- The objective of this study was to demonstrate the potential of the application of a short-term iontophoresis on the topical delivery of lidocaine hydrochloride from a microemulsion-based system. Five- and 10-min durations of anodal iontophoresis applied onto porcine skin were examined in combination with a microemulsion containing 2.5% lidocaine hydrochloride. A similar combination (10-min iontophoresis with microemulsion in the anodal electrode) was also examined in vivo in a rat model. It was shown in vitro that by combining microemulsion application with a 10-min iontophoresis of 1.13 mA/cm 2 electric current density, a significantly increased flux was obtained compared with a combination of aqueous drug solution with the same iontophoresis protocol. In vivo studies revealed that 57.71 ± 18.65 and 18.43 ± 9.17 μg cm −2 were reached in the epidermis and dermis, respectively, at t = 30 min of microemulsion application, when iontophoresis was applied for 10 min. In contrast, the application of aqueous solution-iontophoresis resulted in a relatively lower drug accumulation (21.44 ± 10.42 and 5.30 ± 2.25 μg cm −2 in the epidermis and dermis, respectively, at t = 30) with more rapid clearance of the drug from the skin. Ten-minute application of a low-current electric field on a new topical microemulsion appears to make significant changes in skin permeability. The potential advantages of this procedure include significantly increased flux, accumulation of a large skin drug depot, short lag times, reduced irritation (compared to long-term iontophoresis), simplicity and ease of compliance.