In the present study, an effort was made to develop the pulsatile drug delivery of Tramadol hydrochloride to the colon. A time delayed capsule was prepared by sealing the microspheres inside the insoluble hard gelatin capsule body with erodible hydrogel plug. The microspheres were prepared by emulsion solvent evaporation technique... Optimized microsphere formulations were selected based on dissolution studies. The entire device was enteric coated, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. Hydrogel plug (HPMCK100 and lactose in 1:1 ratio) having 4.5kg/cm2 hardness and 100 mg weight was placed in the capsule opening and found that it was satisfactory to retard the drug release in small intestinal fluid and to eject out the plug in colonic fluid and releasing the microspheres into colonic fluid after a lag time criterion of 5 hours. In order to simulate the pH changes along the GI tract, three dissolution media with pH 1.2, 7.4 and 6.8 were sequentially used. FTIR study confirmed that there was no interaction between drug and polymer. Among all the formulations Tramadol hydrochloride microspheres prepared with Eudragit RL 100 in 1:2 ratio shown prolonged release for a period of 12 hours. The obtained results revealed the capability of the system in delaying drug release for a programmable period of time and can prevent a sharp increase in the blood pressure during the early morning hours , a time when the risk of hypertension is the greatest. Keywords: Metaprolol succinate; Hypertension; Pulsatile;Microspheres; Hydrogel Plug; Solvent evaporation