Transdermal iontophoresis of sotalol and salicylate; The effect of skin charge and penetration enhancers
Hirvonen, J.; Kontturi, K.; Murtomaki, L.; Paronen, P.; Urtti, A.
Journal of Controlled Release 26(2): 109-117
Transdermal iontophoresis of sotalol was studied in horizontal diffusion chambers in the presence and absence of penetration enhancers dodecyl N,N-dimethyl amino acetate (DDAA) and Azone using the constant potential drop of 0.5 V across human cadaver skin, and the results were compared with the ones of shed snake skin, Elaphe obsoleta. DDAA and Azone 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 comparison to the control without enhancement. Combination of iontophoresis and penetration enhancers did not further increase the permeation; in fact, the combination seemed to decrease it slightly when compared to iontophoresis or enhancers alone. The effect of skin charge on the transport was studied comparing the permeabilities of cationic sotalol and anionic salicylate in human and snake skin which have different ion selective properties. Sotalol appeared to penetrate better through human skin while salicylate penetrated better through snake skin. The 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 increased slightly during iontophoresis and in a more pronounced manner in the presence of DDAA and Azone.