In-Line Blend Potency Measurements of Low-Dose Formulations Using a Novel Deep-UV LIF Probe in the Feed Frame of a Rotary Tablet Press

Abstract

The increasing demand for nondestructive quantification of active pharmaceutical ingredients in low-dose formulations has highlighted the sensitivity limitations of existing in-line process analytical technology tools. This study integrates a deep-UV light-induced fluorescence (LIF) sensor into the feed frame of a rotary tablet press for in-line monitoring of blend potency.

Two five-component, low-dose model formulations containing caffeine or indomethacin were evaluated. Partial Least Squares (PLS) regression was used to calibrate models based on spectra collected across a range of blend potencies (0.65 to 1.35%_w/w), three paddle speeds, and two filler ratios. Instrument-related variability was assessed through verification runs at 1.00%_w/w drug load using a second LIF spectrometer prototype. Step-change experiments (1.00% → 0.90% → 1.10%_w/w) were conducted to evaluate model performance for the two instruments.

Results showed that higher paddle speeds and increased formulation density enhanced LIF response. Instrument-to-instrument and day-to-day variability were observed but were mitigated through chemometric modeling. After evaluating development and performance metrics, the LIF sensor demonstrated adequate sensitivity and robust performance, supporting its potential application as an in-line PAT tool for the continuous manufacturing of low-dose formulations.

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In-Line Blend Potency Measurements of Low-Dose Formulations Using a Novel Deep-UV LIF Probe in the Feed Frame of a Rotary Tablet Press, Louis Bouckaert, Rohit Bhartia, Zhenqi Shi, Ray Reid, Ken Nguyen, Jason Micklewright, William Hug, Andrew Anderson, Tom Van Den Kerkhof, Mario Hellings, Philip Deamer, Ke Hong, Peter Brush, Tomas Vermeire, Dong Xiang, Gregory Doddridge, Gordon Lambertus, Denilson Mendes de Oliveira, Chris Vervaet, Valérie Vanhoorne, and Thomas De Beer, Analytical Chemistry Article ASAP, DOI: 10.1021/acs.analchem.5c06314