本文關(guān)鍵詞： 帕博西林(palbociclib)膠囊 處方篩選 質(zhì)量探究 穩(wěn)定性探究　出處：《華東師范大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：帕博西林(Palbociclib)是輝瑞公司研發(fā)出的一種CDK4/6抑制劑,通常用來醫(yī)治女性ER陽性的乳腺癌患者。由于它在臨床治療上所表現(xiàn)出的突出效果,在2015年2月3日得到美國FDA的批準(zhǔn),同意其在美國上市,藥品名字為Ibrance。且第一年的年銷售額就已超過7億美元,有著巨大的市場價值。目前它還沒有在除了美國以外的其它任何國家上市過,國內(nèi)外也無任何有關(guān)其制劑的報道文獻(xiàn)。本文以上市藥物Ibrance的說明書為參照,進(jìn)行了其有關(guān)制劑的研究。膠囊的處方和處方工藝探究過程中,主要采用正交試驗法進(jìn)行處方篩選,依據(jù)原料藥的理化性質(zhì)初步確定處方生產(chǎn)工藝,再以顆粒的外觀、流動性大小以及膠囊的溶出度為指標(biāo)篩選好的處方,最終確定的最佳處方為(100粒):帕博西林7.5 g,微晶纖維素11 g,一水乳糖5.6 g,羧甲基淀粉鈉1.59 g,膠態(tài)二氧化硅0.26 g,硬脂酸鎂0.55 g。以3%羧甲基淀粉鈉溶液為粘合劑濕法制粒后,60℃干燥整粒,填充膠囊。為考察處方及制備工藝的合理性和穩(wěn)定性,再以最佳處方和處方工藝制備小試三批產(chǎn)品進(jìn)行質(zhì)量的測定。結(jié)果質(zhì)量均符合規(guī)定。產(chǎn)品的質(zhì)量探究主要以有關(guān)物質(zhì)、含量及溶出度為檢測對象,通過創(chuàng)建產(chǎn)品溶出度測定的方法以及含量和有關(guān)物質(zhì)的HPLC方法對產(chǎn)品進(jìn)行測定。而且新建的方法都經(jīng)過了相應(yīng)方法學(xué)的驗證,驗證結(jié)果表明新建立的方法符合有關(guān)方法的要求,可用于本處方及其處方工藝下膠囊質(zhì)量的檢測。穩(wěn)定性的初步研究參照藥典上的相關(guān)規(guī)定,進(jìn)行了影響因素、加速和長期的實驗探究,考慮在相應(yīng)實驗條件下產(chǎn)品外型、水分等檢測項目的變化。結(jié)果表明產(chǎn)品對光較為敏感,在強(qiáng)光照下有關(guān)物質(zhì)會增加,溫度對水分的影響較大。所以,產(chǎn)品適宜貯存在陰涼通風(fēng)和避光的環(huán)境下。在加速和長期實驗中產(chǎn)品的外觀、水分等變化不大,表明制備出的樣品性質(zhì)穩(wěn)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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