Study of the Percutaneous Penetration of Flurbiprofen by Cutaneous and Subcutaneous Microdialysis after Iontophoretic Delivery in Rat

Abstract

The percutaneous penetration of flurbiprofen delivered by iontophoresis was investigated in the hairless rat. Unbound concentrations of flurbiprofen in dermis and subcutaneous tissue were continuously measured by on‐line microdialysis. Simultaneously, a conventional blood sampling was performed. Linear microdialysis probes were implanted in dermis and in subcutaneous tissue at a depth of 398.3 ± 15.3 and 1878 ± 35.8 μm, respectively. Commercial patches were used to deliver flurbiprofen for 15 min at a current density of 0.4 mA/cm2. In vivo recoveries of both probes, determined by using naproxen as retrodialysis calibrator, were 26.0 ± 0.3 and 72.9 ± 0.7% for dermal and subcutaneous probe, respectively. After iontophoretic delivery, a gradient in mean tissue unbound concentrations was observed, with a Cmax in dermis of 8.7 ± 0.4 μg/mL as compared with subcutaneous Cmax of 0.5 ± 0.1 μg/mL. The area under the unbound concentration curve in dermis was 13‐fold higher than that in the subcutaneous tissue. Total plasma concentration curves showed a rapid absorption phase with a Tmax of 30 min and Cmax of 1.8 ± 0.1 μg/mL. In conclusion, iontophoresis delivery was demonstrated to be efficient to deliver a high amount of flurbiprofen in dermis and underlying tissue with a fast input rate whereas maintaining a low plasma exposure.