Present study is intended to formulate and evaluate the piroxicam (PXM) colon-specific enteric- coated matrix tablets using time-dependent polymers hydroxypropyl methylcellulose K4M and PH-sensitive Eudragit S100 that delays the release of drug (PXM) in the upper gastrointestinal system and also helps in the continuous release of PXM in colon area in inflammatory bowel disease (IBD). Enteric-coated tablets containing a combination of the above polymers can prevent PXM from entering the upper gastrointestinal system (i.e. stomach and small intestine).A promising system for delivering PXM to the colon was found in the in-vitro drug release studies with formulation F10. The zero-order model was best fitted for the release pattern of the above formulations. The mechanism involved in drug release was a non-fickian (super case-II) transport system. There was no interaction found in the FTIR spectral studies between the PXM and the excipients, concluding the development of HPMC K4M-Eudrgit S100 enteric-coated tablet as a viable strategy for treating inflammatory bowel disease by targeting the PXM in colon