帕博西林（palbociclib）胶囊处方及其质量的研究

发布时间：2018-02-26 23:30

  本文关键词： 帕博西林(palbociclib)胶囊 处方筛选 质量探究 稳定性探究　出处：《华东师范大学》2017年硕士论文　论文类型：学位论文

【摘要】：帕博西林(Palbociclib)是辉瑞公司研发出的一种CDK4/6抑制剂,通常用来医治女性ER阳性的乳腺癌患者。由于它在临床治疗上所表现出的突出效果,在2015年2月3日得到美国FDA的批准,同意其在美国上市,药品名字为Ibrance。且第一年的年销售额就已超过7亿美元,有着巨大的市场价值。目前它还没有在除了美国以外的其它任何国家上市过,国内外也无任何有关其制剂的报道文献。本文以上市药物Ibrance的说明书为参照,进行了其有关制剂的研究。胶囊的处方和处方工艺探究过程中,主要采用正交试验法进行处方筛选,依据原料药的理化性质初步确定处方生产工艺,再以颗粒的外观、流动性大小以及胶囊的溶出度为指标筛选好的处方,最终确定的最佳处方为(100粒):帕博西林7.5 g,微晶纤维素11 g,一水乳糖5.6 g,羧甲基淀粉钠1.59 g,胶态二氧化硅0.26 g,硬脂酸镁0.55 g。以3%羧甲基淀粉钠溶液为粘合剂湿法制粒后,60℃干燥整粒,填充胶囊。为考察处方及制备工艺的合理性和稳定性,再以最佳处方和处方工艺制备小试三批产品进行质量的测定。结果质量均符合规定。产品的质量探究主要以有关物质、含量及溶出度为检测对象,通过创建产品溶出度测定的方法以及含量和有关物质的HPLC方法对产品进行测定。而且新建的方法都经过了相应方法学的验证,验证结果表明新建立的方法符合有关方法的要求,可用于本处方及其处方工艺下胶囊质量的检测。稳定性的初步研究参照药典上的相关规定,进行了影响因素、加速和长期的实验探究,考虑在相应实验条件下产品外型、水分等检测项目的变化。结果表明产品对光较为敏感,在强光照下有关物质会增加,温度对水分的影响较大。所以,产品适宜贮存在阴凉通风和避光的环境下。在加速和长期实验中产品的外观、水分等变化不大,表明制备出的样品性质稳定。
[Abstract]:Pfizer Palbociclib, a CDK4/6 inhibitor developed by Pfizer, is commonly used to treat women with ER positive breast cancer. It was approved by FDA in the United States in February 3rd 2015 because of its outstanding clinical efficacy. Agreed to be listed in the United States, the drug is called Ibrance.And its annual sales in its first year have exceeded $700 million, which is of great market value. It has not yet been listed in any country other than the United States. There are no reports about the preparation at home and abroad. According to the specification of the listed drug Ibrance, the research on the preparation, the prescription and the prescription process of the capsule were carried out in this paper. The prescription production process was preliminarily determined according to the physical and chemical properties of the raw material, and the prescription was screened according to the appearance of the granules, the fluidity and the dissolution of the capsules. The best formulation was determined as follows: paroxicillin 7.5 g, microcrystalline cellulose 11 g, lactose monohydrate 5.6 g, sodium carboxymethyl starch 1.59 g, colloidal silica 0.26 g, magnesium stearate 0.55 g. 3% sodium carboxymethyl starch solution was used as binder. After granulation, the seeds were dried at 60 鈩，

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