Production of drug nanoparticles is an effective strategy to enhance solubility and oral absorption of water-insoluble drugs. The handling of drug nanoparticles has been an important issue in drug formulation because nanoparticles easily aggregate each other and redispersion of these particles is very difficult. In the present study, we developed a unique two-solution mixing type spray nozzle that can prepare drug nanoparticles in microparticles in one step without any common solvent and surfactant, and then, the prepared formulation were evaluated. Ethylcellulose (EC) and mannitol (MAN) were used as a model polymer of water-insoluble compound and a water-soluble carrier, respectively. We characterized the EC/MAN microparticles produced by the novel spray nozzle when customizing the nozzle parts to mix EC and MAN solution. Relatively smaller EC nanoparticles (<110 nm) in MAN microparticles (approximately 3 µm) were obtained by changing the customizable parts in the nozzle. In addition, the core of EC nanoparticles (<50 nm) was also observed by atomic force microscopy. We also found that the mixing time in the nozzle parts affected the size and the standard deviation of EC nanoparticles. These results suggest that the size of EC nanoparticles in MAN microparticles is controllable by using this unique nozzle. After all, we could prepare MAN microparticles containing EC nanoparticles in one step by using the novel nozzle. The drug/MAN microparticles formulation produced by the nozzle may be useful for the handling of drug nanoparticles.