Development of a transdermal sumatriptan formulation with iontophoresis

Objective A transdermal iontophoretic formulation for sumatriptan was approved by the U.S. FDA in 2013 for patients who cannot take oral medications. However, it was withdrawn in 2020 due to skin burns and scarring associated with prolonged electrical applications. This study aimed to determine whether short-duration, low-current iontophoresis can still achieve therapeutically effective plasma concentrations of sumatriptan.Significance: Developing a safe, rapid-acting transdermal delivery system would provide an alternative treatment option for patients who cannot tolerate oral medications, while reducing the risk injury caused by long-term electrical exposure.Methods The target plasma concentration in rats was calculated from rat elimination pharmacokinetics and previously reported human therapeutic concentrations. Rats received 0.04, 0.2, or 0.4% sumatriptan gel on the abdominal skin, and iontophoresis was applied at 0.05, 0.1, or 0.2 mA/cm2 for 2 h. Plasma concentrations were measured over time. An additional experiment applied 0.2 mA/cm2 for 0.5 h followed by 0.1 mA/cm2 for 0.5 h.Results Based on the maximal plasma concentration after oral administration in humans (16.5 ng/mL), the target plasma concentration in rats was calculated as 0.94 μg/mL. The 0.2 and 0.4% formulations at 0.1 mA/cm2 exceeded this target within 1.5 and 1.0 h, respectively. The 0.2% formulation at 0.2 mA/cm2 surpassed the target within 0.5 h and maintained it for 3 h.Conclusions Short-duration, low-current iontophoresis effectively achieved therapeutic plasma concentration of sumatriptan. These findings support the potential of this approach as a safer transdermal alternative for patients unable to take oral medications.