The development of safe and effective generic topical products is complicated by the time-consuming and costly clinical trials necessary to prove BE. The purpose of this presentation is to propose an innovative IDM method to assess BE of topically delivered drugs reaching the dermis. The method is demonstrated by applying it to the results of a 3-way dose proportionality study of iontophoretically delivered propranolol in 4 subjects. Dermis concentrations underneath the iontophoresis device were experimentally determined, and the input rates were estimated as previously described (Proceedings of " Perspectives in Percutaneous Penetration," 6th Int. Conf., 1998, Leiden, N). Input rates increased linearly with the current density, with negligible intersubject and intrasubject variability. No relationship was observed with the steady state concentrations. Input rates were used to assess BE between identical doses and discriminate among different ones. We selected, in turn, one of the experiments as the reference and the others as the test ones. The treatments were considered bioequivalent if the ratio of test/reference was in the range 0.80-1.25. The method confirmed BE 8 of 9 times and failed to detect inequivalence 3 times out of 28. These results are very encouraging given the limited number of studies, and the small difference between the doses.
ASJC Scopus subject areas
- Pharmacology (medical)