Targeted drug delivery into the colon is highly desirable for local treatment of a variety of bowel diseases such as ulcerative colitis, Crohn’s disease, amebiosis, colonic cancer, local treatment of colonic pathologies, and systemic delivery of protein and peptide drugs. The colon specific drug delivery system (CDDS) should be capable of protecting the drug en route to the colon ie drug release and absorption should not occur in the stomach as well as the small intestine, and neither the bioactive agent should be degraded in either of the dissolution sites but only released and absorbed once the system reaches the colon. The present investigation is aimed to formulate the Eight formulations of Esemoprazole were developed by direct compression technique enteric coated by cellulose acetate pthalate. The F6 formulation was found to be best of all the trials showing that the drug release matches with the brand product. The best formulation F6 can successfully be employed as a controlled release of drug delivery system. The tablets can control the fluctuations in the plasma drug concentration, increase the gastric residence time and eventually improve the bioavailability of the drug.