The aim of the study was to develop and evaluate enteric‐coated matrix tablet of Aceclofenac for colonic delivery by exploiting prolonged release characteristics of HPMC K4M with pH dependent solubility property of a Eudragit S100. Extended release matrix tablet were prepared by direct compression of hydrophilic polymer HPMC and other ingredients. The pH dependent release was achieved by coating matrix tablet with Eudragit S100, soluble at pH 7. All the formulations of 32 factorial design (A1- A9) were evaluated for the physicochemical parameters and subjected to in vitro drug release in 0.1 N HCl for two hour, three hour in pH 5.2 Phosphate buffer then in pH 7.4 phosphate buffer up to 17 hrs. Multiple regression analysis, two way ANOVA followed by Tukey test were performed. Polynomial equations and response surface plots were generated for all dependent variables. It was observed that both the factors had significant effect on dependable variables (Q6, Q12, Q17 and n, k). The formulation A5 was most likely to provide targeting of aceclofenac in the colon owing to its minimal release of the drug in the first 5 hr and give release up to 17hr with 62.21 similarity factor.