本文關鍵詞： 鹽酸度洛西汀 腸溶片 制備研究 質量分析 抗抑郁　出處：《河北科技大學》2017年碩士論文　論文類型：學位論文

【摘要】：鹽酸度洛西汀是新一代抗抑郁藥物,屬于5-羥色胺與去甲腎上腺素再攝取抑制劑。主要用于治療嚴重抑郁癥、廣泛性焦慮癥等疾病。目前,國內外市場上的鹽酸度洛西汀劑型有腸溶片和腸溶膠囊,腸溶劑型能有效避免藥物對胃上皮細胞的刺激和傷害,具有延遲釋藥的效果。鹽酸度洛西汀安全性和耐受性良好,療效確切且副反應少,因此市場潛力巨大。本課題采用濕法制粒壓片包衣工藝制備鹽酸度洛西汀腸溶片,以商品制劑與自制制劑的體外釋放相似性作為主要評價指標,進行實驗探索及優(yōu)化。優(yōu)化后的處方為:鹽酸度洛西汀含藥規(guī)格20 mg,原料藥平均粒徑50μm,填充劑乳糖用量71.32%,微晶纖維素用量15.02%、黏合劑聚維酮90F用量1.50%、崩解劑交聯(lián)聚維酮用量3.00%、潤滑劑硬脂酸鎂用量0.75%,隔離層包衣增重5%,腸溶層包衣增重8%。制備工藝:原輔料預混料時間20 min,顆粒干燥時間60 min,烘干溫度55℃,總混料時間20 min,片劑硬度7~9 kg,隔離層包衣溫度32±2℃,腸溶層包衣溫度28±2℃。進行了鹽酸度洛西汀腸溶片含量測定高效液相色譜方法學驗證,結果表明鹽酸度洛西汀濃度在2.24μg/mL~13.44μg/mL范圍內線性關系良好;精密度、重復性、準確度、穩(wěn)定性、耐用性實驗RSD均小于2.0%,色譜條件:Agela ODS-2色譜柱(4.6×250 mm,5μm);檢測波長230 nm;以pH5.5磷酸鹽緩沖溶液-乙腈(58:42)為流動相;柱溫40℃;流速1.2 m L/min;進樣體積20μL。該法能有效控制產品含量。進行了鹽酸度洛西汀腸溶片溶出測定紫外-可見分光光度法方法學驗證,結果表明鹽酸度洛西汀濃度在2μg/mL~7μg/mL范圍內線性關系良好;精密度、穩(wěn)定性以及準確度的RSD均小于2.0%,可用于溶出度的檢測。自制鹽酸度洛西汀腸溶片質量檢測結果表明片劑外觀、片重差異、硬度、脆碎度、水分等指標均符合《中國藥典》(2015版)要求。自制片劑的含量、含量均勻度、溶出度、有關物質檢測結果均符合鹽酸度洛西汀腸溶片(YBH25082O06)。與商品制劑上海中西制藥有限公司生產的腸溶片劑“奧思平”體外釋放曲線的對比f2相似因子達到75,表明體外釋放特性良好。
[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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