甲磺酸达比加群酯胶囊处方筛选

发布时间：2018-01-01 20:03

本文关键词：甲磺酸达比加群酯胶囊处方筛选　出处：《北京理工大学》2015年硕士论文　论文类型：学位论文

【摘要】：甲磺酸达比加群酯是国内未上市的新药,在临床上具有广泛的用途,目前用于膝关节置换术或髋关节置换手术的静脉血栓预防。然而,达比加群酯胶囊的制剂处方为丸芯比较特殊的酒石酸的多颗粒制剂,且辅料酒石酸对原料的稳定性有较大的影响,但因在体内形成酸性环境,该辅料的使用是有必要的,需要采用多颗粒技术将酒石酸与原料通过隔离层的包裹分离开,制备难度较大。本文通过对国外专利处方工艺分析及对原研产品的检验和剖析,建立了以酒石酸、阿拉伯胶、羟丙甲纤维素、羟丙纤维素(SSL)、滑石粉(1250目),羟丙甲纤维素胶囊壳等为辅料,乙醇(95%)和异丙醇为溶剂,采用离心造粒机,粉末层积法制备酒石酸丸芯,用流化床包隔离层,最后用流化床上载甲磺酸达比加群酯的制粒工艺,制备了符合质量要求的甲磺酸达比加群酯胶囊,批量为3万。与原研产品对比测定结果表明,试制品在四种介质中的溶出曲线与原研制剂相似,干燥失重及胶囊壳干燥失重等质量指标与原研产品接近,体外溶出行为、杂质谱与原研一致。符合国家药品审评中心的对甲磺酸达比加群酯胶囊的品质要求。
[Abstract]:Dabigatran etexilate mesylate is not listed on the domestic drug, is widely used in clinic, currently used for venous thrombosis of knee arthroplasty or hip replacement surgery and prevention. However, dabigatran capsule prescription for special pill core tartaric acid multi particle preparation, stability and accessories tartaric acid for raw materials have great influence, but due to the formation of acidic environment in the body, the use of the materials is necessary, need to adopt the multi particle technology will tartaric acid and raw material through the isolation layer package from preparation difficult. Based on the analysis of patent prescription abroad and in the inspection and analysis of the original research products, established by Arabia gum, tartaric acid, hydroxypropyl methyl cellulose, hydroxypropyl cellulose (SSL), talcum powder (1250 mesh), hypromellose capsule shell and other accessories (95%), ethanol and isopropanol as solvent, made by centrifugal Machine, powder laminated preparation of tartaric acid pellets, using fluidized bed granulation process package isolation layer, finally by fluidized bed on dabigatran etexilate mesylate and preparation to meet the quality requirements of dabigatran etexilate mesylate capsules, batch is 30 thousand. And the original product comparison test results show that the prototype in four a medium dissolution curve and the original formulation is similar to that of dry weight and dry weight loss capsule shell quality indicators and the original product close to the in vitro dissolution behavior, consistent with the original research. The impurity profiling conforms to the National Center for drug evaluation of dabigatran mesylate group quality ester capsule requirements.

【学位授予单位】：北京理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R927.1

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