小分子抗癌药LY989的制剂学研究

发布时间：2018-06-04 06:01

本文选题：胶囊剂 + 处方筛选　；参考：《华侨大学》2017年硕士论文

【摘要】：LY989胶囊主要用于治疗雌激素受体阳性晚期乳腺癌的治疗。在参考国外原研制剂的基础上,根据国内市场需要,对其进行仿制研究,研制了与参比制剂体外溶出行为相似的LY989胶囊。建立了紫外分光光度法测定LY989胶囊的溶出度,并对其进行方法学考察。试验结果表明:在4.016~29.116μg/mL范围内,LY989的浓度和吸光度线性关系良好(r=0.9996);回收率均在98%~102%范围内,精密度试验的RSD2%,表明该方法简单、迅捷、专属性好。同时对原研制剂在四种溶出介质中溶出情况进行了考察,制剂的制备工艺最终确定为干法制粒。参照原研制剂的辅料种类,选择乳糖和微晶纤维素作为稀释剂,二氧化硅作为助流剂,硬脂酸镁作为润滑剂,羧甲基淀粉钠作为崩解剂。采用单因素试验,从处方因素和工艺因素方面考察了各种因素对LY989胶囊体外溶出的影响。同时,使用正交试验获得了最优处方。而且,按照最优处方制备了三批样品,进行处方验证。结果表明自制品和原研制剂的体外溶出情况基本一致,重现性良好。考察了自制品和原研制剂在四种溶出介质(0.1 mol/L盐酸溶液、pH4.5的醋酸盐缓冲溶液、pH6.8的磷酸盐缓冲溶液、水)中的溶出曲线,并采取相似因子(?2)法对其进行相似性判定,结果显示自制品的体外溶出行为和原研制剂的相似,具有一致性。并且考察了同一批样品溶出的均一性和多批样品之间溶出的重复性,结果显示自制品溶出的均一性和重复性良好。对胶囊剂进行了性状、鉴别、装量差异检查、溶出度检查、含量测定等项目的质量标准初步研究。结果表明:LY989胶囊剂的内容物为淡黄色的粉末或颗粒,可以使用紫外分光光度法和高效液相色谱法对其进行鉴别,装量差异检查结果符合2015年版《中国药典》对胶囊剂的相应要求。建立了高效液相色谱法测定LY989胶囊的含量,而且对其进行了方法学验证。试验结果表明:LY989的浓度在2.5~80μg/mL范围内时,和峰面积的线性关系良好(r=0.9995);回收率均在98%~102%范围内,精密度试验的RSD2%,表明该方法迅捷、精确、专属性好。
[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.
【学位授予单位】：华侨大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

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