盐酸度洛西汀肠溶片剂的研究

发布时间：2018-03-01 08:21

  本文关键词： 盐酸度洛西汀 肠溶片 制备研究 质量分析 抗抑郁　出处：《河北科技大学》2017年硕士论文　论文类型：学位论文

【摘要】：盐酸度洛西汀是新一代抗抑郁药物,属于5-羟色胺与去甲肾上腺素再摄取抑制剂。主要用于治疗严重抑郁症、广泛性焦虑症等疾病。目前,国内外市场上的盐酸度洛西汀剂型有肠溶片和肠溶胶囊,肠溶剂型能有效避免药物对胃上皮细胞的刺激和伤害,具有延迟释药的效果。盐酸度洛西汀安全性和耐受性良好,疗效确切且副反应少,因此市场潜力巨大。本课题采用湿法制粒压片包衣工艺制备盐酸度洛西汀肠溶片,以商品制剂与自制制剂的体外释放相似性作为主要评价指标,进行实验探索及优化。优化后的处方为:盐酸度洛西汀含药规格20 mg,原料药平均粒径50μm,填充剂乳糖用量71.32%,微晶纤维素用量15.02%、黏合剂聚维酮90F用量1.50%、崩解剂交联聚维酮用量3.00%、润滑剂硬脂酸镁用量0.75%,隔离层包衣增重5%,肠溶层包衣增重8%。制备工艺:原辅料预混料时间20 min,颗粒干燥时间60 min,烘干温度55℃,总混料时间20 min,片剂硬度7~9 kg,隔离层包衣温度32±2℃,肠溶层包衣温度28±2℃。进行了盐酸度洛西汀肠溶片含量测定高效液相色谱方法学验证,结果表明盐酸度洛西汀浓度在2.24μg/mL~13.44μg/mL范围内线性关系良好;精密度、重复性、准确度、稳定性、耐用性实验RSD均小于2.0%,色谱条件:Agela ODS-2色谱柱(4.6×250 mm,5μm);检测波长230 nm;以pH5.5磷酸盐缓冲溶液-乙腈(58:42)为流动相;柱温40℃;流速1.2 m L/min;进样体积20μL。该法能有效控制产品含量。进行了盐酸度洛西汀肠溶片溶出测定紫外-可见分光光度法方法学验证,结果表明盐酸度洛西汀浓度在2μg/mL~7μg/mL范围内线性关系良好;精密度、稳定性以及准确度的RSD均小于2.0%,可用于溶出度的检测。自制盐酸度洛西汀肠溶片质量检测结果表明片剂外观、片重差异、硬度、脆碎度、水分等指标均符合《中国药典》(2015版)要求。自制片剂的含量、含量均匀度、溶出度、有关物质检测结果均符合盐酸度洛西汀肠溶片(YBH25082O06)。与商品制剂上海中西制药有限公司生产的肠溶片剂“奥思平”体外释放曲线的对比f2相似因子达到75,表明体外释放特性良好。
[Abstract]:Duloxetine Hydrochloride is a new generation of antidepressants, including serotonin and norepinephrine reuptake inhibitors. It is mainly used to treat serious depression, generalized anxiety disorder and other diseases. Doloxetine hydrochloride in the domestic and international markets has enteric-coated tablets and enteric-coated capsules, intestinal solvent type can effectively avoid the stimulation and injury of gastric epithelial cells, and has the effect of delayed release of drugs. Doloxetine hydrochloride has good safety and tolerance. In this paper, doxetine hydrochloride enteric-coated tablets were prepared by wet granulation and pressing, and the in vitro release similarity between commercial preparations and self-made preparations was taken as the main evaluation index. The optimized formulation was as follows: drug specification 20 mg, average particle size 50 渭 m, dosage of lactose 71.32, microcrystalline cellulose 15.02, dosage of polyvinylidene 90F 1.50, disintegrating agent crosslinked polymer 1.50, dosage of microcrystalline cellulose 15.02, dosage of polyveratrol 90F 1.50, disintegrating agent crosslinked polymer 50 渭 m, dosage of lactose 71.32, dosage of microcrystalline cellulose 15.02, dosage of binder polyVitamin 90F 1.50. The dosage of Vetone was 3.00, the amount of lubricant magnesium stearate was 0.75, the coating weight of isolation layer was increased by 5, and the coating weight of enteric coating was increased by 8. The preparation process: raw and auxiliary material premixed material time 20 min, particle drying time 60 min, drying temperature 55 鈩，

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