Preparation and in vitro release behaviour of 5-fluorouracil-loaded microspheres based on poly (L-lactide) and its carbonate copolymers

Abstract

A modified oil-in-oil (o/o) emulsion solvent evaporation technique was adopted to prepare 5-fluorouracil (5-Fu)-loaded poly (L-lactide) (PLLA) or its carbonate copolymer microspheres. The disperse phase was a drug:polymer solution using a solvent mixture of N, N-dimethylformamide (DMF) and acetonitrile and the continuous phase was liquid paraffin containing 1–10% (w/v) Span 80®. The effects of preparative parameters, such as the composition of the inner oil phase, drug:polymer ratio, polymer concentration and agitation rate, on 5-Fu entrapment efficiency and microsphere characteristics were investigated. By introducing 25% (v/v) DMF into the inner oil phase, microspheres with high drug entrapment efficiency and an ameliorated burst effect were achieved. Using this modified method, microspheres with various particle sizes could be produced with a high 5-Fu entrapment efficiency (about 80%). In vitro drug release tests showed a burst release of 5-Fu from PLLA microspheres, followed by a sustained release over 50 days. In the case of poly (L-lactide-co-1,3-trimethylene carbonate) (PLTMC) and poly (L-lactide-co-2,2-dimethyl-1,3-trimethylene carbonate) (PLDTMC), the drug release could be continued for over 60 days.

Key Words:

• 5-Fluorouracil
• poly (L-lactide) and copolymers
• microspheres
• controlled drug release