IN-LINE NEAR INFRARED SPECTROSCOPY MONITORING OF PHARMACEUTICAL POWDER MOISTURE IN A FLUIDISED BED DRYER: AN EFFICIENT METHODOLOGY FOR CHEMOMETRIC MODEL DEVELOPMENT Anne-Marie Demers, 1 Ryan Gosselin, 1 Jean-S´ ebastien Simard 2 and Nicolas Abatzoglou 1 * 1. Universit´ e de Sherbrooke, Department of Chemical and Biotechnological Engineering, Pfizer Industrial Research Chair on PAT in Pharmaceutical Engineering, Sherbrooke, Quebec, Canada 2. Process Analytical Science Group, Global Manufacturing Services, Pfizer, Montreal, Quebec, Canada This work proposes a novel chemometric methodology for in-line near infrared spectroscopy (NIRS) monitoring of pharmaceutical powder moisture in a fluidised-bed dryer. The collected spectra are analysed by multivariate chemometrics involving the preparation of numerous laboratory samples. A different methodology, using only plant samples, was tested in real-time. A specially designed probe tip, allowing for robust in-situ spectral acquisition, was designed. The results prove that NIRS can be as efficient as traditional quality analyses, e.g. loss-on-drying, in measuring powder moisture content in a fluidised bed dryer with a calibration model based only on plant samples. Keywords: near infrared (NIR), process analytical technologies, fluidised-bed dryer, chemometrics, in-line INTRODUCTION H igh product yield and consistent product quality have always been of paramount importance to the pharma- ceutical industry. However, even if current practices ensure highly finished product quality, there are opportunities for improvements in monitoring and testing in-process and final product quality attributes. Indeed, traditional quality analyses are usually destructive, expensive and time-consuming. This has led to an initiative of the Food and Drug Administration for the use of in-line spectroscopic techniques, such as near infrared spec- troscopy (NIRS), to accelerate the quality control process (U.S. Department of Health and Human Services, 2004). In the pharmaceutical industry, the drying of powders in flu- idised bed dryers is usually preferred to traditional static ovens because it is a faster process and ensures more homogeneous moisture content of intermediate products. At the end of this unit operation, 2 quality analyses, namely, Karl–Fischer titration and loss-on-drying (LOD), traditionally are used to determine the water content of representative dried powder samples. How- ever, these tests are often time-consuming, costly, intrusive and destructive. The intensive development of NIRS over the past 10 years has turned it into a fast and robust non-destructive technology. NIRS can now be considered as an in-line process analytical technology that can quantify powder moisture content in a fluidised bed dryer in real-time with precision rivaling that of Karl–Fischer titration or LOD (Frake et al., 1997; Green et al., 2005; Nieuwmeyer et al., 2007; GEA Pharma Systems, 2009; Corredor et al., 2010). To assess moisture content in a fluidised bed dryer, most exper- iments with an invasive NIRS probe are performed in static conditions since it is difficult to acquire spectra in dynamic envi- ronments (Green et al., 2005). The probe must also be located at an appropriate height and angle relative to the fluidised bed dryer bowl despite the fact that optimal values of these parame- ters are not always easy to establish (GEA Pharma Systems, 2009). ∗ Author to whom correspondence may be addressed. E-mail address: nicolas.abatzoglou@usherbrooke.ca Can. J. Chem. Eng. 90:299–303, 2012 © 2011 Canadian Society for Chemical Engineering DOI 10.1002/cjce.20691 Published online 14 December 2011 in Wiley Online Library (wileyonlinelibrary.com). | VOLUME 90, APRIL 2012 | | THE CANADIAN JOURNAL OF CHEMICAL ENGINEERING | 299 |