Transdermal delivery of metoprolol by electroporation.
Electroporation, i.e., the creation of transient "pores" in lipid membranes leading to increased permeability, could be used to promote transdermal drug delivery. We have evaluated metoprolol permeation through full thickness hairless rat skin in vitro following electroporation with an exponentially decaying pulse. Application of electric pulses increased metoprolol permeation as compared to diffusion through untreated skin. Raising the number of twin pulses (300 V, 3 ms; followed after 1 s by 100 V, 620 ms) from 1 to 20 increased drug transport. Single pulse (100 V, 620 ms) was as effective as twin pulse application (2200 V, 1100 V or 300 V, 3 ms; followed after 1 s by 100 V, 620 ms). In order to investigate the effect of pulse voltage on metoprolol permeation, 5 single pulses (each separated by 1 min) were applied at varying voltages from 24 to 450 V (pulse time 620 ms). A linear correlation between pulse voltage and cumulative metoprolol transported after 4 h suggested that voltage controls the quantity of drug delivered. Then, the effect of pulse time on metoprolol permeation was studied by varying pulse duration of 5 single 100 V pulses from 80 to 710 ms (each pulse also separated by 1 min). Cumulative metoprolol transported after 4 h increased linearly with the pulse time. Therefore, pulse time was also a control factor of the quantity of drug delivered but to a lesser extent than the voltage at least at 100 V.(ABSTRACT TRUNCATED AT 250 WORDS)
Vanbever
R
R
Université Catholique de Louvain, Unité de Pharmacie Galénique, Brussels, Belgium.
Lecouturier
N
N
Préat
V
V
D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems; D004558:Electric Stimulation; D018274:Electroporation; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D051381:Rats
D008790:Metoprolol