Development of high speed video imaging as a process analytical technology (PAT) tool

Abstract

This PhD project explored the development of high speed video imaging as a process analytical technology (PAT) tool for better understanding and control of two major multiparticulate manufacturing processes, i.e. extrusion-spheronization and bottom spray fluid bed coating. Particle image velocimetry and image processing were employed for analysis of high speed images to elucidate in-process material flow pattern. From the investigations on the spheronization process, a refined model of particle growth kinetics was proposed. The particle flow patterns in the near frictional base plate region and bed surface were investigated and correlated with particle growth kinetics. It was found that spheronization process monitoring and endpoint determination could be achieved by monitoring particle motion either in the near plate region or in the spheronization bed surface. In the investigations on bottom spray fluid bed coating, the particle motion in the upbed region, fountain region and annular bed region were quantified. With the developed PAT tool, cluster formation and drag reduction were found to be the mechanisms of particle recirculation within the partition column. Real-time measurement of particle mass flow rate was achieved. The influences of annular bed flow patterns on coat uniformity were also clearly demonstrated for the first time.