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  • Title: Study of the percutaneous penetration of flurbiprofen by cutaneous and subcutaneous microdialysis after iontophoretic delivery in rat.
    Author: Mathy FX, Lombry C, Verbeeck RK, Préat V.
    Journal: J Pharm Sci; 2005 Jan; 94(1):144-52. PubMed ID: 15761938.
    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 microm, respectively. Commercial patches were used to deliver flurbiprofen for 15 min at a current density of 0.4 mA/cm(2). 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 C(max) in dermis of 8.7 +/- 0.4 microg/mL as compared with subcutaneous C(max) of 0.5 +/- 0.1 microg/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 T(max) of 30 min and C(max) of 1.8 +/- 0.1 microg/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.
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