Abstract
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. The passive permeability coefficient for hisetal was found to be 0.93 × 10 −5 cm h −1. In comparison to the permeation across hairless mouse skin (findings of part I (Ruland et al., Int. J. Pharm., 101 (1994) 57–61) the permeability coefficient was decreased by a factor of 6. Enhancer treatment led to an increase in permeability by a factor of maximally 6 (OA). The relatively new permeation enhancers DDAA and DAIPD were found to increase the permeation of hisetal to similar extents as Azone ®. In order to show that the decreased enhancer effects were not due to the experimental design, a second set of investigations was carried out. Whereas drug and enhancer were applied simultaneously during the first set, in the second set of investigations the human skin was pretreated with neat enhancer for 3 h. The results from this second set did not differ significantly from those of the first set. Consequently, these results combined with the findings of part I (hairless mouse skin penetration) clearly demonstrated that hairless mouse skin is influenced by enhancer treatment in an exaggerated manner.
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