Rm. Brand et Rh. Guy, IONTOPHORESIS OF NICOTINE IN-VITRO - PULSATILE DRUG-DELIVERY ACROSS THE SKIN, Journal of controlled release, 33(2), 1995, pp. 285-292
Transdermal delivery systems containing nicotine are now being used as
aids in smoking cessation programs. This route of administration resu
lts in blood nicotine levels which increase gradually with time before
reaching maximal levels and then slowly tapering off. Typically, howe
ver, 3-4 h are required before an amount of nicotine, equivalent to th
at delivered by a single cigarette, is absorbed transdermally. If one
accepts that the kinetics of nicotine delivery are important to the li
kely success of a smoking cessation program, one is led to the hypothe
sis that the input process of the drug should be more rapid than that
presently achieved by the approved transdermal systems. Here, we repor
t on an attempt to accelerate nicotine absorption using iontophoresis.
Anodal delivery of nicotine from a solution at pH 7.4 using reasonabl
e current densities resulted in considerable enhancement of nicotine t
ransport in vitro across hairless mouse skin. Extrapolation of this re
sult to a 30-cm(2) patch implies that a 'cigarette's worth' (similar t
o 1 mg) of drug could be delivered within 30 min. At least 10 min of c
ontinuous current passage at 0.5 mA/cm(2) 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 cont
rolled the initial rate of drug delivery. Iontophoretic delivery appea
red optimal at neutral pH. There was a nonlinear relationship associat
ed 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.