摘要
基于质量源于设计的理念,以已上市的普瑞巴林缓释片为参比制剂,确定自制胃滞留缓释片的目标产品质量概况(QTPP)和关键质量属性(CQAs)。采用单因素试验结合星点设计-响应面法,以起漂时间、持续漂浮时间,以及不同时间点(1、4、24 h)的累积释放率为因变量,优化了处方中聚乙酸乙烯酯和聚维酮混合物(Kollidon SR)、聚氧乙烯、卡波姆及交联聚维酮的用量。通过绘制三维响应面图,得到了优化处方比例:Kollidon SR 19.25%、聚氧乙烯15.50%、卡波姆3.25%、交联聚维酮31.50%。经验证,优选的普瑞巴林胃滞留缓释片1、4、24 h累积释放率实测值分别为17.12%、43.73%、97.19%,且与参比制剂的体外释放行为一致;起漂时间30 s,持续漂浮时间大于10 h,也符合设计要求。
Based on the concept of Quality by Design, the quality target product profile(QTPP) and critical quality attributes(CQAs) of the self-made generic-retentive sustained-release tablets were defined with the marketed pregabalin sustained-release tablets as the reference listed drug. The amounts of a blend of polyvinyl acetate and povidone(Kollidon SR), polyoxyethylene, carbomer and crospovidone were optimized by single factor test combined with central composite design-response surface methodology with floating lag time, long floating duration and cumulative release rates at different sampling points(1, 4 and 24 h) as the dependent variables. By drawing the three-dimensional response surface plots, the optimized formulation parameters were obtained as follows: 19.25% of Kollidon SR, 15.50%of polyoxyethylene, 3.25% of carbomer, and 31.50% of crospovidone. The cumulative release rates at 1, 4 and 24 h of the optimized formulation were respectively 17.12%, 43.73% and 97.19% in the validation test, and the release behaviors between the self-made tablets and the resfecence listed drug were similar. The floating lag time was 30 s and long floating duration was over 10 h, indicating the floating characteristics of the self-made tablets met the design requirements.
作者
姚钰
林华庆
张佳琪
刘寒冰
彭程
YAO Yu;LIN Huaqing;ZHANG Jiaqi;LIU Hanbing;PENG Cheng(Guangdong Provincial Key Lab.of Advanced Drug Delivery,Guangdong Pharmaceutical University,Guangzhou 510006)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2023年第1期93-100,共8页
Chinese Journal of Pharmaceuticals
基金
广东省科学技术厅-广东省中医药科学院联合科研项目资助(2016A020226038)
广东省省级科技计划项目资助(2013B090800007)。
关键词
质量源于设计
普瑞巴林
胃滞留缓释片
处方优化
Quality by Design
pregabalin
gastric-retentive sustained-release tablet
formulation optimization
