OPTIMIZATION OF IN-VITRO NIFEDIPINE PENETRATION ENHANCEMENT THROUGH HAIRLESS MOUSE SKIN

The ability of penetration enhancer/solvent combinations of homologous members of alcohols and alkanoic acids in combination with Atone and isopropyl myristate to accelerate delivery rates of nifedipine was eva luated. Several alkanols and alkanoic acids were found to enhance the in vitro permeation of nifedipine (N) through excised hairless mouse s kin. A McLean Anderson experimental design permitted the results of th e permeation studies to be interpreted in a stoichiometric fashion. Th e permeation process was modeled so that simultaneous predictions of t he flux or lag time could be made. Regression analysis identified posi tive synergistic interactions among the formulation components propyle ne glycol (PG), cis-oleic acid (OA), and dimethyl isosorbide (DI)-whic h strongly affected nifedipine (N) permeation. Of the mixtures tested, a mixture of PG, OA, and DI yielded optimal flux and lag time. Flux v alues fourfold higher than that required to deliver an equivalent oral daily dose in man were observed with hairless mouse skin. These resul ts suggest that it may be feasible to percutaneously deliver clinicall y useful amounts of N by the judicious choice of Vehicle composition. (C) 1998 Elsevier Science B.V. All rights reserved.