Ciclopirox vs Amorolfine: In Vitro Penetration Into and Permeation Through Human Healthy Nails of Commercial Nail Lacquers

February 2014 | Volume 13 | Issue 2 | Original Article | 143 | Copyright © 2014

Daniela Monti PhD,a Silvia Tampucci PhD,a Patrizia Chetoni PhD,a Susi Burgalassi PhD,a and Federico Mailland MDb

aDepartment of Pharmacy, University of Pisa, Pisa, Italy
bScientific Department, Polichem SA, Lugano, Switzerland

Abstract

One of the pre-requisite for a successful topical antifungal drug indicated for onychomycosis is its bioavailability into the nail unit for achieving fungal eradication and clinical benefit. The aim of this study was to compare in vitro permeation/penetration through and into human nails of amorolfine (MRF) from a 5% anhydrous commercial formulation (Loceryl®) and ciclopirox (CPX) from the 8% aqueous formulation in hydroxypropyl chitosan (HPCH) technology (Onytec®). The ability of the active ingredient to reach efficacious concentrations to inhibit nail pathogens was also evaluated. The amounts of drug permeated and retained in human healthy nails were determined using a suitably modified diffusion apparatus. HPLC analysis of the samples was performed. The HPCH-based CPX formulation demonstrated an efficient penetration into and permeation through the nail plates. Conversely, Loceryl® produced an amount of MRF permeated through and penetrated into the human toenails significantly lower than CPX. The evaluation of the efficacy index showed a higher potential efficacy of Onytec® with respect to Loceryl® on nail pathogens. The present work not only reinforced the previous results on different experimental substrates, but pointed out the superiority of HPCH-based Onytec® formulation containing CPX with respect to Loceryl® commercial product with MRF, both in terms of higher permeation through and penetration into the human nail, and for the efficacy towards the most common ungual pathogens.

J Drugs Dermatol. 2014;13(2):143-147.

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INTRODUCTION

Onychomycosis is a nail disease, which affects a high percentage of adult population and presents many difficulties in treatment management.1-3 The therapy consists mainly in broad-spectrum antimycotic agents administered via the systemic or topical route, but the efficacy of the treatment is impaired by the difficulty to reach and maintain effective drug levels at the site of infection.2,4 Moreover, since failures and relapses are quite frequent5,6 and the pathology doesn’t undergo spontaneous remission, prolonged treatments are necessary, with the consequence of possible adverse reactions and drug interactions in case of systemic therapy.7,8 Topical therapy could represent a valid alternative; in particular current strategies include topical nail lacquers, able to promote the drug permanence at the site of action.6,9-11 The only antifungal agents commercialized in Europe as nail lacquers are ciclopirox and amorolfine, extensively investigated in recent years in order to establish their effectiveness in the treatment of onychomycosis. 8,12-14 While amorolfine is commercialized only in a lacquer formulation containing water insoluble polymer (Loceryl®, Curanail®), ciclopirox is present on the market both in anhydrous (Penlac®, Batrafen®, Mycoster®) and aqueous-based nail lacquer containing hydroxypropyl chitosan (HPCH) as a filmforming agent (Onytec®, Ciclopoli®). Monti et al.15 demonstrated the higher efficacy of this formulation with respect to old generation lacquer (Penlac) in promoting in vitro ciclopirox penetration through bovine hoof slices. Moreover, a multicenter randomized study from Baran et al.16 highlighted the superiority of ciclopirox in the HPCH technology when compared to Penlac® in terms of keratin affinity and nail permeation11. The superior transungual permeation and antimycotic activity of ciclopirox in the HPCH technology with respect to amorolfine was demonstrated as well, in both in vitro and in vivo studies.17,18 But, while the performance of the new vehicle with ciclopirox has been tested in vitro on bovine hoof slices and human nails19 no study was performed on human substrates for amorolfine until now.

Therefore, aim of the present investigation was the evaluation of permeation and distribution of amorolfine (MRF) and ciclopirox (CPX) through human healthy nails after application of commercial products Loceryl® (5% MRF) and Onytec® (8% CPX), respectively.

MATERIAL AND METHODS

Chemicals

The following products were used as received: amorolfine (Polichem SA, Switzerland); ciclopirox (CPX, Erregierre SpA, Italy); Loceryl® (batch 021273, Galderma International, France); Onytec® (batch 8026A, Laboratoires Bailleul-Biorga, France). All other chemicals and solvents were of analytical grade.

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