Colon-targeted drug delivery is highly desirable to prevent stomach degradation and to provide local treatment in a variety of bowel diseases. The objective of this study was to develop controlled release microbead formulation of prednisolone using pH sensitive polymer Eudragit RS100 for targeted drug delivery to colon for the treatment of inflammatory bowel disease. In the present study, prednisolone (P) loaded sodium alginate (SA) microbeads (MB) were prepared by ionotropic-gelation technique using three different polymers HPMC, chitosan, and pectin. The beads were coated with Eudragit RS100 to protect them from gastric fluid and specific release in the colonic area. All the formulations were evaluated for encapsulation efficiency, flowability, compressibility and in vitro drug release. The batch F6 was found to have minimum drug release (6%) in simulated gastric fluid pH 1.2 and maximum (91.24%) in phosphate buffer saline pH 7.4 which indicates its colon specific drug release. The final formulation was selected based on the high encapsulation efficiency, and maximum drug release and good flow properties. The optimized batch (F6) was further investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction analysis (XRD) and found to be amorphous in nature. The morphology of the optimized formulation was characterized using Scanning Electron Microscopy (SEM) and was found porous structure of the microbeads which causes rapid drug release. From the results, it can be concluded that this pH variable formulation is able to achieve site-specific, sustained release drug delivery to the colon following oral administration and could providing a promising strategy to eliminate the adverse effects on non-targeted organs.