IN-VIVO CHARACTERIZATION OF TRANSDERMAL DRUG TRANSPORT BY MICRODIALYSIS

The aim of the present study was to evaluate the scope and limitations of the microdialysis technique as a tool for pharmacokinetic studies of transdermal therapy systems (TTS) and for characterization of the transdermal diffusion process in man. Nicotine (TTS; 21 mg/24 h) or est radiol (TTS; 100 mu g/24 h) were administered transdermally to 15 healthy volunteers. Microdialysis probes were inserted into defined skin layers directly underlying the TTS. Calibration of the probes was carried out in vitro and in vivo. The position of the probe and the depth of probe tip were established by 2D ultrasound scanning. Complete concentration versus time profiles could be obtained for nicotine. There was a high degree of association between the position of the microdialysis probe, measured in mm from the skin surface, and the area under the nicotine concentration versus time curve (AUG) or the steady state concentration in skin layers. Microdialysis measurements were reproducible for nicotine. Estradiol, which is poorly water soluble, was non-dialysable. Microdialysis sampling can provide previously inaccessible information about the transdermal diffusion process of select drugs and therefore represents a valuable addition to traditional attempts for characterization of the transdermal drug transport and of TTS release kinetics.