| Objective:Preparation of controlled-release Xiaoke osmotic pump tablets and studies on drug release mechanism.Xiaoke osmotic pump tablets are improved based on the Xiaoke Pills group,which has a rapid onset of action,a definite curative effect of chemical drugs,and a synergistic hypoglycemic effect of Chinese herbs.The dual role of conditioning and synergism and attenuating toxicity will be achieved.In order to modernize Xiaoke Pills,the traditional pill was changed to osmotic pump tablets,and its quality testing methods,pharmacokinetics,and pharmacodynamics were studied.Method:The cellulase enzymatic method was used to extract puerarin and other active ingredients.In response to single factor experiments,cellulase enzyme concentration,extract pH value,extraction temperature,feed liquid mass concentration and other factors on the extraction rate of puerarin were used.The facial method further optimized the extraction process of Radix Puerariae in Xiaoke Tablets and obtained the best extraction technological conditions.The drug-containing layer prescription,push layer prescription,coating prescription and tableting process were studied to prepare a Xiaoke osmotic pump;the release behavior of osmotic pump tablets was investigated,and the release control mechanism of glibenclamide was studied.A method for the determination of puerarin,astragaloside and glibenclamide in Xiaoke osmotic pump tablets was established using HPLC method.The quantitative analysis method of plasma glibenclamide was established after oral administration of Xiaoke osmotic pump in rabbits by HPLC method.The concentration of drug in plasma was determined and the relevant pharmacokinetic parameters were calculated.To observe the changes of fasting blood glucose and glucose load after oral administration of Xiaoke osmotic pump tablet in rats.Result:The response surface methodology was further used to optimize the extraction technological parameters.optimum extraction condition was as follow:extraction temperature 50 ?,pH value of extraction solution 3.9,the ratio of material to solvent 15mg/mL,cellulose concentration 3.6 mg/mL.Under the optimized extraction condition,the extraction rate of puerarin was determined to be 9.5%by high-performance liquid chromatography,which was significantly higher than that by traditional water extraction method and acid extraction method(P<0.01).In the dissolution test,it was found that lupeol pellets exhibited a controlled release effect.The drug release of the glibenclamide controlled-release pellets was characterized of various media including pH 2.0,pH 4.5 and purified water.The results indicated that drug release profiles they had the excellent zero-order release profile in different media evaluation in vitro.The test formulation was shown to have delayed-release property with extended-release in vivo.The results of pharmacodynamics experiments on the effect of rat blood glucose on the blood glucose showed that the Xiaoke osmotic pump tablet could significantly inhibit the increase of blood glucose after the sugar loading of animals,and its effect had a significant dose relationship.Xiaoke osmotic pump tablets make normal rats fasting glucose levels have fallen and disappeared in 2 h compared with the insulin.Xiaoke osmotic pump tablets does not cause hypoglycemia that it is suitable for patients with type 2 diabetes uncontrol blood sugar.Compared with the insulin treatment Xiaoke osmotic pump tablets without side effects of hypoglycaemia.Hypoglycemic effect is safe and effective.Animal experimental results show that using Xiaoke osmotic pump tablets 24-hour blood sugar levels steady.Conclusion:the experimentally determined extraction method has high extraction efficiency,and the quality control method is convenient and feasible,and can well control the quality of the preparation.Xiaoke osmotic pump tablets can lower blood glucose,inhibit blood sugar elevation after sugar load.It can effectively and safely achieve the ideal therapy target for mellitus and possess favorable application perspective. |
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