Preparation, Characterisation, and Topical Delivery of Terbinafine.

A S M Monjur Al Hossain,Rebecca Lever,Jonathan Hadgraft,Fotis Iliopoulos,Bruno C Sil,Majella E Lane

doi:10.3390/pharmaceutics11100548

A S M Monjur Al Hossain, Rebecca Lever + Show 4 more

Open Access

https://doi.org/10.3390/pharmaceutics11100548

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Abstract

Terbinafine (TBF) is commonly used in the management of fungal infections of the skin because of its broad spectrum of activity. Currently, formulations containing the free base and salt form are available. However, there is only limited information in the literature about the physicochemical properties of this drug and its uptake by the skin. In this work, we conducted a comprehensive characterisation of TBF, and we also examined its percutaneous absorption in vitro in porcine skin. TBF-free base was synthesised from the hydrochloride salt by a simple proton displacement reaction. Both the free base and salt form were further analysed using Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Delivery of TBF-free base in excised porcine skin was investigated from the following solvents: Isopropyl myristate (IPM), propylene glycol monolaurate (PGML), Transcutol® (TC), propylene glycol (PG), polyethylene glycol 200 (PEG 200), oleic acid (OL), ethanol (EtOH), and isopropyl alcohol (IPA). Permeation and mass balance studies confirmed that PG and TC were the most efficacious vehicles, delivering higher amounts of TBF-free base to the skin compared with a commercial gel (p < 0.05). These preliminary results are promising and will inform the development of more complex formulations in future work.

Highlights

Fungal skin infections are reported to be the most common skin disease, and were ranked in the top 10 most prevalent diseases worldwide in 2010 [1,2,3,4]
The objectives of the present work were to (1) characterise the relevant physical and chemical properties of TBF-free base for topical delivery, and (2) examine the delivery of TBF-free base from simple solvents compared with a commercial control
Trifluoroacetic acid was supplied by Acros Organics (Fisher Scientific, Leicestershire, UK) and oleic acid (OL) from Fluka (Sigma-Aldrich, Dorset, UK)

Summary

Introduction

Fungal skin infections are reported to be the most common skin disease, and were ranked in the top 10 most prevalent diseases worldwide in 2010 [1,2,3,4]. About 25% of the world’s population has been reported to have fungal infections of the skin or nails of the foot [2,5]. These infections are often seen in the outer layers of the skin, the nails, and hair [3]. The skin between the toes is more prone to fungal infection (athlete’s foot) and inflammation and itchiness are pervasive problems in this case [7]. There is no consensus with regard to the optimal period of treatment, drug dose, and frequency of application of topical preparations of antifungal agents [8]

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