多西他赛脂肪乳的研究
发布时间：2018-08-29 10:59
【摘要】：目的:多西他赛是一种多西紫杉烷类抗癌药物,属于难溶性药物,目前上市剂型仅有注射剂,经过处方调研,上市产品均通过吐温80、乙醇等增溶剂的联合使用达到增溶效果,本文采用脂肪乳作为载体,提高多西他赛的溶解性,并对其进行冻干工艺研究,以期制成更加安全、有效的给药系统。方法:通过文献调研及处方前研究确定多西他赛相关理化性质,为后续处方工艺研究及储存条件提供依据。通过单因素考察,星点设计效应面法优化,筛选最优处方工艺,并进行灭菌可行性研究。通过对预冻温度,一次干燥、二次干燥工艺考察,预冻过程中退火技术的应用,确定冻干工艺,制备冻干乳。结果:1、通过处方前研究,建立了多西他赛体外分析方法,经方法学初步验证,符合检测要求。强降解实验结果表明:多西他赛在几种条件下稳定性顺序为:光照氧化高温强酸强碱。溶解度实验表示:多西他赛在含有soybean oil/MCT 1:4油相中溶解度为2.31 mg/g。2、本文通过处方工艺筛选及优化,多西他赛最优处方工艺为:按质量百分比,水相组成为0.35%泊洛沙姆188加注射用水至全量;油相组成为多西他赛1%、大豆磷脂1.0%、soybean oil 2.0%和MCT 8.0%;初乳制备时水相油相温度均为60℃;均质前调pH值5.0左右;初乳制备高剪切速度8.0×103 r/min,高剪切时间为10 min,均质压力为10000 psi,均质次数为3次。进行灭菌工艺可行性研究考察,最终采用高压均质技术与冷冻干燥技术结合,采用10%蔗糖作为冻干保护剂,进行预冻温度、时间、一次干燥、二次干燥温度时间考察,并采用退火工艺,制备冻干乳剂,复溶后粒径变化较小,均在180 nm范围内,其不会引起血管栓塞。结论:采用脂肪乳剂作为载体,可以在一定程度上提高多西他赛溶解性,并避免有机溶剂的加入,减少对人体的刺激性;为难溶性药物的开发提供新的方向与可能,但仍需后续进行更全面考察。
[Abstract]:Objective: docetaxel is a kind of docetaxel anticancer drug, which belongs to insoluble drug. At present, only the injection is available on the market. After prescription investigation, all the products on the market are solubilized by the combined use of Tween 80, ethanol and other solvents. In this paper, fat milk was used as carrier to improve the solubility of docetaxel, and the freeze-drying process was studied in order to make a more safe and effective drug delivery system. Methods: the physicochemical properties of docetaxel were determined by literature investigation and pre-prescription study, which provided the basis for further study of prescription technology and storage conditions. Through single factor investigation, the star design effect surface method was optimized, the optimum prescription technology was screened, and the feasibility of sterilization was studied. Through the investigation of pre-freezing temperature, primary drying, secondary drying process and the application of annealing technology in the pre-freezing process, the freeze-drying process was determined and the freeze-dried milk was prepared. Results: by pre-prescription study, a method of in vitro analysis of docetaxel was established. The results of strong degradation experiment showed that the stability of docetaxel under several conditions was as follows: oxidation of high temperature and strong acid and strong base by light. Solubility experiment shows that the solubility of docetaxel in the oil phase containing soybean oil/MCT 1:4 is 2.31 mg/g.2,. The optimum formulation process of docetaxel is as follows: percent by mass. The composition of water phase is 0.35% Poloxamer 188 plus injection water, the oil phase is docetaxel 1, soybean phospholipids 1.0% soybean bean oil 2.0% and MCT 8.0%, the oil phase temperature of water phase is 60 鈩，
本文编号：2210999
[Abstract]:Objective: docetaxel is a kind of docetaxel anticancer drug, which belongs to insoluble drug. At present, only the injection is available on the market. After prescription investigation, all the products on the market are solubilized by the combined use of Tween 80, ethanol and other solvents. In this paper, fat milk was used as carrier to improve the solubility of docetaxel, and the freeze-drying process was studied in order to make a more safe and effective drug delivery system. Methods: the physicochemical properties of docetaxel were determined by literature investigation and pre-prescription study, which provided the basis for further study of prescription technology and storage conditions. Through single factor investigation, the star design effect surface method was optimized, the optimum prescription technology was screened, and the feasibility of sterilization was studied. Through the investigation of pre-freezing temperature, primary drying, secondary drying process and the application of annealing technology in the pre-freezing process, the freeze-drying process was determined and the freeze-dried milk was prepared. Results: by pre-prescription study, a method of in vitro analysis of docetaxel was established. The results of strong degradation experiment showed that the stability of docetaxel under several conditions was as follows: oxidation of high temperature and strong acid and strong base by light. Solubility experiment shows that the solubility of docetaxel in the oil phase containing soybean oil/MCT 1:4 is 2.31 mg/g.2,. The optimum formulation process of docetaxel is as follows: percent by mass. The composition of water phase is 0.35% Poloxamer 188 plus injection water, the oil phase is docetaxel 1, soybean phospholipids 1.0% soybean bean oil 2.0% and MCT 8.0%, the oil phase temperature of water phase is 60 鈩，
本文编号：2210999
本文链接：https://www.wllwen.com/yixuelunwen/yiyaoxuelunwen/2210999.html
最近更新
教材专著
