Abstract: OBJECTIVE To optimize the formulation of sustained-release tablets with Polyox^® mixture as hydrogel matrix and to study its release mechanism in vitro. METHODS The formulation was optimized based on the relationship between the ratio of Polyox^® mixture and the release rate. The release mechanism was studied by comparing the release ratio with the erosion ratio in vitro. The release profiles of drugs with different solubility were analyzed. RESULTS The drug release rate in vitro was linear with the ratio of Polyox^® N60K and WSR303. Drug release profile in vitro of the optimal formulation obeyed the zero-order release model within 12 h(r=0.992 5) and almost synchronized with its erosion profile. The release profiles of drugs with different solubility were similar at 20% of drug content. CONCLUSION The matrix tablets made of Polyox^® showed excellent properties in sustained drug delivery and its drug release mechanism consisted of drug diffusion and matrix erosion.