IN-SITU FILM-FORMING SOLUTION FOR TOPICAL APPLICATION OF TERBINAFINE HCL: BIOPHARMACEUTICAL EVALUATION AND IN VIVO ANTIFUNGAL PERFORMANCE USING ANIMAL MODEL

Nor Amlizan Ramli,Kalavathy Ramasamy,Mohd Faiz Mustaffa,Mizaton Hazizul Hasan,Aishah Adam,Suraya Suratman,Naqibah Jaafar

doi:10.22159/ijap.2021v13i6.42589

Nor Amlizan Ramli, Kalavathy Ramasamy + Show 5 more

Open Access

https://doi.org/10.22159/ijap.2021v13i6.42589

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Abstract

Objective: The main purpose of this study is to develop a film-forming solution with optimum physical-mechanical characteristics and excellent antifungal activity to enhance deposition and penetration into the stratum corneum (SC). Methods: The film-forming solutions of terbinafine HCl were formulated using methacrylate copolymers, polyethylene glycol 400, and ethanol as diluent. The selected formulations were subjected to test of physical-mechanical properties, drug release, drug permeation across the stratum corneum and drug deposition study. The best formulation was further evaluated for in vivo antifungal efficacy. Results: The selected formulations exhibited superior pharmaceutical characteristics, including rapid drying, non-stickiness, and being transparency on the skin. Formulation A (FA) had significantly lower tensile strength (4.78 N/m2, p<0.05) and higher percentage elongation at break (33.61%, p<0.05), which reduced the firmness of the film, allowing it to be super-flexible in following the movement of the skin and preventing loss of film through abrasion. FA showed significantly (p<0.05) rapid drug permeation (1510.51 µg/cm2) across the stratum corneum (SC) at 24 h when compared with the other formulations and the positive control proprietary drug (PD), Terbex® cream formulation (475.8 µg/cm2). Conclusion: Having superior physical-mechanical and drug permeation characteristics, FA can be considered as an efficient, reproducible, and efficacious antifungal formulation for topical application.

Highlights

Dermatophytosis infects more than 20%of the world population [1] and is the most frequent source of infection, especially in tropical countries [2, 3]
These infections are not life-threatening but are responsible for the largest global burden of years lived with disability (YLDs) which are higher (36.4 million) than diabetes mellitus (29.5 million) and migraine (28.9 million) [4]
The findings of this study showed that the weight and thickness of all the tested formulations passed the requirement for uniformity except the uniformity of thickness of formulation C (FC)

Summary

Introduction

Dermatophytosis infects more than 20%of the world population [1] and is the most frequent source of infection, especially in tropical countries [2, 3]. Compromised ability to retain a drug at the site of infection may lead to reduced efficacy and development of drug resistance [5, 9] This is evident from incidences of resistance to common drugs for treating dermatophytoses such as terbinafine, fluconazole, and griseofulvin [10,11,12]. Current topical anti-infective preparations are available in the form of ointments, creams, gels, lotions, and shampoo. These preparations have certain limitations like poor persistent contact with site of treatment, poor drug permeability, and compromised patient compliance due to them being messy, sticky, possessing an unattractive appearance, and interference with daily activities [14]

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