Particle Scale Insights into a KG-Pharma RoTab Tablet Press Feed-Frame System Using the Discrete Element Method (DEM) Modeling

Abstract

In the pharmaceutical industry, tablets are a common dosage form. As part of the manufacturing process, powder in a tablet press passes through a feeding system called the feed-frame before reaching the die cavity. Under different manufacturing conditions (e.g., paddle speed, turret speed), issues such as segregation of powder blend components, over lubrication, and drug particle attrition often occur in the tablet press feed-frame, which affect the final drug product quality. Therefore, developing a particle-scale understanding of powder behavior in a feed-frame is essential. This paper used the discrete element method (DEM) to study powder flow in the feed-frame of a kg-pharma RoTab tablet press. Simulation results show that an increase in paddle speed has less effect on tablet mass than turret speed and that an increase in turret speed reduces tablet mass and increases variability in the tablet mass. The effect of paddle speed and turret speed on the API content in the tablet is small, but large paddle speeds exacerbate the segregation of powder blend components in the feed frame, increase particle traveled distance, particle shear work, and torque on the paddle wheel, thereby increasing particle over lubrication and attrition. However, the increase in paddle speed reduces the mean residence time of drug particles and prevents over lubrication at low turret speeds. Increasing the turret speed reduces tablet mass, particle shear work, paddle torque, and mean residence time. Although increasing turret speed can effectively prevent particle attrition and over lubrication, short residence times are not conducive to mixing excipients and API components, leading to higher tablet mass variability. This study not only gives us a particle-level insight into the process but can also be used to inform and optimize the design of experimental studies.