In vitro evaluation of poloxamer 407-based formulations for topical antifungal administration of terbinafine HCl and assessment of keratin film from human hair as a nail plate model

Abstract

Succeeding the previous work on poloxamer 407-based formulations as vehicles for 5-aminolevulinic acid (a hydrophilic active) this study focused on the incorporation of terbinafine hydrochloride (TBF), a lipophilic antifungal agent, and the physicochemical characterization thereof. The vehicle, which is known as thermogel, was composed of poloxamer 407, medium chain triglycerides, dimethyl isosorbide, isopropyl alcohol and water. TBF increased the gelation temperature of the vehicle and this was adjustable to meet the treatment need. TBF solubility varied depending on the composition of the vehicle, ranging from less than 2% to 4%. Stability study of selected formulations at 20 °C disclosed a larvated incompatibility between TBF and dimethyl isosorbide. The shelf life of the formulation was limited up to one month due to TBF degradation. TBF permeation from the selected formulations across human stratum corneum showed advantages over the other vehicles of comparison with respect to TBF fluxes and amounts retained in the stratum corneum. The permeation enhancement from the Thermogel was 1.4-fold, yet not statistically significant. However, the amount of TBF retained was significantly higher than that from Basiscreme DAC and Lamisil® Creme (1.3- and 2.2-fold, respectively). A higher flux of TBF was achieved by increasing TBF content in the formulation. In addition, a novel human nail model made of human hair keratin was developed to compensate for the restrictions of bovine hoof as the existing nail model. Despite its low hydration capability, this so-called keratin film (KF) was a promising nail plate model for testing hydrophilic substances. KF was further employed in an in vitro efficacy test of the formulations containing TBF. The result revealed that TBF diffusion from the formulation across KF was able to inhibit the growth of Trichophyton rubrum, the main causative agent of mycosis.