【作者】 刘怡；

【导师】 张丽男； 刘洋； Niu Feng；

【作者基本信息】 河北科技大学 ， 药学（专业学位）， 2018， 硕士

【摘要】 阿托伐他汀钙片是一类畅销的治疗高脂血症的药物,是一种3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂。目前高脂血症已逐渐成为危害人类生命的第一隐形杀手。阿托伐他汀钙片的研究对患者、家庭以及社会都有十分重要的意义。能否制备与原研产品稳定性一致、溶出行为相似的阿托伐他汀钙片剂是本课题的关键。本课题首先参照原研处方进行了处方筛选,初步确定了辅料组成及用量。确定的处方组成为:主药为7%、微晶纤维素PH101为28%、乳糖为21.6%、碳酸钙为29%、低取代羟丙纤维素为7%、交联羧甲基纤维素钠为6.4%、硬脂酸镁为1%、薄膜衣为1.5%~3.0%。通过对制备工艺的考察,确定了制粒工艺参数、压片工艺参数以及包衣工艺参数。采用确定的处方工艺制备了三批小试样品并进行了验证,三批小试样品的溶出度、含量及含量均匀度均符合要求,且有关物质增长趋势与原研相似。建立了本品的质量标准,设定了性状、鉴别、溶出度、含量均匀度、有关物质含量等检测项目,建立了高效液相色谱法测定阿托伐他汀钙片有关物质的色谱条件,结果表明:该方法专属性、精密度良好,准确度高,耐用性良好。含量测定色谱条件同有关物质,试验结果表明该方法专属性、精密度良好,准确度高,耐用性良好,建立了紫外分光光度法检测阿托伐他汀钙片的溶出度和含量均匀度,并进行了方法学验证。阿托伐他汀钙片稳定性实验结果表明,在影响因素、加速条件和长期条件下,自制样品与原研药品的性状、含量、有关物质、溶出度变化趋势基本一致。具有较好的稳定性。制定的阿托伐他汀钙片的质量标准科学、可靠。更多还原

【Abstract】 Atorvastatin calcium tablet is a type of best-selling anti-hyperlipidemia drug,and also is a reductase inhibitor for 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA).At present,hyperlipidemia has gradually become the most invisible killer endangering human life.The research on atorvastatin calcium tablets is of great significance to patients,families and society.The key to this issue is whether atorvastatin calcium tablets with similar stability and original dissolution behavior can be prepared.This topic firstly carried out a prescription screening with reference to the original research prescription,and initially determined the composition and dosage of excipients.The prescription was composed of 7% of the main drug,28% of microcrystalline cellulose PH101,21.6% of lactose,29% of calcium carbonate,7% of low-substituted hydroxypropyl cellulose,and 6.4% of croscarmellose sodium,1% of magnesium stearate,and 1.5% to 3.0% of film clothing.Through the inspection of the preparation process,the granulation process parameters,the tableting process parameters and the coating process parameters were determined.Three batches of small test samples were prepared using the established prescription process and small test certificates were made.The dissolution,content and uniformity of the three batches of small test samples all met the requirements,and the growth trend of the related substances was similar to that of the original study.The quality standards for this product were established,and the items such as traits,identification,dissolution,content uniformity,and related substance content were set up.The chromatographic conditions for the determination of atorvastatin calcium tablet-related substances were established by HPLC.The results show that this method has good specificity,precision,high accuracy and good durability.Therefore,this method can effectively control the related substances of this product.The chromatographic conditions of the content determination are the same as those of the related substances.The test results show that the method has good specificity,precision,high accuracy,good durability.Ultraviolet spectrophotometry was used to detect the dissolution and content uniformity of atorvastatin calcium tablets.The stability of atorvastatin calcium tablets showed that under the influence of factors,accelerated conditions and long-term conditions,the self-made samples and the original research drugs were basically the same in terms of their traits,content,relate substances,and dissolution rate.And the atorvastatin calcium tablets have better stability.The quality standards developed for atorvastatin calcium tablets are of scientific,reliable.更多还原