An optimization strategy for enhancing iontophoretic transdermal drug delivery: Skin impedance and iontophoretic waveform parameter analysis

An optimization strategy to increase the effectiveness of iontophoretic delivery has been developed. In particular, those parameters relating to mammalian skin impedance and the electrical driving parameters used during iontophoresis were analyzed. Several of the available electrical analog models of mammalian skin impedance were reviewed and analyzed using PSPICE simulations to determine their effects on stratum corneum (SC) capacitance, deep tissue current, and delivery efficiency. Typical and atypical iontophoretic electrical driving waveforms were analyzed using frequency spectrum analysis to determine which electrical driving signals provided the greatest drug delivery or deep tissue current. The electrical waveform parameters analyzed were frequency, duty cycle, amplitude, mode (current or voltage) and morphology. Results from the simulations provided valuable insight which helped predict the results of in vitro experiments. Consequently, simulations could only vary one parameter at a time; therefore, design of experiments (DOE) techniques were used in the in vitro experiments to analyze interactions between waveform parameters. NaCl was used as the sample drug of choice and porcine skin was used for all in vitro experiments. Furthermore a Variable Frequency Skin Impedance Monitor (VFSIM) device was developed to automatically collect skin impedance spectrums of various samples.; In vitro experiments showed that the two most important parameters affecting drug delivery were amplitude and the combination of amplitude and duty cycle. Duty cycle alone was found to be borderline significant. Although DOE results showed that duty cycle was proportional to drug delivery, separate experiments using iontophoretic waveforms of equal area but varying duty cycle showed significantly more drug delivery for the smaller duration duty cycle.; Any optimization scheme for iontophoretic delivery should involve; trapezoidal voltage pulses, impedance monitoring, short-duration high-amplitude pulses, and proper stimulating frequency selection.