PENETRATION ENHANCING EFFECT OF TETRAHYDROGERANIOL ON THE PERCUTANEOUS-ABSORPTION OF 5-FLUOROURACIL FROM GELS IN EXCISED RAT SKIN

Poly(acrylic acid) gels containing 5-fluorouracil (5-FU) and tetrahydr ogeraniol (THG) were prepared and the effects of THG on 5-FU permeatio n across the excised rat skin were studied by in vitro methods. Experi ments on in vitro permeation of 5-FU across the skin with vertical dif fusion cells showed that addition of THG to the gels markedly enhanced the 5-FU permeability. Increasing the THG concentration in the gels t o 8% proportionally increased the permeability of 5-FU. More than 12 h was required to reach a steady-state level of 5-FU after administrati on 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 mu g/cm(2) per h, an d the enhancement ratio of 31.22+/-1.18 when the THG concentration was 8%. Synergistic effects of propylene glycol (PG) with THG were also i nvestigated and a maximum flux of 256.81+/-9.15 mu g/cm(2) per h, was obtained when the PG concentration was 5% and THG was 8%. The correspo nding enhancement ratio was 31.71+/-1.13. These results suggest not on ly 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 practi cally unabsorbable drugs. (C) 1998 Elsevier Science BN.