Study On The Preparation And Quality Standards Of Gastric Floating Granules Loaded Matrine

Objective:Using matrine as drug, hydroxyl-propyl methyl cellulose (HPMC), ethyl cellulose (EC) as accessories and octadecyl alcohol (OA) as a floating-assistant agent to prepare the gastric floating granules loaded matrine by a coating method, and gastric floating matrine granules were studied to provide dosage forms of matrine for the treatment of gastric tumours.the quality standards of matrine granules was established.Methods:Firstly, Using HPMC and EC as major matrix, OA was used as a floating-assistant agent.4%coating ethylcellulose (w/v) contained0.8%PEG-4000(w/v).the optimal formulation of matrine gastric floating granules was selected by the single factor design, the two main factors, floating capacity and cumulative release, were comprehensively considered.Its properties was estimated Also, floating ability and cumulative release properties of matrine from granules at simulate the Gastric fluid environments were investigated, the release mechanism in vitro was researched too.Secondly, Secondly, Using HPMC was used as a swelling agent and octadecyl alcohol (OA) was used as a floating-assistant agent.4%coating ethylcellulose (w/v) contained0.8%PEG-4000(w/v).the optimal formulation of gastric floating granules loaded matrine was selected by L9(34) orthogonal design. The two main properties of floating ability and cumulative release were comprehensively considered. Finally, the optimum accessories and formation technology of gastric floating matrine granules were determined by orthogonal experiment method and multiple guidelines grading method, the quality standards of matrine granules was established. Thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) were established to identify the matrine granules and determine the content of matrine in the granules. Based on the above results, the preliminary stability of the granules was investigated.Results:Firstly, the results indicated that the surface morphology of gastric floating matrine granules with the optimum preparation technique was regular. The best prescription by the single factor test containing1/2HPMC (w/w),10%OA(w/w),20%EC (w/w),4%coating EC(w/v) and1/6EC of coating weight gain showed acceptable results in respect to in vitro evaluations. The granules showed floating ability and sustained release effect.The release behavior followed with first-order kinetics.The release of matrine from the gastric floating matrine at simulate the Gastric fluid was analyzed by a semi-empirical equation, and the results was found that drug release mechanism was due to no-Fick diffusion.Secondly,the optimal moulding process of matrine granules determined by orthogonal test was:2/3HPMC (w/w),7%OA (w/w),4%coating ethylcellulose (w/v) contained0.8%PEG-4000(w/v), and coating weight gain approaching1/6. in the orthogonal test of gastric floating granules in vitro at simulate the Gastric fluid,2h gastric totally releases26.95%, while12h may release up to90%, And it was found the floating lag time for3s and the intragastric floating time more than8hours.refecting some certain sustained-release effect and occupated a significant floating characteristic within12h in vitro, the release behavior followed with first-order kinetics. In addition, gastric floating granules loaded matrine was identified by TLC and the content of matrine in floating granules was determined by HPLC. On this basis of controllable quality standard, the preliminary stability was fulfilled to provide a reference for accouchementing, storaging and transporting matrine granules.Conclusion:In comparison with traditional matrine preparations, the gastric floating granules showed sustained release effect and floating ability, so to extend the residence time of the drug in the Simulated Gastric Fluid. It can avoid gastrointestinal irritation.and this local therapy could improve the effect of the treatment, reducing systemic toxicity, increaseing the absorption of the drug, which indicated that the potential applications of gastric cancers. It was proved that the preparation techniques of gastric floating matrine granules is reasonable and practical, the quality of preparation is simple and controllable.The gastric floating granules loaded matrine as a targeted and sustained release delivery system in the treatment of gastric tumors.The development of this new pharmaceutical preparation would enrich gastric and make them possess a variety of research potential and application prospect on curing gastric tumours.