STATISTICAL OPTIMIZATION FOR DEVELOPMENT OF COLON TARGETED pH DEPENDANT METRONIDAZOLE GRANULES USING FULL FACTORIAL DESIGN

The objective of this study was to evaluate and optimize Eudragit concentration and coating level on metronidazole release from granules for colon delivery using 3² full factorial design. Independent variables selected were Eudragit conc. (10, 15 and 20%) and coating level (10, 15 and 20%), the evaluated responses were percent drug release at 5 h, 24 h and time to release 50% of the drug. The dissolution was carried out at different pH media of 1.2, 7.4 and 6.8. The dissolution data revealed that polymer conc. and coating level were having significant role in achieving optimum formulation. Using surface response, contour plot and statistical equations, the optimum formulation consisting of 15% of polymer conc. and 20% coating level was predicted. Experimental data showed that the granular formulations releases no drug at pH 1.2 (simulating stomach) and only 12.85 ± 1.63% at pH 6.8 (simulating small intestine) and controlled at pH 7.4. The result of this study showed that the factorial design is a suitable tool for optimization of coating for colon delivery. The optimized formulation produced dissolution profiles that were close to predicted values.