盐酸伊伐布雷定单层渗透泵控释片的制备与体外释药行为  

Preparation and in vitro release of ivabradine hydrochloride elementary osmotic pump tablets

作　　者：施沁青 王菁华 程曼曼 尹莉芳 秦超 SHI Qinqing;WANG Jinghua;CHENG Manman;YIN Lifang;QIN Chao(Department of Pharmaceutics,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药学院药剂系,南京210009

出　　处：《中国药科大学学报》2021年第3期311-317,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81871477)。

摘　　要：制备日服1次的盐酸伊伐布雷定(IVB)单层渗透泵控释片。建立了释放度测定方法,单因素考察助悬剂、促渗剂和老化条件等对释药曲线的影响。以片芯中聚氧乙烯(PEO)的用量、控释衣膜中聚乙二醇(PEG)的比例和包衣增重进行3因素3水平的正交设计。最终处方为IVB 16.25 mg,PEO N8060 mg,羟丙甲基纤维E510 mg,乳糖111.75 mg,硬脂酸镁2 mg;包衣液中PEG 15%,醋酸纤维素85%,包衣增重7.5%。体外释药行为表明,药物释放不受环境pH影响,无剂量倾泻风险,释药动力为膜内外渗透压差。IVB渗透泵片能够降低给药次数,提高患者的顺应性,具有临床应用价值。In this study,ivabradine hydrochloride(IVB)was prepared as elementary osmotic pump tabletswhose administration frequency was reduced to once daily.The dissolution method was developed,and effects ondrug release profiles were evaluated by single factor analysis involving suspending agents,osmotic active agentsand aging process.Orthogonal test was carried out at 3 levels on 3 factors including the amount ofpolyoxyethylene(PEO)in the core,polyethylene glycol(PEG)percentage and weight increase of controlledrelease film coatings.The final formulation consisted of IVB(16.25 mg),PEO N80(60 mg),hypromellose E5(10 mg),lactose(111.75 mg),magnesium stearate(2 mg);and the film coatings consisted of PEG(15%),cellulose acetate(85%),with a weight increase of 7.5%.In vitro drug release behaviors were investigated.Prepared tablets exhibited similar release profiles in different p H dissolution media,with no risk of dose dumpingin 40%ethanol solutions.The osmotic pressure differences inside and outside the membrane drove drug release.IVB osmotic pump tablets could reduce the frequency of administration and improve patients’compliance,thuswith better application values.

关 键 词：伊伐布雷定 渗透泵 制备 体外释放 正交设计 剂量倾泻 

分 类 号：R944[医药卫生—药剂学]