A pilot, layerwise, ex vivo evaluation of the antifungal efficacy of amorolfine 5% nail lacquer vs other topical antifungal nail formulations in healthy toenails

Abstract

Summary Background Studies investigating the penetration of amorolfine through the nail have shown the highest concentration in the uppermost layer and measurable antifungal activity even in the lower layers of the nail. Objectives This pilot, ex vivo study compared the penetration of antifungal concentrations of amorolfine 5% nail lacquer in different layers of healthy, human cadaver toenails with that of terbinafine 10% nail solution, ciclopirox 8% nail lacquer and naftifine 1% nail solution. Moreover, the effect of nail filing prior to application on the penetration of amorolfine 5% was assessed. Methods Unfiled (n = 3) and filed (n = 3) nails were used for each antimycotic agent and amorolfine 5% nail lacquer, respectively. Twenty‐four hours after topical application, the nails were sliced (10 μm), solubilised and added to agar plates seeded with Trichophyton rubrum. Zones of growth inhibition were measured. Results Only amorolfine penetrated the nails at sufficient concentrations to inhibit growth of T rubrum at different nail depths. In contrast, the comparators did not show antifungal efficacy. Nail filing resulted in larger zones of inhibition for amorolfine compared with those of intact nails. Conclusions Unlike its comparators, a single application of amorolfine 5% nail lacquer resulted in antifungal efficacy within the nail plate. Nail filing increased the antifungal efficacy of amorolfine 5% nail lacquer.

Visualisation of penetration of topical antifungal drug substances through mycosis‐infected nails by matrix‐assisted laser desorption ionisation mass spectrometry imaging

“…After 24 hours, a significant fraction of this active substance is also present in the lower layers of the nail plate (Figure 2A,B, first row). These results confirm previous findings of Ghannoum et al, 12 which showed higher antifungal growth inhibition for amorolfine in deeper layers of the nail within 24 hours of a single application compared to ciclopirox 8% nail lacquer, naftifine hydrochloride 1% solution and terbinafine hydrochloride 10% nail solution. 12 Amorolfine has low affinity for keratin compared with ciclopirox 23 and naftifine, 24 which may contribute to a high concentration of free drug and permeation to the deeper layers of the nail.…”

“…27,28 In this study, ciclopirox and amorolfine were applied on the nails as nail lacquers, and this could explain the superior penetration results observed for these two drugs compared to naftifine solution. When comparing the distribution profile of the three drugs evaluated, amorolfine showed a better penetration than the other two molecules, and the filing of the nails (according to regulatory approval status) could have contributed to the enhanced amorolfine penetration as claimed by Ghannoum et al 12 The ciclopirox and naftifine hydrochloride containing topical preparations (Ciclopoli ® /Exoderil ® ) are water-soluble topical formulations, which can accidentally easily be washed off from the nail plate by patients during routine use. Therefore, a remanence period of 24 hours after a topical application of these galenical formulations on the nail surface is practically unlikely in daily clinical practice.…”

“…Numerous parameters can interfere in the drug penetration through the fungal infected nail plate, such as hydration and thickness of the nails, physico‐chemical properties of the pharmaceutical compound, the formulation and the binding of the drug to the nail matrix 10 . Antifungal nail lacquers, such as Loceryl ® and Ciclopoli ® used in this study, have been described to be the most suitable topical formulation to treat onychomycosis, 11 providing longer permanence of the formulation to the nail, which allows continuous release of the active agent, enhancing the penetration of the drug 12 . Topical antifungal solutions are also available, such as naftifine hydrochloride 1%, which can be effectively used against a broad spectrum of dermatophyte fungi of Trichophyton spp, which includes the Trichophyton rubrum , that can cause onychomycosis infections 13,14 …”

“…10 Antifungal nail lacquers, such as Loceryl ® and Ciclopoli ® used in this study, have been described to be the most suitable topical formulation to treat onychomycosis, 11 providing longer permanence of the formulation to the nail, which allows continuous release of the active agent, enhancing the penetration of the drug. 12 Topical antifungal solutions are also available, such as naftifine hydrochloride 1%, which can be effectively used against a broad spectrum of dermatophyte fungi of Trichophyton spp, which includes the Trichophyton rubrum, that can cause onychomycosis infections. 13,14 Molecular penetration of compounds into infected human nail plate has been investigated with the use of different approaches.…”

Kombinationstherapie von schweren Onychomykosen – Empfehlungen eines Expertengremiums

“…B. durch Abfräsen der Nagelplatte. Vor der Anwendung von Antimykotika sollte die Nageloberfläche jeweils durch Fräsen oder Feilen aufgeraut werden, um das obere Drittel der Nagelplatte als anatomische Penetrationsbarriere auszudünnen und ein effektives Eindringen der Antimykotika in das gesamte Nagelmaterial zu begünstigen [1]. Dies gilt insbesondere bei dicken Nägeln (≥ 2 mm) und bei Nägeln mit Dermatophytom (Gletschernagel).…”