Abstract：
The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett-Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.
摘要：
这项研究的目的是使用质量设计（QbD）方法优化片剂压缩过程和确定影响关键质量属性（CQAs）的薄膜包衣关键过程参数（CPP）。采用实验设计(DOE)和回归方法研究硬度，崩解时间,和未包衣片剂的厚度取决于压片和压片压缩力(CPPs)。Plackett-Burman实验设计用于确定选定的关键涂层工艺参数：干燥和预热时间，雾化空气压力，喷雾速率,风量,进气温度,和可能影响包衣片剂的硬度和崩解时间的转鼓压力。作为研究的结果,建立了设计空间，以促进对CPPs和中间产品（未包衣片剂）的CQA之间的现有关系的深入了解。筛选表明，喷雾速率和入口空气温度是影响包衣片剂硬度的两个最重要因素。同时,所测试的包衣因素对崩解时间没有影响。通过进行中试大小批次的膜包衣来证实观察。
