Near Infrared Method Development for a Continuous Manufacturing Blending Process

Abstract

This study describes the validation of a near infrared spectroscopic method for monitoring a continuous manufacturing system. The achievement of this goal requires determining the near infrared (NIR) method’s accuracy, precision, obtaining an estimate of the sample volume analyzed, and the frequency with which measurements should be obtained. Five calibration blends were prepared spanning a concentration range from 7 to 13 % w/w ibuprofen to prepare a partial least squares (PLS) calibration model for a five component formulation. NIR spectra were obtained after powders passed through feeders and a custom-made tumble mixer. The calibration model’s precision and accuracy were determined with the prediction of three validation blends. NIR concentration predictions obtained from spectra collected during the validation runs showed relative standard errors of predictions of 2.8 % at target concentration with standard deviations NMT 0.2 % w/w. At certain time points, blend samples coming out of the blender were collected for UV analysis. Results from the NIR and UV analysis were comparable with the largest difference being 0.36 % w/w between the methods. A continuous blending process was monitored for 3 min after steady-state conditions were achieved. All individual predictions were within 3 standard deviations of the average reference value. The standard deviation for the NIR concentration predictions was 0.49 % w/w. The use of the standard normal variate (SNV) transform significantly reduced the effect of differences in powder flow on the NIR predictions. The use of variograms provided valuable insight into the frequency of measurements needed for the continuous manufacturing system. Additional research is needed to investigate the differences observed in the NIR and UV results for the continuous manufacturing run.