Formulation factors for preparing ocular biodegradable delivery system of 5-fluorouracil microparticles

Microparticles containing 5-fluorouracil (5-FU) were prepared using poly(DL -lactide-co-glycolide) with an oil-in-oil emulsion/solvent extraction techn ique. Particle characteristics including size distribution, 5-FU loading ef ficiencies, in vitro release and degradation were investigated. The dispers ed phase was composed of PLG dissolved in dichloromethane, and the continuo us phase was paraffin oil containing lecithin. 5-FU was successfully entrap ped in the microparticles with trapping efficiencies up to 76%, loading lev el 10% w/v, and particle size 3 mum. Release profiles of 5-FU loaded microp articles were determined to follow a first-order-time relationship. An opti mized preparation of 5-FU microparticles was achieved and was capable of co ntrolling the release of 5-FU over 21 days with an in vitro delivery rate o f 0.4 mug 5-FU/mg particles/day in the study. Preliminary animal studies in dicated that the 5-FU loaded microparticles as an ocular delivery system sh owed no ocular toxicity and no significant inflammatory response in rabbits for 2 months. The 5-FU loaded microparticles approach, with PLG, might be a potential for the application of long-term delivery of hydrophilic drugs in the eye.