过程分析技术
造粒
关键质量属性
颗粒(地质)
设计质量
工艺工程
材料科学
生物系统
实验设计
计算机科学
在制品
数学
统计
粒径
工程类
复合材料
化学工程
生物
运营管理
作者
Wei Meng,Andrés D. Román-Ospino,Savitha S. Panikar,Chris O'Callaghan,Sean J. Gilliam,Rohit Ramachandran,Fernando J. Muzzio
标识
DOI:10.1016/j.apt.2019.01.017
摘要
Process analytical technologies (PAT) are identified as an essential element in the Quality by Design framework, providing the cornerstone to implement continuous pharmaceutical manufacturing. This study is concerned with employing three in-line PATs: Eyecon™ 3D imaging system, Near-infrared spectroscopy (NIRS) and Raman spectroscopy (RS), in a continuous twin-screw granulation process to enable real-time monitoring and prediction of critical quality attributes of granules. The Thermo Scientific™ Pharma 11 twin-screw granulator was used to manufacture granules from a low-dose formulation with caffeine anhydrous as the model drug. A 30-run full factorial design including three critical process parameters (liquid to solid ratio, barrel temperature and throughput) was conducted to evaluate the performance of each analytical tool. Eyecon™ successfully captured the granule size and shape variation from different experimental conditions and demonstrated sufficient sensitivity to the fluctuation of size parameter D10 in the presence of process perturbations. The partial least square regression (PLSR) models developed using NIRS showed small relative standard error of prediction values (less than 5%) for most granule physical properties. In contrast, the RS-based PLSR models revealed higher prediction errors towards granule drug concentration, potentially due to the inhomogeneous premixing of raw materials during calibration model development.
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