Optimization of a high shear wet granulation process using focused beam reflectance measurement and particle vision microscope technologies

Application of process analytical technology in the pharmaceutical industry has led to a great number of studies into inline instrumentation. Near‐infrared moisture monitoring in fluid bed drying and content uniformity assurance in blending are gaining acceptance for monitoring and quality control of these processes. Although these techniques are a great improvement over traditional methods, each is performed at points in processing wherein processing is well understood and interfacing equipment is relatively easy. More complex unit operations have largely been unexplored due to complexities interfacing inline analytical equipment to unit operations or a lack of methodologies that can be applied to measure attributes of interest. This paper reports results from a study utilizing a focused beam reflectance measurement system equipped with window scraper technology for the inline measurement and control of a high shear wet granulation (HSWG) process. In addition to this, offline results obtained with a particle vision microscope system are compared to verify the results obtained inline. It is shown that using these technologies in monitoring the HSWG process greatly increases process understanding of physical changes occurring during processing through real‐time observation of particle size, leading to real‐time control of the process. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3431-3440, 2011