Colon delivery of 5 – Fluoro uracil using cross-linked chitosan microspheres coated with eudragit S 100

Abstract

5-Fluorouracil though recommended as a chemotherapeutic agent for colorectal cancer, suffers from severe systemic toxicity and so needs site-specific delivery. Objective of present investigation is to design slow release enteric coated solid formulations to avoid drug release in stomach and upper small intestine but slowly to build up required drug concentration in the colon. Chitosan microspheres were prepared by emulsification method using gluteraldehyde as cross linking agent. The microspheres were then coated with Eudragit S – 100 by emulsion solvent evaporation method. The coated microspheres were characterized for particle size, entrapment efficiency and surface characteristics. In-vitro drug release profile was studied by changing pH media as per USP protocol and the data was subjected to kinetic interpretations. The optimized microspheres showed particle size in the range of 62 to 65 μm with 65 ± 2% drug entrapment. Eudragit coated chitosan microspheres showed particle size increase upto 390 ± 2 μm with nearly spherical shape and smooth surface. In vitro drug release profile of uncoated microspheres was typical like conventional dosage forms with 38 %, 62 % and 88 % drug release at the end of 2 hrs, 6 hrs and 10 hrs respectively. Coated microspheres showed no drug release in SGF (2hrs), negligible release (8 %) in 6hrs but substantial release of 95% in 24 hours in simulated colon media. Drug distribution in GI following oral administration of coated microspheres in wistar rats showed 84% of the drug accumulation in colon.