The purpose of this study is to investigate the effect of ultrasound sonication time to the mean particle size, crystallite dimensions and specific surface area of naproxen sodium (NNa) active ingredient. The sonication time effect of ultrasound on the surface morphology, crystallinity, molecular structures and saturation solubility of NNa active ingredient have been examined using UV-vis spectroscopy, zeta potential, Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FE-SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) measurements. It has been determined that different ultrasound sonication time duration has changed the surface morphology and crystal structure of the drug active substances. It has been observed that ultrasonic sonication time doesn't have a linear correlation with the increase on the surface area and decrease on the particle size. On the contrary, it has been detected that optimum sonication time has a great effect on decreasing the particle size of drug active substances and increasing the surface area, therefore increasing the saturation solubility.