Preparation And Evaluation Of Total Triterpene Of Paliurus Ramosissimus Solid Dispersion

The total triterpene of Paliurus Ramosissimus(TTPR)is a generic term for triterpenoids extracted from fresh leaves of the genus Paliurus ramosissimus(Lour.),which is the main activity of fresh leaves of Paliurus.The previous study of the research team found that these components have a good inhibitory effect on a variety of malignant tumor cells.However,TTPR is poorly water-soluble,affecting its absorption and excretion in the gastrointestinal tract,resulting in low bioavailability in vivo,which greatly affects its efficacy in vivo.Therefore,solid dispersion technology is used to improve the solubility of TTPR.In turn,the bioavailability of TTPR in vivo is improved.In this study,firstly,we established a method for the determination of paliurusene and betulinic acid in a solid dispersion and through methodological investigation,it shows that the method is simple,stable and reliable.Secondly,five kinds of water-soluble carrier materials and two methods were used to prepare solid dispersion,by examining these factors that preparation method,carrier material,drug to carrier ratio,solvent type and temperature to select the best preparation process.The results showed that dissolution and solubility of paliurusene and betulinic acid were increased when PVPK30 was used as the carrier and anhydrous ethanol was used as the solvent,the drug loading ratio was 1:5,the magnetic stirring temperature was 80 ?,and the solid dispersion prepared by the solvent method.Secondly,Fourier transform infrared spectroscopy(FT-IR),scanning electron microscopy(SEM)and X-ray diffraction(XRD)were used to identify whether the solid dispersion is formed,and the results indicate that the TTPR is bound to the carrier in the form of a hydrogen bond and is distributed in the carrier in an amorphous state;Through inhibition experiments of AGS cells,NCI-N87 and HGC-27,it was found that the inhibition rate of TTPR solid dispersion on cells was higher than TTPR and it is speculated that due to the action of the carrier,the wettability of TTPR is enhanced,the solubility is improved,and the permeability to cells is enhanced,thereby increasing the inhibition rate of the drug against cancer cells.we established a method for determination of paliurusene and betulinic acid in rat gastric juice and intestinal juice.The rat model of gastrointestinal perfusion was established to study the absorption of TTPR and solid dispersion in the gastrointestinal tract of rats.The results showed that the absorption rate of betulinic acid and paliurusene in the TTPR solid dispersion was higher than TTPR in the stomach.For intestinal absorption,the absorption rate constant of the TTPR solid dispersion was higher than TTPR at the same concentration,and the same absorption site,indicating that the solid dispersion technique improved the absorption of TTPR in the gastrointestinal tract.Powder,stability and accelerated test studies on the TTPR solid dispersion showed that the fluidity of the TTPR solid dispersion was improved compared to TTPR.Through stability studies,it was found that the TTPR solid dispersion was stable under high temperature conditions(60 ° C),and the properties of the solid dispersion changed under high humidity(75% RH)and strong light(4000 lx ± 500 lx),and the index The dissolution rate of the content of the component is lowered,suggesting that the solid dispersion should be stored in the dark and protected by accelerated test.The accelerated test shows that the TTPR solid dispersion can be stabilized at a temperature of 40 ° C and a humidity of 75% after being sealed with aluminum foil.Months.