The present study introduces a new in situ near-infrared chemical imaging technique (imMix (TM)) designed to characterize micro-mixing in pharmaceutical powder blends. The technique uses in-line, non-contact monitoring of the blending process, eliminating the bias introduced by commonly used powder sampling techniques. A Science-Based Calibration (SBC) chemometric method, which uses pure component spectral data to create a calibration model, was used to create concentration maps of the blends studied here. The advantage of SBC over the alternative Partial Least Squares (PLS) or Principal Component Analysis (PCA) calibration methods is that it does not require a large number of samples to create a calibration. The imMix system proved to be useful in monitoring the spatial distribution and aggregate sizes of acetaminophen, used as the model drug, and of excipients in the blends. Using a 1-1 bin blender, measurements were able to detect changes in the constituents and other experimental parameters as a function of blending time Such measurements can be used to determine the mixing time and shear requirements of blends during product and process development. (C) 2013 Elsevier Ltd. All rights reserved