Assessment of chemometric methods for the non-invasive monitoring of solid blending processes using wireless near infrared spectroscopy

The US Food and Drug Administration's process analytical technology (PAT) initiative has encouraged the pharmaceutical industry to strengthen research with a view to developing new analytical technologies for improving blending processes. Near infrared (NIR) spectroscopy, which is sensitive to both physical and chemical attributes of substances, has proved a powerful non-invasive analytical technique for this purpose. In this paper, we propose a criterion to assess blending uniformity and accurately detect the end-point of a blending process. The criterion was established by using partial least squares (PLS) regression and calibration-free methods including moving block standard deviation of spectra, principal component scores distance analysis and the mixing index (M). The mixing index was found to provide accurate, robust results with a view to assessing blending uniformity, as was PLS for detecting blending endpoints. This novel criterion allowed us to assess the homogeneity of a mixture, without the need of a reference method, a golden batch or a calibration set. In fact, the M index was found to be an easy method and it is a highly suitable tool for PAT as it allows the accurate, precise real-time monitoring of blending processes with minimal intervention of the analyst. © IM Publications LLP 2013. All rights reserved.