It should be noted that the voltage conditions (0.5 and
2.5 V) used in the present study cover the voltage range
commonly encountered in transdermal iontophoretic transport
in human in practice: the applied voltage across skin
ranges from 0.4 V to 3 V when the skin electrical resistance is
4 to 10 kWcm2 under the current density of 0.1 or 0.3 mA/cm2
.
The fully hydrated SC condition is also likely to be encountered
in vivo under prolonged skin exposure to a transdermal
iontophoresis electrode. Under these conditions, very low
frequency is required to provide the maximum flux
enhancement in AC transdermal iontophoresis. AC flux
enhancement reaches the maximum value (of one-half of the
DC flux enhancement) at 0.001 Hz under the applied electric
fields examined in the present study. This is consistent with
previous AC studies conducted at AC frequency much higher
than this maximum region showing significantly larger DC flux
enhancement than that of AC (5). To put this observation into a
practical perspective, maximum AC flux enhancement is
achieved at frequency at or below 0.001 Hz, this
corresponding to 8.3 min of DC in each direction in an AC
cycle. The AC frequencies used in the commercial AC
transdermal iontophoresis devices such as the Lectro Patch
(General Medical Co., CA), GlucoWatch G2i Biographer
(Cygnus Inc., CA) are barely in this frequency range. The low
frequency required to reach the maximum AC flux enhancement
is unexpected as one would predict that the thin SC would
require less than 1 min to achieve full iontophoresis enhancement
effect in transdermal transport. This illustrates the importance of
understanding the AC flux enhancement-AC frequency
relationships to provide information for future development of
AC iontophoretic delivery so that the enhancement effects of
electrophoresis and electroosmosis in transdermal iontophoretic
transport involving alternating polarity can be optimized. Future
studies are required to determine the AC flux vs AC frequency
relationships under different conditions such as in phosphate
buffered saline (vs in TEAP) for iontophoretic extraction and in
drug solutions for delivery