Vitexin is a flavonoid drug with poor water solubility commonly used to prevent heart diseases. The poor water solubility of vitexin limits its dissolution, which strongly impairs drug bioavailability. The aim of this work was to improve its bioavailability by reducing particle size in a supercritical antisolvent process (SAS) using supercritical carbon dioxide as an antisolvent agent and dimethyl sulfoxide (DMSO) as a solvent. In order to optimize the parameters of SAS process, the whole experiment was designed and conducted in an orthogonal array design (OAD), OA (16)(4(5)). The obtained optimum micronization conditions were as follows: precipitation pressure 25 MPa, precipitation temperature 50 degrees C, concentration of vitexin solution 2 mg/mL and vitexin solution flow rate at 6.7 mL/min. Under this condition, the mean particle size (MPS) of vitexin was reduced to 126 +/- 18.5 nm. In addition, both the processed vitexin particles and the unprocessed one were characterized by Scanning Electron Microscopy (SEM), Dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR). Liquid chromatography tandem mass spectrometry (LC-MS/MS), X-ray diffraction (XRD) and Differential scanning calorimeters (DSC). The results showed that SAS micronization process did not induce degradation of vitexin and the processed vitexin particles had lower crystallinity. Finally, the dissolution rates of the processed and unprocessed vitexin were evaluated, the results showed that there was a significant increase of the dissolution rate of the processed vitexin comparing with the unprocessed vitexin. Moreover, vitexin nanosuspension of high concentration can be prepared by dissolving processed vitexin in physiological saline. These results suggest that micronized vitexin may have a great potential in cardiovascular and cerebrovascular diseases therapy. (C) 2012 Elsevier B.V. All rights reserved.