A Case Study on the Use of End-to-End Real-time Monitoring to Ensure Quality of Oral Solid Dosage Forms in...

The integration of Process Analytical Technology (PAT) into pharmaceutical process development has become a critical focus since the issuance of FDA PAT guidance in 2004. While PAT applications for blend uniformity (BU) and content uniformity (CU) are well-established, their utilization in early-phase development in an end-to-end fashion is seldomly reported. This study presents a novel case of deploying end-to-end PAT capabilities, combined with material-sparing chemometric approaches, to mitigate the impact of coarse API particle size distribution on BU and CU. Near-infrared spectroscopy (NIRS) data were collected across three interfaces-bin-blender, tablet press feedframe, and tablets-to generate high-density real-time process data. Chemometric modeling via Classical Least Squares (CLS) was employed to translate spectra into actionable concentration data without the need for additional API calibration samples. Furthermore, this study provides a comparative analysis of CLS based upon measured versus estimated pure component spectra, highlighting the advantages and limitations of each approach. The findings underscore the potential of material-sparing PAT methods to enhance process understanding and robustness in early-phase development. The results also set the stage for broader adoption of PAT and phase-appropriate method development, fostering innovation in pharmaceutical research and development.