OBJECTIVE: To optimize the formulation of metoprolol tartrate sustained-release tablets in compound hydrochlorothiazide double layer tablet.METHODS: The formulation of metoprolol tartrate sustained-release tablets was optimized using orthogonal experiment with release rate in vitro as index,total amount of HPMC and carbomer (A) and its ratio (B),amount of MCC (C) and the concentration of PVP ethanol solution (D) as factors.RESULTS: The optimal formulation was as follows: A=30%,B=1 ∶ 2,C=20% and D=5%.Accumulative release rate of 3 batches of metoprolol tartrate sustained-release tablet prepared by optimized formulation were 25%～45% within 1 h,40%～75% within 4 h,more than 75% within 8 h and more than 90% within 24 h.CONCLUSION: Optimized formulation of metoprolol tartrate sustained-release tablets is reasonable and simple.