Investigation into the potential of iontophoresis facilitated delivery of ketorolac

The potential for iontophoresis facilitated transdermal transport of ketorolac was investigated using rat skin. Studies of electrical, physicochemical and device-related factors acting on the permeation kinetics of in vitro iontophoresis were performed. Iontophoresis increased the transdermal permeation flux of ketorolac as compared to the diffusion. Increase in applied current density or decrease in ionic strength of the donor solution enhanced the flux of the drug. Use of either platinum or silver/silver chloride electrodes resulted in similar enhancement of drug flux. Continuous current was more potent than pulsed current in promoting ketorolac transdermal permeation. Increasing the frequency or on:off ratio of pulse current induced an enhancement of the flux through the skin. An increase in donor drug loading dose or increasing the duration of current application resulted in enhancement of the drug flux. Pretreatment of the skin with D-limonene in ethanol or D-limonene in ethanol+ultrasound significantly enhanced the iontophoretic flux of the drug in comparison to passive flux with or without pretreatment. Trimodality treatment comprising of pretreatment with D-limonene in ethanol+ultrasound in combination followed by iontophoresis was found to be most potent for enhancing the rate of permeation of ketorolac.