Formulation and Optimization of Controlled Release 5-Fluorouracil Tablets for Colonic Delivery

Abstract

: Objective: Formulations were developed for targeted controlled delivery of 5-fluorouracil at the colonic site. Methods: Probable dose for drug loading in the tablets and duration of drug release at the colon was determined. Core tablets were formulated with an aim to deliver the drug at a constant rate following zero order kinetics throughout the duration of release. Hydroxypropyl methylcellulose E15 and potassium chloride were incorporated as hydrophilic agents in the core matrix for drug release at the desired level and the formulation with the best release profile was chosen for coating with a coating solution containing Eudragit S100, polyethylene glycol 400 and talc. The amounts of Eudragit S100 and weight gain of the tablet were optimized using sequential simplex optimization method. Results: The optimized coated formulation (0.6875 g of Eudragit S100; 7.5% weight gain) was able to provide minimum drug release in the 5 hr lag time (5.9% of cumulative release) and an average release rate of 19.8% per hr thereafter. Conclusion: The optimized formulation for 5-Fluorouracil delivery at the colonic site was able to achieve a sufficient lag time and controlled drug release and can be highly beneficial for optimum therapeutic activity and negligible side effects when administered orally.Key words: Colonic delivery, Eudragit S100, Hydroxypropyl methylcellulose E15, Potassium chloride, Sequential optimization, Zero order release.