Abstract: OBJECTIVE To optimize the formulation of propranolol hydrochloride microcapsules. METHODS Propranolol hydrochloride microcapsules were prepared by fluidized bed. The effects of influence factors such as the flow rate of capsule material solution and spray pressure, on mean diameter, entrapment efficiency, drug loading and overall desirability were investigated by using central composite design and response surface method. The data were imitated using multi-linear equation and second-order polynomial equation. RESULTS The latter was prior to the former considering from multiple correlation coefficients. The best process conditions were as follows: the flow rate of capsule material solution of 1.00 mL·min^-1 and spray pressure of 0.65 bar. Under the optimal conditions, the mean diameter, entrapment efficiency, drug loading of the propranolol hydrochloride microcapsules were 300 μm, 20.54% and 89.63%. CONCLUSION The optimized preparation technique for the propranolol hydrochloride microcapsules with fluidized bed is stable, feasible, with high entrapment efficiency. It can be used for the industrial manufacture.