ENHANCEMENT OF TRANSDERMAL PENETRATION OF DAPIPRAZOLE THROUGH HAIRLESS MOUSE SKIN

The in vitro permeation rate of dapiprazole base (DAP-B) through hairl ess mouse skin was investigated, as a preliminary step towards the dev elopment of a transdermal therapeutic system. The study involved the e valuation of the permeability coefficient of the drug applied to the s kin in a series of liquid and semisolid vehicles, both in the absence and in the presence of different penetration enhancers. In liquid vehi cles the permeability coefficient of DAP-B was significantly promoted (up to 73 times) by some terpenes (l-limonene, alpha-bisabolol, terpin olene) and by a mixture of unsaturated fatty acids. Similar effects we re noted in semisolid vehicles, although the permeability coefficients were lower. Iontophoretic experiments on DAP-B in physiological salin e solution, at constant current densities in the range of 0.05 - 0.5 m A/cm(2), produced up to 115-fold permeability increases relative to pa ssive diffusion. The present results, even if needing further corrobor ation by tests on human skin, evidenced the activity of some molecules as skin permeation enhancers for DAP-B, and confirmed the synergy bet ween propylene glycol and the enhancers, already reported in the liter ature. The possibility of promoting DAP-B transport through the skin b y iontophoresis was also established.