The Preparation Of Apigenin Nanosuspension And Its Pharmacokinetic Studies

[Object] Apigenin is insoluble in water but also insoluble in organic solvents drug establish their HPLC detection methods; and be prepared with a high concentration of nano-suspensions, the best prescription lyophilization process research and study particle size, drug loading, morphology and stability; investigate the influence of different media release its release characteristics; research apigenin nanosuspension in pharmacokinetic properties in rats, and calculate the relevant parameters.[Method] In this paper, efficient chromatography analysis methods established apigenin; precipitation method using micro-ultrasound apigenin nanosuspension to particle size and distribution of the indexes on the formulation and preparation process optimization, to determine the best preparation; By Zetasizer Nano-ZS90 detect nanometer particle size analyzer, drawn apigenin nanosuspension particle size and its distribution; with TEM apigenin nanosuspension of morphology; apigenin nanosuspension will stand at room temperature save, respectively, in place one day, 3 days,7 days,14 days,31 days after the sampling, inspection of its drug content and particle size changes; Apigenin nanosuspension for different concentrations for different types of lyoprotectants lyophilized preparation, and then reconstituted by Zetasizer Nano-ZS90 nanoparticle size analyzer measured the particle size, filter out the best lyophilized formulation; By dialysis, respectively, were 0.5 h,1 h,2 h,4 h,6 h,8 h,12 h,24 h,36 h,48 h,60 h,72 h to take point, examine apigenin nano suspensions in different release media (1% SDS in PBS,2% SDS in PBS,20% ethanol in PBS) release profile; Rats were injected intravenously nanosuspension apigenin and apigenin crude suspension (40 μg · g-1). After separately at different time points orbital venous plexus puncture blood plasma was measured by HPLC plasma concentration, and with the blood concentration DAS2.0 software for processing.[Results] Using micro-ultrasound precipitation apigenin nanosuspension Prepared opalescent yellowish transparent by Zetasizer Nano-ZS90 nanometer particle size analyzer test results, the diameter of 83.39 nm, polydispersity index (PDI) of 0.25, the potential is-19 mv; By observing the results of a transmission microscope, apigenin nanosuspension for similar spherical crystals evenly distributed; nano-suspensions prepared in accordance with the best prescription, the drug loading was 4.44 ± 0.06%; lyoprotectant optimal prescription screening result was 1% trehalose reconstituted lyophilized best case; Apigenin nanosuspension release results showed that in 20% EtOH/PBS (phosphate buffer, PH= 7.4) in 72 hours to reach the 80% cumulative release, Higuchi equation y= 10.404x-7.8105, R2= 0.9919; Pharmacokinetic results indicate that, AUCO-∞ increased by 7.14 times, MRT (0-∞) increased 6.15-fold, Cmax increased 17.78 times. Apigenin nanosuspensions relative bioavailability increase 7.14 times, significantly increases the absorption of the drug.[Conclusion] Preparation of apigenin nanosuspension (Ap-Nps) simple, have a high drug loading,a good sustained release in vitro release. Apigenin nanosuspension relative bioavailability increase 7.14 times, in vivo has obviously slow release effect.