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.

• Powrex Corp

• Oral solid dose
• Process characterization

1. continuous manufacturing
2. oral solid dose
3. Peclet number
4. Pharmaceutical granulation
5. Process characterization
6. Research Article
7. residence time distribution