Effect of enhancers and retarders on percutaneous absorption of flurbiprofen from hydrogels.
The effect of enhancers/retarders on the transdermal absorption of flurbiprofen from cellulose hydrogels was studied in vitro. The release rate of flurbiprofen and the viscosity of hydrogel matrices were also examined. The flux of flurbiprofen from cellulose hydrogels approximated that from aqueous buffers, whereas the skin reservoir of flurbiprofen was lower with hydrogels. Incorporation of the cosolvents, propylene glycol (PG) and ethanol, did not significantly increase skin absorption of flurbiprofen. Ethanol even reduced the skin reservoir of the drug. Oleic acid, an unsaturated fatty acid, produced the largest skin reservoir of the drug when incorporated into the hydrogels. D-Limonene, a cyclic monoterpene, showed the greatest ability to enhance the flux of flurbiprofen. However, phospholipids as retarders markedly reduced the skin absorption of flurbiprofen. The mechanisms by which enhancers/retarders govern flurbiprofen permeation were elucidated by in vitro permeation studies using various skin types (enhancers/retarders-pretreated skin, stratum corneum (SC)-stripped skin, and delipidized skin) and histological examination. The results suggest different mechanisms and skin structural modifications caused by different enhancers/retarders.
Fang
Jia-You
JY
Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan. fajy@mail.cgu.edu.tw
Hwang
Tsong-Long
TL
Leu
Yann-Lii
YL
D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020100:Hydrogels / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology
D020100:Hydrogels; D005480:Flurbiprofen