Influence of human nail etching for the assessment of topical onychomycosis therapies.

The purpose of this investigation was to study the physico-chemical properties of hot-melt extruded films containing ketoconazole and to determine the influence of 'nail etching' on film bioadhesion and drug permeability for the assessment of topical onychomycosis therapies. Hot-melt extrusion (HME) was used to prepare films containing 20% w/w ketoconazole. Ketoconazole 0.125% gel was also prepared using Carbopol 974P NF. Films were processed at a temperature range of 115-120 degrees C utilizing a Killion extruder (KLB-100), and were evaluated for post-extrusion drug content, content uniformity, bioadhesion, thermal behavior and nail drug permeation. The extruded films demonstrated excellent content uniformity and post-processing drug content. Tensile and peel tests were recorded to determine the bioadhesive profiles. In this study, work of adhesion and peak adhesive force determinations using the peel tests provided more sensitive results for evaluating the bioadhesivity of the HME films than the tensile tests. The in vitro permeability profiles have demonstrated, that nail samples treated with an 'etchant' demonstrated a significant increase in drug permeability compared to control. Differential scanning calorimetry (DSC) thermograms indicated that ketoconazole was in solid solution within the HME films. These findings are encouraging for the future design and formulation of novel drug delivery systems for the topical treatment of onychomycosis.