An In-Vitro Iontophoretic Permeation Study of Nicotine through Rat Skin

Nicotine transdermal systems are being used as an aid to smoking cessation programs. As the kinetics of nicotine delivery is important in success of a smoking cessation program, rapid and high input of nicotine is required, which is not possible by passive methods and requires enhancement strategies such as iontophoresis. Iontophoretic permeation, of nicotine looks promising, based on published data on human skin. However, to optimize this method, permeation pathways should be known and further parameters have to studied, which are the subject of the present investigation. In this study iontophoretic permeation of nicotine through rat skin was performed and the effects of different variables on this phenomenon were studied. Anodic iontophoresis of nicotine from a solution at pH 2.8, using a 0.5 mA/cm² current density resulted in a considerable enhancement (about 3-fold) of nicotine absorption through rat skin. Nicotine concentration and current density showed a directly increasing effect on permeation of the drug, but the effect of concentration was not linear. Pulsatile current delivery was more effective in permeation of nicotine than the continuous method. Anodic iontophoresis was around 2-fold more effective than the cathodic method in increasing the flux. Post iontophoretic permeation studies showed good reversibility of the membrane barrier properties. Results were in good agreement with the reported human data and might be considered as an evidence of the ability of rat skin to model human skin and also the importance of intercellular pathway of the stratum corneum in iontophoretic delivery of nicotine and possibly other drugs. Donor's pH showed no effect on permeation of nicotine under the studied conditions, pH values of <3. Results also showed that the electr-osmotic flow could occur at pH values lower than 4. Finally, this study show that by controlling the effective parameters of iontophoretic delivery, a more effective nicotine transdermal delivery method would achievable.