摘要
目的为普瑞巴林口服溶液仿制制剂的研发提供参考。方法以普瑞巴林口服溶液参比制剂为研究对象,采用逆向工程对制剂进行处方分析和小试工艺研究。采用高效液相色谱(HPLC)法测定抑菌剂羟苯甲酯、羟苯丙酯的含量,并进行抑菌效力检查;采用紫外分光光度法结合pH检测法测定缓冲液磷酸二氢钠一水合物与磷酸氢二钠十二水合物的含量;采用HPLC法测定甜味剂三氯蔗糖的含量;根据口味和性状调整芳香剂草莓香精的加入量;结合单因素试验筛选原辅料的溶解温度及配制顺序,确定制剂的小试工艺。结果生产规格为20 mg/mL(200 mL)的普瑞巴林口服溶液时,以85℃溶解羟苯甲酯0.25 g与羟苯丙酯0.033 g,降温至30℃时依次加入磷酸二氢钠一水合物0.748 g、磷酸氢二钠十二水合物0.210 g、普瑞巴林4 g、三氯蔗糖0.65 g、草莓香精0.1 g,搅拌至完全溶解,加80 mL纯化水,搅拌20 min至均匀,即得。结论所制备的普瑞巴林口服溶液质量稳定,可为仿制制剂的研发提供参考。
Objective To provide a reference for the development of generic Pregabalin Oral Solution.Methods The reference preparation of Pregabalin Oral Solution was taken as the research object,and reverse engineering was used for prescription analysis and small-scale process research of preparations.High-performance liquid chromatography(HPLC) method was used for the content determination of antibacterial agents hydroxybenzoate and hydroxypropyl ester,and the antibacterial efficacy test was conducted.Ultraviolet(UV) spectrophotometry combined with pH detection method was used for the content determination of buffering agents sodium dihydrogen phosphate monohydrate and sodium dihydrogen phosphate dodecahydrate.HPLC method was used for the content determination of sweetener sucralose.The amount of strawberry essence was adjusted according to taste and character.The dissolution temperature and preparation sequence of raw materials and excipients were screened by the single factor test,and the small-scale process of Pregabalin Oral Solution was determined.Results The Pregabalin Oral Solution with the specification of 20 mg/mL(200 mL) was dissolved at 85 ℃ with 0.25 g of hydroxybenzoate and 0.033 g of hydroxypropyl ester.After cooling down to 30 ℃,0.748 g of sodium dihydrogen phosphate monohydrate,0.210 g of sodium hydrogen phosphate dodecahydrate,4 g of pregabalin,0.65 g of sucralose and 0.1 g of strawberry essence were added successively,and stirred until completely dissolved,80 mL of purified water were added and stirred for 20 min until uniform.Conclusion The quality of Pregabalin Oral Solution prepared by this method is stable,which can provide a reference for the development of generic drugs.
作者
杨凯歌
张梦婷
吴雪英
王昕
黄志军
YANG Kaige;ZHANG Mengting;WU Xueying;WANG Xin;HUANG Zhijun(Chemical Engineering and Life Science,Wuhan University of Technology,Wuhan,Hubei,China 430070;Jianmin Pharmaceutical Group Co.,Ltd.,Wuhan,Hubei,China 430050)
出处
《中国药业》
CAS
2024年第15期42-48,共7页
China Pharmaceuticals
关键词
普瑞巴林口服溶液
逆向工程
处方研究
小试工艺
Pregabalin Oral Solution
reverse engineering
prescription research
small-scale process
