ARTICLE AUTHOR: Vanbever-R; Preat-V

REPRINT AUTHOR: Preat, V; UNIV CATHOLIQUE LOUVAIN; UNITE PHARM GALEN IND AND OFFICINALE, AVE E MOURNIER, 73 UCL 7320; B-1200 BRUSSELS; BELGIUM

SOURCE: BIOELECTROCHEMISTRY-AND-BIOENERGETICS. AUG 1995; 38 (1) : 223-228

ABSTRACT:

Electroporation, i.e. the creation of transient enhanced lipid membrane permeability using high intensity electric field pulses, can be used to promote transdermal drug delivery. Compared with diffusion through untreated skin, the application of electrical pulses allows us to obtain an up to 1000-fold increase in the quantities of metoprolol transported through the skin in an in vitro model. The present study shows that, as the voltage of five pulses of 620 ms increased from 24 to 250 V, the quantities of metoprolol permeating through the skin increased approximately in proportion to the square of the voltage. From 74 to 250 V, these quantities increased linearly with the voltage. The threshold of the voltage necessary to detect some increase in metoprolol permeation was around 24 V for these electrical conditions. As the pulse duration of five single pulses of 100 V varied from 80 to 700 ms, the quantities of metoprolol transported increased linearly. The threshold of the pulse time was approximately 80 ms for these electric conditions. The combination of these results indicated that the quantities of metoprolol that permeated through the skin was in direct proportion to the electrical energy of the pulses. The twin pulse appeared to be interesting to enhance metoprolol permeation only when the second pulse had a voltage of 24 V. The application of a low number of low voltage - long duration pulses was more efficient than the application of a high number of high voltage - short duration pulses to promote transdermal permeation of metoprolol by electroporation. These results suggest that the threshold voltage and threshold duration of the pulse are critical for transdermal permeation. As for cells, electropermeabilization of the skin could be a two-steps process: one step of the induction of a transient permeated structure and another a step of the maintenance or expansion of these structures and/or electrophoretic movement.