Iontophoresis of nicotine in vitro: pulsatile drug delivery across the skin?

Transdermal delivery systems containing nicotine are now being used as aids in smoking cessation programs. This route of administration results in blood nicotine levels which increase gradually with time before reaching maximal levels and then slowly tapering off. Typically, however, 3-4 h are required before an amount of nicotine, equivalent to that delivered by a single cigarette, is absorbed transdermally. If one accepts that the kinetics of nicotine delivery are important to the likely success of a smoking cessation program, one is led to the hypothesis that the input process of the drug should be more rapid than that presently achieved by the approved transdermal systems. Here, we report on an attempt to accelerate nicotine absorption using iontophoresis. Anodal delivery of nicotine from a solution at pH 7.4 using reasonable current densities resulted in considerable enhancement of nicotine transport in vitro across hairless mouse skin. Extrapolation of this result to a 30-cm² patch implies that a 'cigarette's worth' ( ∼ 1 mg) of drug could be delivered within 30 min. At least 10 min of continuous current passage at 0.5 mA/cm² was required to produce this rate of delivery. The total charge delivered determined the amount of nicotine crossing the skin, whereas the amplitude of the current controlled the initial rate of drug delivery. Iontophoretic delivery appeared optimal at neutral pH. There was a nonlinear relationship associated with donor nicotine concentration. Decreasing the competitor sodium ions improved the amount of nicotine delivered, whereas substituting less mobile calcium ions did not. It follows that, by controlling the parameters of a putative iontophoretic nicotine formulation, rapid and pulsatile transdermal drug delivery may be achievable.