Controlled release tablets having near zero-order release of diltiazem HCl a water ?soluble drug were prepared using guar gum (GG) in matrix core and Sodium carboxy methylcellulose (SCMC) as barrier layers. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. It indicated the nature of drug release from the matrix tablets and layered matrix tablets followed non-Fickian diffusion and super case II mechanism respectively. Mean dissolution time (MDT) for the formulations D3 and D3L3 were found to be 4.17h and 16.45h, while Dissolution Efficiency (DE8%) decreases, indicating that the release of drug is slower from layered matrix tablets. On the basis of in vitro release data, D3L3 was subjected to bioavailability studies in human healthy volunteers. Cmax and tmax following oral ingestion of D3L3 and Dilzem SR were found to be 172.41ng/ml (±5.11), 6.00hrs (±0.01) and 360.82ng/ml (±5.65), 3.12hrs (±0.12) respectively. AUC0-∞ for D3L3 and Dilzem SR were found to be 3414.19ng/ml/h (±179.49) and 2623.28ng/ml/h (±48.45) respectively. The in vivo characterization of diltiazem HCl in human volunteers from formulation D3L3 showed delayed Tmax unaltered bioavailability indicating a slow and controlled release of the drug from layered matrix tablets.