Optimization of a Novel Oral Colon Delivery System of Indomethacin Using Full Factorial Design

Purpose: To develop and optimize indomethacin (IDM) matrix tablets for specific colon drug delivery. Methods: Indomethacin matrix tablets containing hydrogenated castor oil (HCO), and pectin (PEC) were prepared by hot fusion method. A 32 full factorial design was used to investigate the combined effect of two independent formulation variables, X1 and X2, namely, the amount of HCO and PEC, respectively. Their effect on IDM release from the matrix tablets in acidic medium (0.1 N HCl) and phosphate buffer (pH 6.8), were analyzed and optimized. A contour plot was also applied to graphically represent the effect of the independent variables on drug release in pH 6.8 medium at 2 h (Y1) and 24 h (Y2), and the time required for 25 % drug release (Y3) as dependent variables. Results: The optimized IDM matrix tablets showed almost total retardation of drug release in acidic medium and prolonged sustained release in pH 6.8 medium over 24 h. The correlation coefficient (R2) value for Y1, Y2 and Y3 were 0.99850, 0.9980 and 0.9970, respectively, indicating good correlation between dependent and independent variables. Differences between the coefficients for Y1, Y2 and Y3 were significant (p < 0.05), and hence contributed significantly to the prediction of the independent variables. Conclusion: The findings indicate that successful design, development, and optimization of IDM matrix tablets for colon delivery has been achieved.