Pueraria Lobata Flavone Gastrointestinal Bioadhesive Formulations

The thesis studied the basic physicochemical character of puerariae flavones, and then studied the absorption properties of puerariae flavones by HPLC using the in situ perfusion method in rats. Using the chitosan as the absorption enhancer and bioadhesive material, and using the water or 0.1mol/L HC1 first then changing into pH6.8 buffer two hours later as the release mediator, the puerariae flavones gastrointestinal bioadhesive drug delivery systems was prepared, whose oral bioavailability was studied in beagle dogs.Firstly, the value of solubility and P_app of puerariae flavones was studies by HPLC and UV. It is found that the puerariae flavones and puerarin both have good solubility. The value of logPapp of puerarin of puerariae flavones is less than zero, which indicates that the puerarin has large polarity and poor permeability, which may causes the poor bioavailability of Puerariae flavones.Secondly, the absorption properties of puerariae flavones were studied by HPLC using the in situ perfusion method in rats. It showed that the descent of concentration of drugs is linear with circulating time, the absorption of puerariae flavones compiled with the first order kinetics; the amount of absorption is linear with the concentration of drugs, and the absorption constant and absorption percentage remained basically unchanged, which showed that the absorption of puerariae flavones is via passive transport mechanism. Meanwhile, according to statistic analysis, the uptake of puerariae flavones was different at various gastrointestinal segments, the absorption in the duodenum is better than other segments.Using the water or 0.1mol/L HCl first then changing into pH6.8 buffer two hours later as the release mediator, and using the chitosan as the absorption enhancer and bioadhesive material, the puerariae flavones gastrointestinal bioadhesive tablets are prepared through the uniform test. The test of release degree of both formulations can meet the requirement of sustained release preparation in Chinese pharmacopeia 2000. The bioadhesive force of both formulations is up to requirement by the test of self-made bioadhesive force test equipment. At last, the bioavailability of bioadhesive tablets was evaluated in vivo .In the experiment, three beagle dogs were orally administered Yufengningxin Tablets, self-made normal tablets or bioadhesive tablets. The Yufengningxin Tablets and self-made normal tablets were reference formulations and the bioadhesive tablets were tested formulations. The plasma concentration-time profiles and bioavailability of puerarin was studied and assayed by HPLC. The result indicated that Comparing to the Yufengningxin Tablets, the relative bioavailability of bioadhesive tablets(using the water as the release mediator) was 102.3%, the relative bioavailability of bioadhesive tablets(using the 0.1mol/L HCl first then changing into pH6.8 buffer two hours later as the release mediator) was 103.6%; Comparing to the self-made normal Tablets, the relative bioavailability of bioadhesive tablets(using the water as the release mediator) was 103.9%, and the relative bioavailability of bioadhesive tablets(using the 0.1mol/L HCl first then changing into pH6.8 buffer two hours later as the release mediator) was 105.3%.