Online Monitoring of Pharmaceutical Materials Using Multiple NIR Sensors-Part I: Blend Homogeneity

Introduction The present article discusses the implementation of a semi-automated blend homogeneity control system by two near-infrared spectrometers. Methods A statistic was introduced to combine blend trends output by individual instruments based on the root mean squared error from the nominal value calculation. The necessity to monitor homogeneity at more than one location of a V-blender is highlighted and the impact of sensor and model differences on blend trends was evaluated. Using two different formulations, classical least-squares based models were developed to monitor blending. Calibration transfer between the two sensors was demonstrated as a useful approach when more than one sensor is used. Several classical transfer methods were implemented (optical, post-regression correction, and orthogonalization based) to balance the two sensors. Results and Conclusion Results showed that the use of only one calibration model, transferred to all units monitoring the process was highly beneficial to achieving consistent results. Specifically, standardization methods targeting instrument differences were demonstrated to be the most successful. However, results showed that the optimization of a given transfer method was formulation-dependent.