ABSTRACT

The present investigation was computational predictability of Polyethylene Glycol (PEG) encapsulated modified release multiple unit pellets system (MUPS) tablet of Metoprolol succinate by quality by design (QbD). Quality target product profile (QTPP) and critical quality attributes (CQAs) of MUPS tablets were defined. Risk assessment was done using Ishikawa diagram and failure mode effect analysis (FMEA) as per ICH Q8 guidelines. Formulation was screened and optimized using Plackett–Burman and Box– Behnken design. Pellets were prepared by wruster coating system-using polymers such as hydroxypropyl methylcellulose (HPMC), Ethyl cellulose (EC) with other excipients. Formulation variables X1: HPMC and X2: EC have affected the drug release (Y1). PEG capsulation ensures the intactness of film after compression. ANOVA results confirm the selected model was statistically significant. This investigation demonstrated the PEG encapsulated HPMC and EC polymer coated with optimised curing time will achieve a single dose of metoprolol succinate applying QbD.

摘要

目前的研究是聚乙二醇 (PEG) 包封的改良释放多单位微丸系统 (MUPS) 片剂的质量设计 (QbD) 的计算可预测性。定义了 MUPS 片剂的质量目标产品概况 (QTPP) 和关键质量属性 (CQAs)。根据 ICH Q8 指南，使用 Ishikawa 图和失效模式影响分析 (FMEA) 进行风险评估。使用 Plackett-Burman 和 Box-Behnken 设计筛选和优化配方。通过使用诸如羟丙基甲基纤维素 (HPMC)、乙基纤维素 (EC) 等聚合物和其他赋形剂的 wruster 包衣系统制备丸剂。配方变量 X1：HPMC 和 X2：EC 影响了药物释放（Y1）。PEG封装确保压缩后薄膜的完整性。ANOVA 结果证实所选模型具有统计学意义。该研究表明，涂有优化固化时间的 PEG 封装的 HPMC 和 EC 聚合物将实现单剂量的琥珀酸美托洛尔应用 QbD。