Volumes Archive
Vol. 45, Number 3, 2003
Evaluation of Hydroxyethyldiclofenac as Possible Prodrug for Topical Application
Jamal Jilani, Aymen Shatnawi and Naser Idkaidek
Department of Medicinal Chemistry and Pharmacognosy.Department of Pharmaceutical Technology. Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid, Jordan
Abstract
In vitro permeability of 2-hydroxyethyldiclofenac (a possible diclofenac prodrug), diclofenac sodium and diclofenac diethylamine through rat skin were studied using Franz diffusion cells. The partition coefficients of 2-hydroxyethyldiclofenac and diclofenac diethylamine between 1-octanol and acetate buffer at pH 7.4 were 100.6 and 30.97, respectively while the solubilites of2-hydroxyethyldiclofenac, dic10fenac sodium and diclofenac diethylamine were 0.08,21.97, and 17.73 mg/ml respectively. The prodrug was chemically stable in the donor solution (5% propylene glycol and methanol) and in the receptor solution (20% propylene glycol and acetate buffer pH 7.4) throughout the time of the experiment On the other hand, it hydrolyzed totally in the skin and only the parent drug was detected in the receptor solution. Diffusion experiments through rat skin showed a greater steady slate flux for 2-hydroxyethyldiclofenac by 30% and !2% higher than diclofenac sodium and diclofenac diethylamine respectively, Addition of the penetration enhancers, dimethylsulfoxide and dimethylformamide, increased the steady state flux of 2-hydroxyethyldiclofenac about by 4 fold, while the addition of polysorbate 60 had no effect on the penetration of the prodrug.
Key words: Diclofenac; prodrug; NSAID; topical application; penetration enhancer.
