Penetration enhancing effect of tetrahydrogeraniol on the percutaneous absorption of 5-fluorouracil from gels in excised rat skin

Abstract

Poly(acrylic acid) gels containing 5-fluorouracil (5-FU) and tetrahydrogeraniol (THG) were prepared and the effects of THG on 5-FU permeation across the excised rat skin were studied by in vitro methods. Experiments on in vitro permeation of 5-FU across the skin with vertical diffusion cells showed that addition of THG to the gels markedly enhanced the 5-FU permeability. Increasing the THG concentration in the gels to 8% proportionally increased the permeability of 5-FU. More than 12 h was required to reach a steady-state level of 5-FU after administration of 5-FU–THG gel topically. The permeability parameters such as flux, permeability coefficient and enhancement ratio were determined. The results indicated a maximum flux of 252.91±9.61 μg/cm 2 per h, and the enhancement ratio of 31.22±1.18 when the THG concentration was 8%. Synergistic effects of propylene glycol (PG) with THG were also investigated and a maximum flux of 256.81±9.15 μg/cm 2 per h, was obtained when the PG concentration was 5% and THG was 8%. The corresponding enhancement ratio was 31.71±1.13. These results suggest not only that THG would be very useful for increasing the skin permeability of 5-FU, but also that THG being a natural product might be useful for developing transdermal therapeutic systems for the delivery of practically unabsorbable drugs.