INTRAOCULAR DRUG-DELIVERY - IN-VITRO RELEASE STUDIES OF 5-FLUOROURACIL FROM N-1-ALKOXYCARBONYL PRODRUGS IN SILICONE OIL

Various N-1-alkoxycarbonyl prodrugs of 5-fluorouracil (5-FU) ranging f rom 5 to 18 carbon units in the pro-moiety were synthesized. The compo unds were physico-chemically characterized by determining the ionizati on constant (K-a), aqueous solubility (S), octanol/water partition coe fficient (P), and the degradation rate in aqueous solution at differen t pH values. The in vitro degradation rate of the prodrugs in calf ser um, human plasma, and rabbit vitreous humor was also investigated. Dru g delivery systems were prepared by dissolving or dispersing 5-FU prod rugs in silicone oil 1000 (SO-1000). The release of 5-FU seemed to fol low the square root of time kinetics until more than 60% of the drug h ad been released. The release rate of 5-FU was found to-decrease with increased lipophilicity of the prodrug.