TRANSDERMAL DELIVERY OF THE TETRAPEPTIDE HISETAL (MELANOTROPIN (6-9)).2. EFFECT OF VARIOUS PENETRATION ENHANCERS - IN-VITRO STUDY ACROSS HUMAN SKIN

The percutaneous absorption of the tetrapeptide hisetal as well as the effect of various penetration enhancers on the permeation of hisetal across human skin was evaluated by in vitro methods in Franz cells. Th e passive permeability coefficient for hisetal was found to be 0.93 x 10(-5) cm h(-1). In comparison td the permeation across hairless mouse skin (findings of part I (Ruland et al., Int. J. Pharm., 101 (1994) 5 7-61) the permeability coefficient was decreased by a factor of 6. Enh ancer treatment led to an increase in permeability by a factor of maxi mally 6 (OA). The relatively new permeation enhancers DDAA and DAIPD w ere found to increase the permeation of hisetal to similar extents as Azone(R). In order to show that the decreased enhancer effects were no t due to the experimental design, a second set of investigations was c arried out. Whereas drug and enhancer were applied simultaneously duri ng the first set, in the second set of investigations the human skin w as pretreated with neat enhancer for 3 h. The results from this second set did not differ significantly from those of the first set. Consequ ently, these results combined with the findings of part I (hairless mo use skin penetration) clearly demonstrated that hairless mouse skin is influenced by enhancer treatment in an exaggerated manner.