Meng Wei, Kotamarthy Lalith, Panikar Savitha, Sen Maitraye, Pradhan Shankali, Marc Michaelis, Litster James D, Muzzio Fernando J, Ramachandran Rohit
Department of Pharmaceutics, Rutgers University, Piscataway, NJ 08854, USA.
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
Int J Pharm. 2016 Nov 20;513(1-2):357-375. doi: 10.1016/j.ijpharm.2016.09.041. Epub 2016 Sep 12.
This study is concerned with identifying the design space of two different continuous granulators and their respective granulation mechanisms. Performance of a continuous high shear granulator and a twin screw granulator with paracetamol formulations were examined by face-centered cubic design, which focused on investigating key performance metrics, namely, granule size, porosity, flowability and particle morphology of granules as a function of essential input process parameters (liquid content, throughput and rotation speed). Liquid and residence time distribution tests were also performed to gain insights into the liquid-powder mixing and flow behavior. The results indicated that continuous high shear granulation was more sensitive to process variation and produced spherical granules with monomodal size distribution and distinct internal structure and strength variation. Twin screw granulation with such a particular screw configuration showed narrower design space and granules were featured with multimodal size distribution, irregular shape, less detectible porosity difference and tighter range of strength. Granulation mechanisms explored on the basis of nucleation and growth regime maps revealed that for most cases liquid binder was uniformly distributed with fast droplet penetration into the powder bed and that granule consolidation and coalescence mainly took place in the nucleation, steady growth and rapid growth regimes.
本研究旨在确定两种不同连续制粒机的设计空间及其各自的制粒机制。采用面心立方设计考察了连续高剪切制粒机和双螺杆制粒机对扑热息痛制剂的性能，重点研究关键性能指标，即颗粒尺寸、孔隙率、流动性以及颗粒形态与基本输入工艺参数（液体含量、产量和转速）之间的函数关系。还进行了液体和停留时间分布测试，以深入了解液粉混合和流动行为。结果表明，连续高剪切制粒对工艺变化更为敏感，制得的颗粒呈球形，具有单峰尺寸分布以及明显的内部结构和强度变化。具有这种特定螺杆配置的双螺杆制粒显示出较窄的设计空间，颗粒具有多峰尺寸分布、不规则形状、孔隙率差异较难检测以及强度范围较窄的特点。基于成核和生长区域图探索的制粒机制表明，在大多数情况下，液体粘合剂均匀分布，液滴快速渗透到粉末床中，颗粒固结和聚结主要发生在成核、稳定生长和快速生长阶段。
