Extrusion-Spheronization Processing (ESP) was applied to preparate sustained release spherical particles as a form of matrix spherical particle (MSP). dl-methylephedrine HCI (ME) was the drug chosen and several dissolution retardants and binders were selected to estimate a relatively good formulation on this purpose. The effect of physicochemical nature, concentration, and solvents of these dissolution retardants and binders on regularity in shape of MSP and in vitro release rate was investigated. The effect of Particle size of matrix particles was also evaluated. It is, therefore, concluded that this ESP would be a relatively good preparation method of sustained release MSP of ME which has the sustained action of about 5 and 8 hours by formulating of ethylcellulose and ethylcellulose-paraffin as a dissolution retardant, respectively, and then ethylcellulose solution of 80% EtOH is recommended as a binder.