Near infrared analysis of pharmaceutical powders with empirical target distribution optimization (ETDO)

Near infrared (NIR) spectroscopy is a well-established method for analysis of pharmaceutical products, and especially useful for process monitoring and control of continuous production due to high sample throughput. In this work, a previously established method called empirical target distribution optimization (ETDO) wherein reference sample values using information from model prediction of the calibration data was used as a tool to improve the performance of NIR partial least squares (PLS) models. Model performance was assessed using root mean square error (R²), bias and accuracy in prediction of test samples. A target value selection threshold was tested to assess the ETDO procedure for NIR analysis of powder samples. The amount of specific variation captured by the model was examined and compared for models calibrated with and without ETDO. The results reported in this work suggests that PLS models optimized with ETDO of reference values can provide more specific PLS models for NIR analysis for complex powder mixtures. In addition, the model optimization method could also be applied as a tool to verify the necessary amount of PLS components to produce robust models. The ETDO method presented in this work is an approach that could be applied in the development of continuous blending or tableting processes where robust in-line quantitative analysis of powder samples is needed.