Preparation And Pharmacokinetics Study Of Enteric-Coated Sustained-Release Pellets Of Total Saponins Of Panax Notoginseng Flower Buds

Objective:On the basis of the previous studies on the extraction,separation and pharmacological experiments of total saponins of Panax notoginseng flower buds?PNS?,combined with the physicochemical properties and the advantages of slow-released preparations,the total saponin enteric-release and sustained-release pellets?PNS-P?were prepared.Pharmacokinetic was studied to provide theoretical and experimental basis for the development and in vivo research of PNS in the treatment of hypertension and cardiovascular protection.Methods:?1?The best adsorpted macroporous resin of Panax notoginseng flower buds extract was screened by static adsorption and dynamic adsorption.The orthogonal experiment was carried out to screen out the best separation and purification process.?2?An in vitro quantitative method for the determination of ginsenoside Rb₁,Rb₂,Rb₃,and Rc,the active constituents of PNS was established.The physicochemical properties and preliminary stability of the purified PNS were investigated.?3?The Panax notoginseng flower buds saponins enteric-coated sustained-release pellets?PNS-P?were prepared by fluidized bed with blank pellet core method.The drug release study,the stability study and pharmaceutics investigation of PNS-P were carried out.?4?In vivo quantitative analysis method for Rb₁,Rb₂,Rb₃,and Rc was established.The pharmacokinetic study of the PNS and PNS-P was carried out.Results?1?HPD100 macroporous resin has good adsorption,and the best adsorption process is macroporous resin 1:6 aspect ratio,3 times alcohol flow rate,and 3 times alcohol dosage.The preferred process elution rate is 91.39%,the transfer rate is 90.40%,and the purity of PNS is 57.58%.?2?The established in vitro analysis method of PNFS has high sensitivity and good reproducibility,and can meet the needs of sample analysis and detection.Pre-prescription research results show that PNS are acidic,have good solubility,have a small apparent oil-water partition coefficient,have strong hygroscopicity,and are easily hydrolyzed in an acidic environment.?3?The fluidized bed blank pellet core method was used,and 0.5-0.6 mm microcrystalline cellulose was used as the blank pellet core.Lactose,which accounts for 4%of the dry weight of the polymer,acts as a porogen,100%of talc is used as an anti-adhesive agent,and 10%of Eudragit NE30D is weight-coated as a slow-release liquid coating solution.The PNS-P was prepared by coating 20%ebabad as an enteric coating,and the drug content was 37.47%.In the in vitro release test,the PNS-P were not released in gastric juice,and slowly released in intestinal fluid,and the cumulative release at 12h reached an average of 82.65%.The release of PNS-P was studied and it was found that the release mechanism of the drug was Fick diffusion.The results of the 3-month stability study showed that the appearance,fluidity,and drug release of the pellets were stable.?4?The established in vivo analytical methods for the saponins Rb₁,Rb₂,Rb₃,and Rc are fast and reproducible.Compared with PNS,the pharmacokinetic parameters t_maxMRT and t_1/2of PNS-P were prolonged,and the results were significantly different?P<0.05?.The relative bioavailability of the pellets(pellets AUC_0-?/total saponin AUC_0-?)was 96.4%for Rb₁,130.0%for Rb₂,84.5%for Rb₃,and 100.4%for Rc.The average relative bioavailability was 102.8%.Through in vivo and in vitro correlation studies,it was found that ginsenoside Rb₁ and Rb₃ had good in vitro and in vivo correlation?P<0.05?.Conclusion:Establish a sensitive and reliable method for quantitative analysis of PNS in vitro and in vivo.PNS-P have sustained release characteristics in vitro.the PNS-P were not released in gastric juice,and slowly released in intestinal fluid,and the cumulative release at 12 h reached an average of 82.65%.The study of physical and chemical properties laid a theoretical foundation for the formulation of dosage forms.The research of pharmacy and pharmacokinetics provided experimental basis for the development of new dosage forms.