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 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 microgram/cm2 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 microgram/cm2 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.
Hanif
R M
RM
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Qineng
P
P
Zhan
G
G
D000180:Acrylic Resins; D000818:Animals; D004337:Drug Carriers; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*
D000180:Acrylic Resins; D004337:Drug Carriers; D013729:Terpenes; C006903:carbopol 940; C063573:3,7-dimethyloctan-1-ol; D005472:Fluorouracil