The Preparation Of Bioadhesive Sustained-release Tablet Of Total Puerariae Flavones And Its Evalution In Vivo And In Vitro

OBJECTIVE: To establish a purify technical process for Radix Puerariae total flavones; To optimize prescription of Total Puerariae Flavones (TPF) Bioadhesive Sustained-release Tablets and Studies on the main Effect Factors of Dissolution Rate in Vitro; CD To improve bioavailability of TPF by using bioadhesive tecnology;To study bioadhesive sustained-release tablets' bioadhesive strength to animal gastria and small intestine. To reserch the pharmercokinetics property and relative bioavailability of TPF bioadhesive sustained-release tablets.METHODS: D10, D201 and AB-8 type of macroreticular adsorbents were used to separate and purify total flavones,and were compared on the adsorption ratio, the elution ratio , product purity and yield. CD Using Hydroxypropyl Methl Cellulose(HPMC) , Carbopol(CP934NP) as bioadhensive matric materials , lactose as diluents and Polyvinyl PyiTolidone(PVP) as binders;Uniform Design and muli-unit regression method were applied to optimize prescription of TPF bioadhesive sustained-release tablets while dissolution, bioadhesive strenth and producing process were used as accessing index; Basket method was applied to determination the dissolution while 0.1mol.L^'HCL was used as dissolution medium(completely dissolution in 0.lmol.L/'HCL was controlled to about 12h),rotational speed was l00r.min"1 when determinating dissolution rate; A new apparatus made by ourselives were used to study the adhesive strength of sustained-release tablets in rabbits' intestine; TPF bioadhesive sustained-release tablets and common tablets were given to sixhealthy dogs in a oral single dose of 600 mg. Puerarin in dog plasma was determinated by the solid phase extract(SPE) -HPLC method. The mobile phase consisted of acetonitrile and 0.0075 mol.L'1 phosphate buffer(pH2.7)(10:90), the eluate was monitored at 248 nm , puerarin was determinated in external standard method. Pharmacokinetic calculations were carried out by 3p87 software. Statistical moment was also used in calculation of pharmacokinetic parameter.RESULTS: The static adsorption capacity of the three type of macroreticular adsorbents were 113.5mg.g¹ 133.1mg.g"1and 133.9mg.g¹ respectively; the static elution ratio were 75.6%, 66.7% and 94.2% respectively; the moveable adsorption capacity of AB-8 type was 82.0mg.g ',and the adsorption ratio was more than 85% after repeating use 11 cycles, ammount of HPMC, CP and Lactose, pH of medium , partiles have effect on the dissolution,and the uniform design tells that HPMC > CP are two main factors that effect on dissolution and bioadhesion (.P<0.05) ;Uniform design and muti-unit regression method can be used to optimize the formulation of TPF bioadhesive sustained-release tablets,and the dissolution rate in vitro of the sustained-release tablets conform to single-index model.; The strength of was stronger than non-bioadhesive tablets,aimnount of HPMC , CP and Lactose, pH of medium , partiles haw effection on dissolutin of this tablet.;0The standerd curve of puerarin was linear within the range of 17.5 ng.mL'1 to 2200ng.mL^l, the recoveries of puerarin were 85.0%¹17.1%( RSD < 8.7%) and 85.2 102.9%( RSD < 11.6%) within and between days respectively. The plasma drug concentration-time course in dogs after a oral single dose of 600 mg conformed to the one-compartment model. The AUC012 and AUC0o of common tablets * AUC012 and AUC0_of bioadhesive sustained-release tablets were 4430 + 998, 4622 + 983 and 6459 + 738, 7511 + 1026ng -h/mL respectively, Cmax were 1241 + 247 and 1040 +134 tig /mL, Tmaxwere 2.25 +0.61 and 3.83 + 0.75h respectively.The relative bioavailability of TPF bioadhesive sustained-release tablets were 151.4 + 37.6% compared with the common tablets. Results from statistics showed that there were significantdifference between bioadhesive sustained-release tablets and the common tablets in AUC0₂ AUCV, Cmax and Tmax. The bioadhesive sustained-release tablets and the common tablets were not bioequivalent. Correlation analysis showed that there was no correlation between absorption in v...