Characterization and evaluation in vivo of baicalin-nanocrystals prepared by an ultrasonic-homogenization-fluid bed drying method

AIM:To improve the absorption and bioavailability of baicalin using a nanocrystal(or nanosuspension) drug delivery system.METHODS:A tandem,ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders,and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy,photon correlation spectroscopy,powder X-ray diffraction,physical stability,and solubility experiments.Furthermore,in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo.RESULTS:The mean particle size of baicalin-nanocrystals was 236 nm,with a polydispersity index of 0.173,and a zeta potential value of-34.8 mV,which provided a guarantee for the stability of the reconstituted nanosuspension.X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process.Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable.It was shown that the solubility of baicalin in the form of nanocrystals,at 495 gmL-1,was much higher than the baicalin-microcrystals and the physical mixture(135 and 86.4 gmL-1,respectively).In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations.In addition,after oral administration to rats,the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability(with the AUC(0-t) value of 206.9621.23 and 127.9514.41 mgL-1h-1,respectively).CONCLUSION:The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin,compared with pure baicalin coarse powder and micronized baicalin.