Direct comparison of near-infrared spectroscopy with near-infrared spatially resolved spectroscopy for monitoring active pharmaceutical ingredient concentration in a feed frame simulator.

As pharmaceutical manufacturing shifts towards continuous processing and increasingly potent, low-dose Active Pharmaceutical Ingredient (API) products, there is a growing need for more accurate and reliable Process Analytical Technology (PAT). This study presents a direct, side-by-side comparison of Near-Infrared (NIR) spectroscopy and Near-Infrared Spatially Resolved Spectroscopy (NIR-SRS) for API concentration monitoring within a Continuous Direct Compression (CDC) process, using a Feed Frame Simulator (FFSIM). Both probes simultaneously measured moving powder under dynamic conditions to assess their modelling performance. Instrument settings, including the number of spectral averages, were selected to ensure the consistent measurement of a unit-dose for both instruments. The resulting datasets were processed and Partial Least Squares (PLS) models were built. Root Mean Square Error (RMSE) values indicate that NIR-SRS performed comparably to NIR, resulting in similar error values and marginally higher concentration detection limits; however, its narrower wavelength range currently limits its suitability for drug loading quantification and modelling, particularly for low-dose formulations where broader spectral coverage is critical to enhance model robustness and sensitivity.