Most of the highly active drugs on the market are water-insoluble, which indicate low biological utilization and side effect due to their low solubilities among other characteristics.Ibuprofen is a non-steroidal anti-inflammatory drug relatively insoluble in water used to treat rheumatoid arthritis, osteoarthritis, and the relief of moderate pain.Ibuprofen has poor solubility in water, which leads to the requirement for the solubility improvement of the drug by reducing particle size or developing formulations for its bioavailability [1].In the past two decades, vast supercritical fluids (SCF)-assisted particle formation technologies have been applied instead of conventional approaches, e.g., rapid expansion of supercritical solutions has been reported to be used to produce ibuprofen particles in micro-size [2, 3] but with obvious dissolution rate increase;some studies used supercritical impregnation to produce methyl-β-cyclodextrin/ibuprofen composite particles to enhance the dissolution rate of ibuprofen [4].Previously, we reported a supercritical fluid-based approach [5] for preparing nanoparticles of Coenzyme Q10.The process consists of two steps: PEG6000 / ibuprofen composite particles were prepared by a modified PGSS (particles from gas-saturated solutions) process;the PEG6000 was washed away from the composite to obtain Coenzyme Q10 nanoparticles.In this work, the same method is applied to ibuprofen by virtue of PEG6000/ibuprofen system is miscible before the PGSS process.The effects of pressure, temperature, mass-fraction of ibuprofen on the ibuprofen particle size and particle morphology were investigated.Results show that ibuprofen particles with sizes of 20-500nm are produced at different conditions.Finally, the dissolution of different ibuprofen particles were studied and compared, indicating the dissolution of ibuprofen nanoparticles is obviously enhanced.