A new formulation of topical efinaconazole allows the antifungal to penetrate through the nail plate much better than do existing treatments for onychomycosis, according to a report in the December issue of Journal of Drugs in Dermatology.
Poor nail penetration and diffusion through the thick, keratin-rich, lipid-containing barrier of the nail is the main factor limiting the effectiveness of current antifungals. A formulation with reduced keratin binding and lipophilicity would be more successful, particularly one with low surface tension to facilitate the transfer, wetting, spreading, and adhesion of the active ingredient under the surface of the nail, said Dr. Leon H. Kircik of Mount Sinai Medical Center, New York; Indiana University, Indianapolis; and Physician Skin Care PLLC, Louisville, Ky.
Dr. Kircik tested 41 possible liquid formulations of efinaconazole, assessed eight prototypes on nail samples from cadavers and in a guinea pig model, and settled on one formulation – (14C)-efinaconazole 10% topical solution – with the best penetrative and spreading properties to test in human subjects. This formulation contained ethanol as the primary vehicle and solvent, cyclomethicone as a wetting agent that reduces surface tension, esters to keep the efinaconazole in solution after the alcohol evaporates, preservatives, and water. When the solution is applied to the affected nail and the solvents evaporate, the concentration of the active ingredient increases to approximately 40%, Dr. Kircik noted.
Dr. Kircik then tested this formulation in 40 patients with toenail onychomycosis (mean age, 67 years), who applied it daily for 28 days and were followed for an additional 2 weeks. The concentrations of efinaconazole in the nail were 4 orders of magnitude higher than the MIC values of efinaconazole against dermatophytes. Drug concentrations were not affected by nail thickness or the severity of nail disease, and were maintained throughout follow-up. The findings indicate that after treatment is completed, “the nail plate and nail bed continue to be exposed to inhibitory drug concentrations for a period of time,” Dr. Kircik said (J. Drugs Dermatol. 2014;13:1457-61).
In 11 patients, Dr. Kircik assessed the ability of the active drug to reach the site of infection by spreading into the space between the nail plate and the nail bed, rather than directly through the nail plate. Fluorescein was incorporated into the topical preparation and applied distally between the nail and nail bed, without touching the surface of the toenail. Then visualization under UV light showed the spreading of the formulation to the nail bed, a finding that was confirmed after nail clipping.