For many water insoluble acidic or alkaline drugs, amorphization and nanonization represent an effective bioavailability enhancement strategy. Cefixime (CFX) was chosen as a model drug, and amorphous nanoparticles were prepared via a typical process intensification technology: high-gravity reactive precipitation (HGRP). The effects of temperature, rotating speed, overall flow rate, and drug concentration on the particle size and size distribution were investigated. Under the optimum conditions, spherical nanoparticles with a mean size of 45 nm could be precipitated. After filtration, redispersion and spray-drying processes, the obtained CFX nano-powder showed a good stability and exhibited a tremendously enhanced saturation solubility, reaching similar to 11 times higher than that of raw CFX. Furthermore, CFX nano-powder achieved 100% drug dissolution within 2 min while raw CFX did not dissolve completely after 45 min. Since the production capacity of lab-scale RPB reached 2.3 kg/h, HGRP method might offer a general platform for mass production of drug nanoparticles without the use of organic solvents and pharmaceutical additives. (c) 2016 Elsevier B.V. All rights reserved.