The aim of the present study is to develop colon-targeted drug delivery systems for diclofenac sodium which release the drug specifically and instantly at target site using amylose as a carrier. Coating formulations were designed based on the full factorial design. The evaluated responses were lag time prior to drug release and T90. Compression-coated tablets of diclofenac sodium containing various proportions of amylose and HPMC were prepared. In vitro drug release studies were done by changing pH method with enzyme. In vivo studies were done to confirm the potential of formulation to release the drug at target site. The dissolution data revealed that the ratio of polymers is very important to achieve optimum formulation. Results showed that the tablet prepared according to the above formulation released drug instantly at pH 6.8 (simulating colonic pH). An in vivo study shows that optimized formulation disintegrated in the target region. The results of this study revealed that factorial design is a suitable tool for optimization of coating formulations to achieve colon delivery. It was shown that coating formulation consisting of amylose 285 mg and HPMC 150 mg coating has the potential for colonic delivery of diclofenac sodium irrespective of change in pH in a patient with IBD.