Measurement of the cumulative particle size distribution of microcrystalline cellulose using near infrared reflectance spectroscopy

The cumulative particle size distribution of microcrystalline cellulose, a widely used pharmaceutical excipient, was determined using near infrared (NIR) reflectance spectroscopy. Forward angle laser light scattering measurements were used to provide reference particle size values corresponding to different quantiles and then used to calibrate the NIR data. Two different chemometric methods, three wavelength multiple linear regression and principal components regression (three components), were compared. For each method, calibration equations were produced at each of eleven quantiles (5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95%). NIR predicted cumulative frequency particle-size distributions were calculated for each of the calibration samples (n = 34) and for an independent test set (n = 23). The NIR procedure was able to predict those obtained via forward angle laser light scattering.