Abstract： Objective To optimize the preparation of aripiprazole(APZ)long-acting injectable suspension(LAIs).Methods APZ LAIs were prepared by high-shear rotor-stator wet milling.Effect of types of the rotor-stator,rotation tip speed,gaps of the rotor-stator,concentrations of suspension agent,drug concentrations and material temperature on the particle size were determined.APZ LAIs were characterized by surface morphology,in vitro release and the sustained release effect in vivo,and compared with samples prepared by wet media milling.Results The optimal conditions for the preparation of APZ LAIs included module colloid mill as a shear tool,the drug concentration at 13％,the carboxymethylcellulose sodium concentration at 0.52％,the pH of excipients solution at 5.0～6.0,the rotation tip speed at 35 m·s-1,the gap of the rotor-stator at 100 μm,and the material temperature at 48～65 ℃.The obtained average particle size of APZ LAIs was(3.83±0.05)μm.Compared with the samples prepared by wet media milling,APZ LAIs had better dispersion without aggregation,with smoother surface and shape,and more excellent sustained release effect in vitro and vivo.Conclusion The preparation of APZ LAIs is simple and convenient,feasible for mass production.This study provides a reference for the development of other drugs.