| Objective:Puerarin is mainly used clinically for treatment of cardiovascular system diseases. It has received wide attention for its abundant availability and good pharmacological action, which has led to extensive exploration and study.Puerarin has poor water solubility and liposolubility,and has poor bioavailability by oral administration.It is essential to improve the solubility and the bioavailability of Puerarin.ICP(Inclusion Complexes of Puerarin with Hydroxypropyl-β-cyclodextrin),SDP(Solid Dispersion of Puerarin with Polyethylene glycol 6000) and PMMP(Bile Salt/Phosphatidylcholine Mixed Micelles System of Puerarin) were prepared in order to improve its poor solution by different pharmaceutics adjuvant on the basis of the theories of clathration,solid dispersion and mixed micelles.It proved that they did improve the solubility of Puerarin significantly.The following essay will investigate the absorption characteristics of Puerarin,ICP,SDP,and PMMP by oral administration with in vitro,in situ,and in vivo methods and study the correlation of these methods.Method:(1) Investigation of oil/water apparent partition coefficient(oil/water Papp):The oil/water Papp of Puerarin,ICP,SDP,and PMMP were investigated in three media with different pH.(2) Investigation of uptaking characteristics in vitro:The apparent permeability coefficient(Papp) of Puerarin,ICP,SDP,and PMMP in Caco-2 model system were investigated.(3) Absorption in rats' stomachs and small intestines in situ:The accumulative absorption rate of Puerarin,ICP,SDP,and PMMP were investigated in rats' stomachs and small intestines in situ within 2 h and 3 h respectively.(4) Pharmacokinetics in vivo experiment in Beagle dogs:The absolute bioavailability of Puerarin,ICP,SDP,and PMMP were obtained and the pharmacokinetics parameters were calculated.(5) Pharmacokinetics in vivo experiment in rats:Distribution of Puerarin,ICP,SDP,and PMMP in rats' blood plasma and main tissues were investigated.Result:(1) The oil/water Papp of Puerarin in three media with different pH were all between 0 and 1,which suggested that Puerarin was of hydrophility.The oil/water Papp of Puerarin,ICP, SDP,and PMMP differed from each other in three media.(2) In Caco-2 cell in vitro,the Papp of Puerarin,ICP,SDP,and PMMP from BL to AP all surpassed the Papp from AP to BL.The transport rate from AP to BL was PMMP＞SDP＞Puerarin＞ICE(3) The 2 h accumulative absorption rate in rats' stomachs in situ were Puerarin 23.52%,PMMP 13.77%,SDP 9.26%, ICP 7.45%.The 3 h accumulative absorption rate in rats' small intestines in situ were Puerarin 20.77%,ICP 15.82%,SDP 13.09%.(4) After a single dose of Puerarin by intravenous injection in Beagle dogs,the blood concentration-time curve was shown to fit a two-compartment model while a one-compartment model after a single dose of Puerarin, ICP,SDP,and PMMP by oral administration.The absolute bioavailability were PMMP 32.04%,Puerarin 6.40%,SDP 4.53%,ICP 2.00%.(5) After a single dose by oral administration of Puerarin,ICP,SDP,and PMMP in rats,the concentration of Puerarin was determined by HPLC in the main tissues such as liver,heart,spleen,lung,kidney and brain after a certain time.The concentration in each tissue after a single dose of PMMP was remarkably higher than that of Puerarin.Conclusion:After PMMP was prepared,the absorption of Puerarin by oral administration was improved significantly,while after ICP and SDP were prepared,the absorption of Puerarin by oral administration was not improved.There was good correlation among the methods of in vitro,in situ,and in vivo. |
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