Ungual and trans-ungual iontophoretic delivery of terbinafine for the treatment of onychomycosis

• Published in: Journal of pharmaceutical sciences 2009-11, Vol.98 (11), p.4130-4140
• Main Authors: Nair, Anroop B., Kim, Hyun D., Chakraborty, Bireswar, Singh, Jagpal, Zaman, Muhammad, Gupta, Aditya, Friden, Phillip M., Murthy, S. Narasimha
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antifungal Agents - administration & dosage; Antifungal Agents - analysis; Antifungal Agents - chemistry; Antifungal Agents - pharmacokinetics; binding; Cadaver; Chromatography, High Pressure Liquid; Drug Delivery Systems; drug-release; Female; Humans; Hydrogen-Ion Concentration; Iontophoresis; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Weight; nail; Nails - metabolism; Naphthalenes - administration & dosage; Naphthalenes - analysis; Naphthalenes - chemistry; Naphthalenes - pharmacokinetics; onychomycosis; Onychomycosis - drug therapy; Onychomycosis - microbiology; Permeability; Rhodospirillum rubrum - drug effects; terbinafine; Time Factors
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1002/jps.21711

The application of iontophoresis was demonstrated in the nail drug delivery of terbinafine (TH) recently. This study explored a systematic assessment of this approach to enhance the drug delivery using a novel topical formulation, and the subsequent release of TH from the drug loaded nails. For the first time, a nail on-agar plate model was used to study the release of drug from the iontophoresis (0.5 mA/cm2) loaded nails. In addition, the activity of the drug released from the drug loaded nail plate was studied against Trichophyton rubrum. An increase in applied current density and current duration enhanced the transport of TH into and through the nail plate. In vitro release of drug from the iontophoretic loaded nails into agar plates exhibited 2-phase release pattern. The amount of drug released in both of the in vitro models was comparable, and the nails loaded using iontophoresis continued to release levels of TH>2 orders of magnitude above the minimum inhibitory concentration over at least 52 days. Results indicate that iontophoresis enhances the delivery of terbinafine into and through the nail plate and suggest that the use of this treatment approach could result in a safe and more efficacious outcome with less frequent treatments. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4130–4140, 2009