To enhance the solubility and dissolution rate, and thus potentially improve the oral bioavailability of cefixime (CFX), amorphous CFX nanoparticles were prepared via high-gravity antisolvent precipitation (HGAP) without the aid of any pharmaceutical additives in a rotating packed bed (RPB). The effects of operating variables on particle size and distribution were investigated. Compared to raw CFX, the mean size of prepared nanoparticles decreased greatly from about 2.1 mu m to 57 rim, and the saturation solubility increased tremendously from 0.289 to 0.951 mg/mL. CFX nanoparticles showed good stability and were capable of generating a maximum supersaturation level, reaching up to similar to 22.8 times of raw CFX's saturation solubility. Further, CFX nanoparticles achieved 100% drug dissolution within 2 min, while the raw drug did not dissolve completely after 45 min, suggesting that the solubility and dissolution properties of CFX nanoparticles were significantly improved. Since the drug recovery ratio achieved 99.9%, and the production capacity of lab-scale RPB with a continuous operation reached 1.8 kg/h, the HGAP method might offer a general and facile platform for mass production of CFX nanoparticles.