It is reported that nano-sizing is one of the promising methods for improving the dissolution rate and oral bioavailability of poorly water-soluble drugs. In this study, bifendate (DDB) suspensions have been successfully produced by employing two different techniques, the precipitation-ultrasonication method and the precipitation-combined microfluidization method. According to the preliminary test, in the precipitation-ultrasonication process, the concentrations of polyvinylpyrrolidone K30 (PVPK30) and lecithin in the anti-solvent, the concentration of DDB in the organic phase and the precipitation temperature were optimized at 0.05%, 0.2%, 40 mg/ml and 0-3 degrees C, respectively. In the microfluidization process, two important parameters, the number of cycles and the pressure were investigated systematically and 10 cycles at 23,300 psi of homogenization pressure was found to be the most efficient method. Comparing the two kinds of suspensions by TEM and particle size analysis, a small and uniform size with narrow distribution was achieved by the precipitation-combined microfluidization process. Both formulations before and after particle size reduction were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The DSC and XRD testified that there was no crystalline state changed in the size reduction process. In the in vitro dissolution test, an enhanced dissolution property was shown due to the increased surface area. Besides, lyophilization of DDB nanosuspensions was an effective measure to stabilize the systems for long time.