In this study, ondansetron was encapsulated using hydroxypropyl methyl cellulose (HPMC) mixed with a water-insoluble polymeric barrier using EuRS RS 100 (EuRS), which was expected to be effective in preventing premature drug release. This microcapsule containing ondansetron was prepared using oil-in-water (O/W) solvent evaporation method and confirmed by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The morphology and particle size of the microcapsules were observed by scanning electron microscopy (SEM). In addition, the drug release behavior of the microcapsules with different EuRS contents were determined by UV/Vis spectroscopy. From the results, the microcapsules were successfully fabricated in all cases, $28-49{mu}m$ in size. The drug release rate was decreased with increasing EuRS ratio, which was likely due to the increasing content of quaternary ammonium groups on EuRS.