基于聚氧乙烯的米拉贝隆缓释片的处方研究  

Application of Polyethylene Oxide in Mirabegron Extended-Release Tablets

作　　者：王如意 杜志永 熊锋 蔡莹俊 黄刘昂 高昊 夏婷婷 WANG Ruyi;DU Zhiyong;XIONG Feng;CAI Yingjun;HUANG Liuang;GAO Hao;XIA Tingting(Pharma Solution,Danisco Biotech(Shanghai)Limited Company,Shanghai 200335,China)

机构地区：[1]丹尼斯克生物科技(上海)有限公司药品解决方案事业部,上海200335

出　　处：《中国药学杂志》2024年第10期921-928,共8页Chinese Pharmaceutical Journal

摘　　要：目的考察IFF公司的聚氧乙烯(POLYOXTM,商品名:保益乐)、促渗透剂和抗氧化剂丁基羟基甲苯(BHT)对米拉贝隆缓释片释放度的影响。以期为开发聚氧乙烯缓释片提供一些配方经验。方法采用单因素实验考察配方中聚氧乙烯的相对分子质量、粒径和用量,不同种类促渗透剂[聚乙二醇(PEG)8000、PEG 4000和乳糖]和BHT的用量对米拉贝隆缓释片释放度的影响。结果聚氧乙烯WSR N60K在用量28%时制得的米拉贝隆缓释片与市售贝坦利?米拉贝隆缓释片(RLD)具有统计学相似的释放度。高相对分子质量和高用量的聚氧乙烯得到较慢的药物释放,而低相对分子质量和低用量的聚氧乙烯导致更快的药物释放。聚氧乙烯WSR N60K的粒径大小对米拉贝隆缓释片的释放度无显著影响。不论是使用聚乙二醇(PEG 8000或4000)还是乳糖作为促渗透剂,制备的缓释片均具有与RLD片相似的释药效果。聚氧乙烯WSR 301和N12K以35∶65的比例得到的混合物与聚氧乙烯WSR N60K具有相同的黏度,制备的缓释片也具有统计学相似的药物释放度。结论聚氧乙烯是良好的亲水凝胶骨架材料,其制得的米拉贝隆缓释片处方稳健,释药稳定。OBJECTIVE To investigate the impact of polyethylene oxide(PEO,POLYOXTM),penetration additives,and butylated hydroxytoluene(BHT)on tablet properties and drug release of mirabegron extended release(ER)tablets and provide some ideas of formulating polyethylene oxide based ER tablets for the formulators.METHODS Single-factor-experiment was applied to investigate the impact of formulation components on drug release of mirabegron ER tablets.Different molecular weight(MW),series of particle size and use level of polyethylene oxide,three types of penetration additives(PEG 8000,PEG 4000 and lactose)and several use levels of butylated hydroxytoluene(BHT)were investigated.RESULTS Mirabegron ER tablets formulated with polyethylene oxide WSR N60K at 28%use level got statistically equivalent drug release with marketed mirabegron ER tablets.Higher MW and higher use level of polyethylene oxide led to slower drug release,while lower MW and lower use level led to faster drug release.Particle size of polyethylene oxide WSR N60K did not significantly affect mirabegron drug release.The tablets using either polyethylene glycol(PEG 8000 or 4000)or lactose as penetration additives could achieve equivalent drug release as marketed mirabegron ER tablets.The blend of polyethylene oxide WSR 301 and N12K at ratio of 35∶65 has the same viscosity with polyethylene oxide WSR N60K and led to statistically similar drug release.CONCLUSION Formulation of polyethylene oxide based mirabegron ER tablets are robust.

关 键 词：聚氧乙烯 缓释片 米拉贝隆 丁基羟基甲苯 

分 类 号：R944[医药卫生—药剂学]