Microparticles of naproxen with Eudragit RS and talc were prepared by the spherical crystallization technique, i.e. quasi-emulsion solvent diffusion method. The obtained microparticles were evaluated by micromeritic properties, yield, encapsulation efficiency, drug physical state and dissolution rate of drug. The influence of formulation factors and preparation condition (drug: polymer ratio, talc: polymer ratio, SLS concentration, stirring speed) on the properties of the microparticles were also examined. The resultant microparticles were finely spherical and uniform with high incorporation efficiency and yield. Greater encapsulation efficiency was obtained by increasing the drug: polymer ratio and talc: polymer ratio and by reducing the SLS %. The dissolution rate of naproxen from microparticles was enhanced significantly with increasing the ratio of drug: polymer and stirring rate, and sustained by increasing SLS % in crystallization medium. The results of X-ray diffraction and differential scanning calorimeter analysis indicated that naproxen was highly dispersed in microparticles, so as amorphous state. Studies carried out to characterize the micromeritic properties of formulations, such as flowability and packability showed that microparticles were suitable for further pharmaceutical manipulation (e.g. capsule filling). Hence, the spherical crystallization technique can be successfully used for obtaining spherical microparticles, generating a heterogeneous matrix system and providing sustained drug release.