GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore.
J Pharm Sci. 2010 Jan;99(1):346-56. doi: 10.1002/jps.21820.
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.
在底喷流化床包衣过程中,颗粒在分隔室内的再循环是工艺变异性的主要来源。然而,其局部性和复杂性使得操作人员无法察觉。本研究的目的是通过采用基于高速成像和整体相关粒子图像测速(PIV)的可视过程分析仪来获取过程的快照,从而定量颗粒再循环。通过形态图像处理和整体相关 PIV 对底喷流化床包衣器分隔室内的颗粒进行高速成像和研究。通过图像跟踪法对整体相关 PIV 获得的颗粒位移概率密度函数(PDF)进行验证实验,结果表明两者具有一致性。颗粒位移 PDF 进一步分解为颗粒速度大小和颗粒速度方向直方图,这些结果提供了关于颗粒再循环概率的信息,从而定量描述了工艺变异性的主要来源。通过使用所提出的可视过程分析仪,可以更深入地了解颗粒包衣过程,从而更好地控制包衣均匀性。本文提出了可视过程分析仪的概念,并进一步讨论了其在制药过程中的潜在应用。