Characterization of Near Infrared and Raman Spectroscopy for In-line Monitoring of Low-Drug Load Formulation in Continuous Manufacturing Process

Reflectance spectroscopy is an excellent candidate for process analytical technology (PAT) applications in continuous manufacturing of pharmaceutical tablets. Spectroscopic methods provide a real-time, nondestructive measurement of the active pharmaceutical ingredient (API) concentration in order to ensure product quality and uniformity. Of particular challenge is the powder blends with low drug loads (<5% w/w) where the measurement of the signal-to-noise and, in turn, precision limit the ability of the method. We evaluate both near-infrared (NIR) and Raman spectroscopy for use in PAT applications by measuring pharmaceutical blends of varying active ingredient concentrations. Both spectrometers are equipped with a fiber-optically coupled probe head for noncontact measurement of powder blends. A mockup of the interface between the spectrometer and powders within the feed frame of a rotary tablet press is used to simulate the movement of powder blends from the mixer to the press. A port on the feed frame al...