Enhanced terbinafine topical delivery to the nail by new formulation-microporation approaches

Effective topical antifungal nail delivery is challenged by the actives' poor permeation across the nail plate, a thick, hard keratin, structure. This work investigated whether terbinafine ungual delivery could be improved by combining physical enhancement approaches, nail microporation and microchanneling, with new terbinafine vehicles. The new microemulsion-, liquid crystal- and thermogel- based formulations contained 2-7 % of the active, enabling higher active loads than current commercial 1 % topical products. In vitro release and permeation studies were performed using artificial membranes and healthy human nails, respectively. In vitro permeation studies demonstrated that microporation and nail microchanneling resulted in greater drug uptake into the nail and delivery to the receptor, despite the application of smaller doses of drug throughout the study. Best results were obtained with microemulsions, particularly ME5, containing 7 % of the drug. Additionally, microbiological tests performed to evaluate the antifungal activity of the formulations against T. rubrum and C. parapsilosis confirmed the superiority of the ME5 7 %. On the whole, the results reported here support the development of new nail drug delivery systems combined with physical permeation enhancers.