TRANSDERMAL IONTOPHORESIS OF SOTALOL AND SALICYLATE - THE EFFECT OF SKIN CHARGE AND PENETRATION ENHANCERS

Transdermal iontophoresis of sotalol was studied in horizontal diffusi on chambers in the presence and absence of penetration enhancers dodec yl N,N-dimethyl amino acetate (DDAA) and Azone using the constant pote ntial drop of 0.5 V across human cadaver skin, and the results were co mpared with the ones of shed snake skin, Elaphe obsoleta. DDAA and Azo ne improved the permeation of sotalol in human cadaver skin equally to that of iontophoresis with 0.5 V potential drop, i.e., 6-13-fold in c omparison to the control without enhancement. Combination of iontophor esis and penetration enhancers did not further increase the permeation ; in fact, the combination seemed to decrease it slightly when compare d to iontophoresis or enhancers alone. The effect of skin charge on th e transport was studied comparing the permeabilities of cationic sotal ol and anionic salicylate in human and snake skin which have different ion selective properties. Sotalol appeared to penetrate better throug h human skin while salicylate penetrated better through snake skin. Th e principal route of charged drugs during iontophoresis is proposed to be through the skin appendages while neutral solutes are transported through the lipid matrix of skin. The permeation of tritiated water in creased slightly during iontophoresis and in a more pronounced manner in the presence of DDAA and Azone.