Factorial design approach to evaluate interactions between electrically assisted enhancement and skin stripping for delivery of tacrine

The objective of this work was to study the mechanisms of action of iontophoresis and electroporation and their interaction effects on delivery of tacrine hydrochloride in vitro across intact and stripped rat skin. Experiments were done according to a full factorial design, to quantify the effects of iontophoresis (X-1), electroporation (X-2) and stripped skin (X-3) alone and in combination on cumulative drug delivery at 6 h. Mathematical model eliciting the main effects of the factors and their interaction on cumulative tacrine delivery in 6 h shows that all three techniques examined alone have a positive impact on the permeation of tacrine, the greatest enhancement in delivery achieved by iontophoresis. However, iontophoresis in combination with electroporation or skin stripping yielded no improvement in delivery compared to iontophoresis alone. The most significant enhancement is seen when all three methods of assisted delivery are done in combination. Iontophoresis appears to control drug delivery to the exclusion of other enhancement methods. Electroporation appears to cause formation of a large depot of tacrine in the skin. (c) 2004 Elsevier B.V. All rights reserved.