Iontophoretically enhanced ciclopirox delivery into and across human nail plate

Abstract

Transungual delivery of antifungal drugs is hindered by the low permeability of human nail plates, and as such, repeated dosing over a long period of time is necessary for effective treatment. The objectives of this study were to explore the possibilities of (a) enhancing the delivery of ciclopirox (CIC) across human nail plates and (b) sustaining CIC delivery from the larger resultant drug depot in the nail plates with constant voltage iontophoresis. In vitro passive and 9 V cathodal iontophoretic transport experiments of CIC across human nails were performed. Transungual CIC delivery with Penlac was the control. The amounts of CIC released from and deposited in the nails were determined in drug release and extraction experiments, respectively. Iontophoresis increased the flux of CIC permeated across the nail approximately 10 times compared to passive delivery from the same formulation or from Penlac. A significant amount of CIC was loaded into and released from the nails; the CIC concentrations were estimated to be above the minimum inhibitory concentrations of CIC for dermatophytic molds. The apparent transport lag time decreased in iontophoretic transport. The results demonstrate that iontophoresis was able to deliver an effective amount of CIC into and across the nails, and this suggests the feasibility of a constant voltage battery-powered transungual iontophoretic device.

Figure 1

Cumulative amounts of ciclopirox delivered across human nail plates at 9 h (Q₉) and 24 h (Q₂₄) in constant 9 V cathodal iontophoretic (dark bars), passive (gray bars), and Penlac® (open bars) transport experiments. Data represent the mean and standard deviation of 5-10 nail samples. The Q₂₄ data for passive transport are the average of the 24-h data in the 24- and 94-h passive transport experiments.

Figure 2

Fluxes (J) of ciclopirox across human nail plates in constant 9 V cathodal iontophoretic and 94-h passive transport experiments. Data represent the mean and standard deviation of 5-10 nail samples.

Figure 3

Total amounts of ciclopirox released from the nail plates at 24 and 50 h after 9 V cathodal iontophoretic (dark bars), 24-h passive (gray bars), and Penlac® (open bars) delivery. Data represent the mean and standard deviation of 5-10 nail samples.

Figure 4

Amounts of ciclopirox extracted from the nail plates after constant 9 V cathodal iontophoretic, 24-h passive, and Penlac® transport and subsequent release experiments. Data represent the mean and standard deviation of 5-10 nail samples.