CURRENT PROFILE REGULATES IONTOPHORETIC DELIVERY OF AMINO-ACIDS ACROSS THE SKIN

In most of the reported studies of iontophoresis, direct current (DC), continuously applied for a defined period, has been used. However, th is current profile can result in skin polarization and irritation. The refore, the impact of alternative current profiles in regulating the p ermeation of two charged amino acids, lysine and glutamic acid, has be en studied. The current profiles considered were: (1) none (passive co ntrol); (2) DC; (3) square-wave alternating current (AC) with differen t bipolar duty cycles (i.e., + / - ratios); (4) sine-wave AC; and (5) pulsed DC with different on/off ratios. Drug flux (nmol/cm(2) per h), cumulative drug permeation (%), and amount of the drug in the skin aft er iontophoresis were determined in vitro using hairless mouse skin. T he principal findings were: (1) Iontophoretic transport can be signifi cantly modified and regulated by the use of different current profiles . (2) In terms of total transmembrane drug delivery, constant DC is mo st efficient; pulsed DC, even at comparable charge, may not deliver as much drug as uninterrupted DC. (3) Square-wave and sine-wave AC profi les (again, at comparable total charge) result in comparable transport rates. (4) Lysine and glutamic acid fluxes are directly proportional to the unipolar square-wave (positive) duty cycle; with bipolar AC (po sitive and negative), measurable drug delivery requires a threshold of 50% positive duty cycle, whereafter amino acid delivery is linear to 100%. (5) The frequency (2.5-2500 Hz) does not significantly effect th e delivery of these small molecules. Pulsed iontophoresis, bipolar or unipolar, may be used as an effective and, potentially, better tolerat ed means of transdermal drug delivery relative to constant DC. The ion tophoretic delivery of charged species can be controlled over a wide r ange, therefore, by appropriate regulation of the current profile and/ or duty cycle.