本文選題：膠囊劑 + 處方篩選　； 參考：《華僑大學》2017年碩士論文

【摘要】：LY989膠囊主要用于治療雌激素受體陽性晚期乳腺癌的治療。在參考國外原研制劑的基礎上,根據(jù)國內(nèi)市場需要,對其進行仿制研究,研制了與參比制劑體外溶出行為相似的LY989膠囊。建立了紫外分光光度法測定LY989膠囊的溶出度,并對其進行方法學考察。試驗結果表明:在4.016~29.116μg/mL范圍內(nèi),LY989的濃度和吸光度線性關系良好(r=0.9996);回收率均在98%~102%范圍內(nèi),精密度試驗的RSD2%,表明該方法簡單、迅捷、專屬性好。同時對原研制劑在四種溶出介質中溶出情況進行了考察,制劑的制備工藝最終確定為干法制粒。參照原研制劑的輔料種類,選擇乳糖和微晶纖維素作為稀釋劑,二氧化硅作為助流劑,硬脂酸鎂作為潤滑劑,羧甲基淀粉鈉作為崩解劑。采用單因素試驗,從處方因素和工藝因素方面考察了各種因素對LY989膠囊體外溶出的影響。同時,使用正交試驗獲得了最優(yōu)處方。而且,按照最優(yōu)處方制備了三批樣品,進行處方驗證。結果表明自制品和原研制劑的體外溶出情況基本一致,重現(xiàn)性良好�？疾炝俗灾破泛驮兄苿┰谒姆N溶出介質(0.1 mol/L鹽酸溶液、pH4.5的醋酸鹽緩沖溶液、pH6.8的磷酸鹽緩沖溶液、水)中的溶出曲線,并采取相似因子(?2)法對其進行相似性判定,結果顯示自制品的體外溶出行為和原研制劑的相似,具有一致性。并且考察了同一批樣品溶出的均一性和多批樣品之間溶出的重復性,結果顯示自制品溶出的均一性和重復性良好。對膠囊劑進行了性狀、鑒別、裝量差異檢查、溶出度檢查、含量測定等項目的質量標準初步研究。結果表明:LY989膠囊劑的內(nèi)容物為淡黃色的粉末或顆粒,可以使用紫外分光光度法和高效液相色譜法對其進行鑒別,裝量差異檢查結果符合2015年版《中國藥典》對膠囊劑的相應要求。建立了高效液相色譜法測定LY989膠囊的含量,而且對其進行了方法學驗證。試驗結果表明:LY989的濃度在2.5~80μg/mL范圍內(nèi)時,和峰面積的線性關系良好(r=0.9995);回收率均在98%~102%范圍內(nèi),精密度試驗的RSD2%,表明該方法迅捷、精確、專屬性好。
[Abstract]:LY989 capsule is mainly used in the treatment of estrogen receptor-positive advanced breast cancer. On the basis of reference to the original preparation abroad and according to the needs of domestic market, the LY989 capsules which are similar to those of the reference preparation in vitro were developed. The dissolution of LY989 capsules was determined by UV spectrophotometry and its methodology was investigated. The results showed that the linear relationship between the concentration and absorbance of LY989 was good in the range of 4.016 渭 g/mL and 29.116 渭 g/mL, and the recoveries were within the range of 98 ~ 102%. The precision test showed that the method was simple, rapid and specific. At the same time, the dissolution of the original preparation agent in four kinds of dissolution media was investigated, and the preparation process of the preparation was determined as dry granulation. According to the kinds of excipients of the original preparation, lactose and microcrystalline cellulose were selected as diluent, silicon dioxide as flow aids, magnesium stearate as lubricant and sodium carboxymethyl starch as disintegrating agent. The effects of various factors on the dissolution of LY989 capsules in vitro were investigated in terms of prescription factors and technological factors by single factor test. At the same time, the optimum prescription was obtained by orthogonal test. In addition, three batches of samples were prepared according to the optimal prescription, and the prescription was verified. The results showed that the dissolution in vitro of the self-made product and the original preparation was basically the same and the reproducibility was good. The dissolution curves of the self-made product and the original preparation were investigated in four kinds of dissolving media: acetic acid buffer solution (pH 4.5), acetate buffer solution (pH 6.8 phosphate buffer solution, water), and the similarity was determined by the method of similarity factor (n (2). The results showed that the in vitro dissolution behavior of the self-made products was similar to that of the original preparation. The uniformity of dissolution of the same sample and the repeatability of the dissolution between the same batch of samples were investigated. The results showed that the dissolution uniformity and repeatability of the self-made products were good. The quality standards of capsule were studied, such as character, identification, quantity difference test, dissolution test and content determination. The results showed that the contents of WLY989 capsule were yellowish powder or granules, which could be identified by UV spectrophotometry and HPLC. The results of volume difference examination were in accordance with the requirements of Chinese Pharmacopoeia 2015. High performance liquid chromatography (HPLC) was established for the determination of LY989 capsules and its methodology was validated. The experimental results show that the linear relationship between the concentration and peak area is good in the range of 2.5 渭 g/mL and 80 渭 g/mL, and the recoveries are in the range of 98% and 102%. The precision test shows that the method is fast, accurate and specific.
【學位授予單位】：華僑大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R943

【參考文獻】

相關期刊論文 前10條

1 高亞琳;楊逸雨;李靖若;;晚期乳腺癌內(nèi)分泌治療現(xiàn)狀及展望[J];中華乳腺病雜志(電子版);2016年01期

2 劉文虎;常晉霞;王仕寶;;細胞周期蛋白依賴性激酶及其抑制劑構效關系研究進展[J];國際藥學研究雜志;2014年01期

3 方瓊英;吳瓊;張秀玲;馬小麗;;乳腺癌的流行現(xiàn)狀分析[J];中國社會醫(yī)學雜志;2012年05期

4 付靜;沈中華;程飛雄;劉桂霞;李衛(wèi)華;唐峗;;芳香化酶的結構、催化機制及其抑制劑研究進展[J];藥學學報;2012年01期

5 崔中立;張沐新;楊曉虹;王廣樹;;芳香化酶抑制劑的研究進展[J];中國藥物化學雜志;2010年01期

6 吳克瑾;;乳腺癌的內(nèi)分泌治療[J];中國實用外科雜志;2009年09期

7 楊秀麗;孫進;何仲貴;;格列吡嗪油水分配系數(shù)和平衡溶解度的測定[J];中國藥劑學雜志(網(wǎng)絡版);2009年03期

8 王華慶;錢正子;;乳腺癌的內(nèi)分泌治療[J];中國實用內(nèi)科雜志;2007年24期

9 張迎輝,盧斌;他莫昔芬在乳腺癌治療中的耐藥性機制研究[J];國外醫(yī)學.藥學分冊;2002年04期

10 高春生,崔光華;水滲透對速崩制劑崩解作用的研究[J];中國藥學雜志;2000年05期

相關重要報紙文章 前1條

1 ;2015年批準上市的“重磅炸彈”藥物[N];中國醫(yī)藥報;2016年

，

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