富马酸替诺福韦二吡呋酯片工艺及质量研究

发布时间：2018-05-23 09:13

本文选题：富马酸替诺福韦二吡呋酯片 + 处方工艺研究　；参考：《山东中医药大学》2017年硕士论文

【摘要】：富马酸替诺福韦二吡呋酯是由吉利德科学公司研发的核苷酸逆转录酶抑制剂,2001年首次在美国上市,临床主要用于治疗人类免疫缺陷病毒(HIV)感染,并可与其他抗逆转录病毒药物联用。2002年2月首次获欧盟许可本品与其他抗逆转录病毒药物联合用于经早期病毒学治疗失败的HIV-1感染者。2003年5月Gilead Sciences公司宣布,欧洲药品委员会已批准在15个欧盟成员国扩大替诺福韦酯的适应症,用于未曾接受抗逆转录病毒药物治疗的H IV感染者。2008年,获准在中国上市。至今,已有包括中国在内的100多个国家批准其用于与其他抗病毒药物合用治疗HIV,是多个治疗指南推荐使用的一线抗HIV药物。本研究在参照原研的基础上,对富马酸替诺福韦二吡呋酯的处方和制备工艺进行研究,同时,进行质量研究和稳定性考察,确定了合理的处方和可行的制备工艺,实现本品的产业化生产。研究内容包括:(1)富马酸替诺福韦二吡呋酯片的处方研究以含量、有关物质和溶出曲线为主要考察指标,先进性工艺筛选实验,在确定工艺为湿法制粒压片工艺后,又对填充剂、崩解剂、粘合剂、润滑剂等辅料的种类和用量进行筛选,并通过小试验证和中试放大研究,确定富马酸替诺福韦二吡呋酯片的处方组成。(2)富马酸替诺福韦二吡呋酯片的工艺参数研究采用常规湿法制粒压片的方法制备富马酸替诺福韦二吡呋酯片,以中间品的流动性、成形性和片剂的外观性状、崩解时限和溶出曲线为评价指标,重点研究原料药粒度及片剂硬度对制剂的影响。经三批小试和三批中试放大实验,确定富马酸替诺福韦二吡呋酯片的制备工艺。(3)富马酸替诺福韦二吡呋酯片的质量研究建立了以高效液相法检测富马酸替诺福韦二吡呋酯片含量和有关物质及溶出度的方法,并进行了相应的方法学研究,结果表明方法专属性好,灵敏、准确、可控。(4)富马酸替诺福韦二吡呋酯片的稳定性研究用确定的处方工艺制备样品,样品放置高温、高湿和光照下考察影响因素,并进行了加速和长期稳定性考察,实验结果表明,本品的外观性状、含量、有关物质、溶出度等指标在实验过程中未有明显变化,证明本研究产品稳定性良好。本研究结果表明富马酸替诺福韦二吡呋酯片处方设计合理,制备工艺可行,产品稳定性好,与原研产品质量一致,完全可替代原研产品,为富马酸替诺福韦二吡呋酯片工业化生产提供了坚实的理论和实验依据。
[Abstract]:Tenofovir Fumarate dipyrifuroxime, a nucleotide reverse transcriptase inhibitor developed by Geely Science, was first launched in the United States in 2001 and is mainly used in the treatment of HIV) infection. This product was first approved by the European Union in February 2002 for use with other antiretroviral drugs in patients with HIV-1 who failed in early virological treatment. Gilead Sciences announced in May 2003, The European Drug Commission has approved the expansion of the indications of tenofovir in 15 EU member states for HIV infected patients who have not received antiretroviral treatment. In 2008, it was approved to list in China. So far, more than 100 countries, including China, have approved its use in combination with other antiviral drugs for the treatment of HIV, which is a first-line antiviral drug recommended by many treatment guidelines. In this study, the formulation and preparation process of tenofovir dipyrifuroxime fumarate were studied on the basis of reference to the original research. At the same time, the quality study and stability investigation were carried out, and the reasonable formulation and feasible preparation technology were determined. Realize the industrialization of this product. The research contents include: (1) the formulation of tenofovir Fumarate dipyrifuroxime tablets was studied mainly by the contents, related substances and dissolution curves. The advanced technology screening experiment was carried out. After determining the technology of wet granulation and pressing tablets, the fillers were added. The kinds and dosage of disintegrant, binder, lubricant and other excipients were screened, and the results were verified by small scale test and pilot scale up. Determination of prescription composition of tenofovir dipyrifuroxime fumarate tablets. Study on the technological parameters of tenofovir Fumarate dipyrifuroxime Fumarate tablets; preparation of tenofovir dipyrifuroxime fumarate tablets by conventional wet granulation, and fluidity of the intermediate, The formability and appearance of tablets, disintegration time and dissolution curve were used as evaluation indexes. The effects of particle size and tablet hardness on the preparation were studied. After three batches of small trials and three batches of pilot-scale experiments, Determination of the preparation process of tenofovir dipyrifuroxime fumarate tablets. The quality of tenofovir Fumarate dipyrifuroxime fumarate tablets was studied. A method for the determination of the content, related substances and dissolution of tenofovir dipyrifuroxime fumarate tablets by high performance liquid chromatography was established. The results showed that the method was specific, sensitive, accurate and controllable. 4) the stability of tenofovir dipyrifuroxime fumarate tablets was studied. The influencing factors were investigated under high humidity and light, and accelerated and long-term stability were investigated. The results showed that the appearance, content, related substances and dissolution of the product did not change obviously in the course of the experiment. It is proved that the stability of the product is good. The results showed that the formulation of tenofovir fumarate dipyrifuroxime tablets was reasonable, the preparation process was feasible, the product stability was good, and the quality of the product was the same as that of the original product. It provides a solid theoretical and experimental basis for the industrial production of tenofovir Fumarate dipyrifuroxime ester tablets.
【学位授予单位】：山东中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

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