As one of natural flavonoids, baicalin is the main active ingredient of scutellaria.Modern pharmacological studies have confirmed that baicalin showed spectrum antibacterial, anti-inflammatory, antiallergic and antispasmodic effect.But because of its poor solubility and stability, the clinical application of baicalin and drug loading in preparations was greatly limited.Nanocrystal is a highly dispersed system fabricated by novel pharmaceutical techniques, with its particle size ranging from 10nm to 1000nm.The nanocrystal system of insoluble drug usually show higher saturation solubility and dissolution rate, and improved bioavailability as well.OBJECTIVE: To improve the solubility and dissolution rate of baicalin, nanocrystal of baicalin was prepared and evaluated in vitro.METHODS: Baicalin nanocrystal was prepared by the precipitation-ultrasonication method with lecithin as stabilizer.Nanocrystals were collected by centrifugation and freeze drying process.The formulation and process parameters were optimized by single factor experimental design.The influence of solvents, solvents ratio, high shear or sonication process, different stabilizers, process of centrifugation and freeze drying on particle size and size distribution were screened.Particle size distribution, polydisperse index (PI) and Zeta potential of nanocrystal were tested using PSS.Nicomp 380ZLS laser particle sizer.The obtained nanocrystals were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD), and investigated on morphology by TEM.The in vitro dissolution profiles of nanocyrstal suspension were compared with normal suspension by slurry method.The stability of nanocrystal suspension was further evaluated on its size distribution.RESULTS: (1) When using DMSO as solvent, the average particle size of obtained nanocrystal was (474.4 nm, PI=0.138) , which is smaller than those using PEG400, glycerol and their mixture.Therefore DMSO was chosen as the good solvent for balcailin.(2) The particle size and PI firstly decreased as the solvents ratio between balcailin-DMSO solution and purified water ranging from 1∶60 to 1∶20, but increased when the solvent ratio reached 1∶10.The size of nanocrystal was reduced to (540nm, PI=0.108) for solvent ratio 1∶20.(3) The nanocrystal obtained from sonication method showed smaller particle size (363.5nm) but higher PI (0.201) when compared with high shear method (474.4nm, PI=0.138).(4) Poloxamer 188, Tween 80, Lecithin, PVA were used as the stabilizers to avoid the increase of particle size.The results show that the obtained baicalin nanocrystals varied greatly in size when different surfactants were used.The nanocrystal size was only (307.2nm, PI=0.112) for lecithin, which was much smaller than those for Poloxamer 188, Tween 80 or PVA.(5) Aggregation of nanocrystals was found using Tween-80 as stabilizer.The nanocrystal suspension using Poloxamer 188 and PVA showed a small amount of precipitation during storage, and could be well dispersed again after slight shaking.Lecithin showed minimum size change and best stabilizing effect.(6) The nanocrystal particle size increased from (307.2nm,PI=0.112) to (1025.6nm,PI=0.341) after centrifugation, but not changed during freeze drying process.(7) Baicalin nanocrystal suspension showed better performance than normal suspension in dissolution test in vitro.CONCLUSION:The obtained baicalin nanocrystal showed controllable and even particle size, good stability and improved solubility and dissolution as well.Thus, enhanced oral bioavailability could be expected.