Development of a visiometric process analyzer for real-time monitoring of bottom spray fluid-bed coating

Particle recirculation within the partition column is a major source of process variability in the bottom spray fluid-bed coating process. However, its locality and complex nature make it hidden from the operator. The aim of this study was to take snapshots of the process by employing a visiometric process analyzer based on high-speed imaging and ensemble correlation particle image velocimetry (PIV) to quantify particle recirculation. High-speed images of particles within the partition column of a bottom spray fluid-bed coater were captured and studied by morphological image processing and ensemble correlation PIV. Particle displacement probability density function (PDF) obtained from ensemble correlation PIV was consistent with validation experiments using an image tracking method. Particle displacement PDF was further resolved into particle velocity magnitude and particle velocity orientation histograms, which gave information about particle recirculation probability, thus quantifying the main source of process variability. Deeper insights into particle coating process were obtained and better control of coat uniformity can thus be achieved with use of the proposed visiometric process analyzer. The concept of visiometric process analyzers was proposed and their potential applications in pharmaceutical processes were further discussed. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:346-356, 2010