Characteristics of residence time distribution (RTD) in a continuous high shear mixer granulation were investigated to promote the development of a continuous manufacturing process in the pharmaceutical industry. A continuous granulator with an impeller and a scraper was utilized. The tracer behavior in the continuous wet granulation was verified in impulse-response experiments with acetaminophen. The RTD of acetaminophen changed depending on the scraper speed (15–50 rpm), and the mean residence time could be adjusted by the scraper speed in the wet granulation. The impact of changes in the liquid-to-solid ratio (0.10–0.20) and the addition of binder were also examined, and the variance of RTD was influenced by both. The degree of axial mixing was quantitatively evaluated with a dimensionless index, the Peclet number (Pe). Higher scraper speed was found to suppress fluctuations of the axial mixing that occurred with changes in the liquid feed. Moreover, the transition of granule size distribution with the change in liquid feed reached a steady state more quickly under the higher scraper speed. These results show that scraper rotation can help to adjust the RTD and the axial mixing, leading to a more robust continuous granulation.

研究了连续高剪切混合器制粒中停留时间分布 (RTD) 的特征，以促进制药行业连续制造工艺的发展。使用带有叶轮和刮刀的连续造粒机。在对乙酰氨基酚的脉冲响应实验中验证了连续湿法制粒中的示踪剂行为。对乙酰氨基酚的 RTD 随刮刀速度（15-50 rpm）而变化，平均停留时间可以通过湿法制粒中的刮刀速度进行调整。还检查了液固比 (0.10–0.20) 变化和粘合剂添加的影响，RTD 的方差受两者影响。轴向混合的程度用无量纲指数、佩克莱数 (Pe) 进行定量评估。发现较高的刮刀速度可以抑制随着液体进料变化而发生的轴向混合的波动。此外，在较高的刮刀速度下，颗粒尺寸分布随液体进料变化的转变更快地达到稳定状态。这些结果表明刮刀旋转有助于调整 RTD 和轴向混合，从而实现更稳定的连续造粒。