for precipitation

NO PRECIPITATION UNDER MICROSCOPE

Analysis for drug content: High Performance Liquid Chromatography (HPLC)

Transungual penetration

Accelerated stability: As per ICH guidelines (40◦C ± 2◦C/ 75 % ± 5 % RH) for seven days in a stability chamber.

Statistical data analysis One-way ANOVA based on the data obtained from thetransungual penetration studies. A Post hoc test will beconducted using the Tukey HSD test. A proof of concept will beexecuted to establish reproducibility.

Table no.5: Drying time for Sally Hansen Ultimate Shield Base & Top Coat ™Nail clipping Drying time 1 2min 16 sec 68 microsec2 2min 18 sec 34 microsec3 2min 20 sec 48 microsec

Inference: A drying time of not more than 5 minutes was set as a target for the formulation under examination.

Inference: the drug was not soluble at a concentration (1%w/w) when incorporated directly in the marketed top coat vehicle.

Trial Formulation with all three enhancersButyl acetate 6.6%v/wEthyl acetate 30.50%v/wIsopropyl alcohol 70% 17.50%v/w

Itraconazole 1%w/wSalicylic acid 5%w/wPapain 5%w/wUrea 2.80%w/wTop coat Quantity sufficient

Adjustment of pH of the formulation within an optimum range of 5-6 and incorporation of Span 80 if

needed will improve desirability and stability of the formulation alongside maintaining pharmacological

activity. Research is currently in process

SET 1: Solvent system + API + Marketed lacquer + Stabilizers

SET 2: Solvent system + API + Urea + Salicylic acid + Papain + Marketed lacquer + Stabilizers

SET 3: Solvent system + API + Urea + Marketed lacquer + Stabilizers

SET 4: Solvent system + API + maximum desirability concentration from prediction profiler of a DoE conducted with Span 80, Papain and Salicylic acid as factors and drug diffused as the outcome + Marketed lacquer + Stabilizers

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2. Murdan, S. (2008). Enhancing the nail permeability of topically applied drugs. Expert Opinion on Drug Delivery,5(11), 1267-1282. doi:10.1517/17425240802497218

3. Pal, P., Thakur, R. S., Ray, S., & Mazumder, B. (2014). Design and development of a safer non-invasive transungual drug delivery system for topical treatment of onychomycosis. Drug Development and Industrial Pharmacy,41(7), 1095-1099. doi:10.3109/03639045.2014.931966

4. Quintanar-Guerrero, D., Ganem-Quintanar, A., Tapia-Olguin, P., Kalia, Y. N., & Buri, P. (1998). The Effect of Keratolytic Agents on the Permeability of Three Imidazole Antimycotic Drugs Through the Human Nail. Drug Development and Industrial Pharmacy,24(7), 685-690. doi:10.3109/03639049809082373

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6. Shanbhag, P. P., & Jani, U. (2017). Drug delivery through nails: Present and future. European Journal of Molecular & Clinical Medicine,3(5), 252. doi:10.1016/j.nhtm.2017.01.002

Additional references upon request