Vanbever-R; Morre-ND; Preat-V
Pharm-Res. 1996 Sep; 13(9): 1360-6
PURPOSE: The aim of the present report was to systematically analyze
the mechanisms involved in fentanyl transdermal transport by skin electroporation.
METHODS: The study was performed in vitro with full-thickness hairless
rat skin, skin electroporation being carried out with five exponentially-decaying
pulses of 100 V applied voltage and around 600 ms pulse duration.
RESULTS: Transport during and after pulsing are both important in transdermal
delivery of fentanyl by skin electroporation. Rapid transport occurred
during pulsing due to electrophoresis and diffusion through highly permeabilized
skin. No electroosmosis was observed. The slow post-pulse passive transport
was explained by lasting changes in skin permeability. Measurements of
fentanyl quantities in the skin demonstrated that pulses rapidly loaded
the viable part of the skin with fentanyl and hence rapidly overcame skin
barrier.
CONCLUSIONS: The different contributions of the transport mechanisms
appear to depend on the physicochemical parameters of the transported molecule
as well as the solution, suggesting that mechanistic analysis and careful
consideration of formulation variables are essential for the development
and optimization of drug delivery by skin electroporation.