本文選題：富馬酸替諾福韋二吡呋酯片 + 處方工藝研究��； 參考：《山東中醫(yī)藥大學》2017年碩士論文

【摘要】：富馬酸替諾福韋二吡呋酯是由吉利德科學公司研發(fā)的核苷酸逆轉錄酶抑制劑,2001年首次在美國上市,臨床主要用于治療人類免疫缺陷病毒(HIV)感染,并可與其他抗逆轉錄病毒藥物聯(lián)用。2002年2月首次獲歐盟許可本品與其他抗逆轉錄病毒藥物聯(lián)合用于經(jīng)早期病毒學治療失敗的HIV-1感染者。2003年5月Gilead Sciences公司宣布,歐洲藥品委員會已批準在15個歐盟成員國擴大替諾福韋酯的適應癥,用于未曾接受抗逆轉錄病毒藥物治療的H IV感染者。2008年,獲準在中國上市。至今,已有包括中國在內的100多個國家批準其用于與其他抗病毒藥物合用治療HIV,是多個治療指南推薦使用的一線抗HIV藥物。本研究在參照原研的基礎上,對富馬酸替諾福韋二吡呋酯的處方和制備工藝進行研究,同時,進行質量研究和穩(wěn)定性考察,確定了合理的處方和可行的制備工藝,實現(xiàn)本品的產(chǎn)業(yè)化生產(chǎn)。研究內容包括:(1)富馬酸替諾福韋二吡呋酯片的處方研究以含量、有關物質和溶出曲線為主要考察指標,先進性工藝篩選實驗,在確定工藝為濕法制粒壓片工藝后,又對填充劑、崩解劑、粘合劑、潤滑劑等輔料的種類和用量進行篩選,并通過小試驗證和中試放大研究,確定富馬酸替諾福韋二吡呋酯片的處方組成。(2)富馬酸替諾福韋二吡呋酯片的工藝參數(shù)研究采用常規(guī)濕法制粒壓片的方法制備富馬酸替諾福韋二吡呋酯片,以中間品的流動性、成形性和片劑的外觀性狀、崩解時限和溶出曲線為評價指標,重點研究原料藥粒度及片劑硬度對制劑的影響。經(jīng)三批小試和三批中試放大實驗,確定富馬酸替諾福韋二吡呋酯片的制備工藝。(3)富馬酸替諾福韋二吡呋酯片的質量研究建立了以高效液相法檢測富馬酸替諾福韋二吡呋酯片含量和有關物質及溶出度的方法,并進行了相應的方法學研究,結果表明方法專屬性好,靈敏、準確、可控。(4)富馬酸替諾福韋二吡呋酯片的穩(wěn)定性研究用確定的處方工藝制備樣品,樣品放置高溫、高濕和光照下考察影響因素,并進行了加速和長期穩(wěn)定性考察,實驗結果表明,本品的外觀性狀、含量、有關物質、溶出度等指標在實驗過程中未有明顯變化,證明本研究產(chǎn)品穩(wěn)定性良好。本研究結果表明富馬酸替諾福韋二吡呋酯片處方設計合理,制備工藝可行,產(chǎn)品穩(wěn)定性好,與原研產(chǎn)品質量一致,完全可替代原研產(chǎn)品,為富馬酸替諾福韋二吡呋酯片工業(yè)化生產(chǎn)提供了堅實的理論和實驗依據(jù)。
[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.
【學位授予單位】：山東中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R943

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