Abstract: OBJECTIVE To prepare brucine push-pull osmotic pump controlled release tablets, obtain optimal formulation by orthogonal design, and to investigate the release mechanism. METHODS The percent of cumulative release and whether the drug release curve was linear were used as the evaluation standard for the drug release profile in vitro. The effects of amounts of PEO N750, PEO Coagulant, PEG 4000 and coating weight were studied through single-factor method. Based on the single-factor study, the optimal formulation of brucine push-pull osmotic pump controlled release tablet was selected via orthogonal design. The release in vitro of the optimized formulation was also fitted to different models. RESULTS The results of orthogonal design showed that amounts of PEO Coagulant had significant effects on the drug release in vitro (P<0.05). The optimal prescription:PEO N750 was 175 mg, PEO Coagulant was 65 mg, PEG 4000 was 11%, weight gain of coating was 7%. The release rate of brucine push-pull osmotic pump controlled release tablets with optimized formulation was constant, and the cumulative release could reach 93.14%. CONCLUSION The prepared of brucine push-pull osmotic pump controlled release tablets show excellent zero-release profile in 12 h, which could control the release of brucine from push-pull osmotic pump tablets.