Powder composition monitoring in continuous pharmaceutical solid-dosage form manufacturing using state estimation - Proof of concept

Abstract

In continuous solid-dosage form manufacturing, the powder feeding system is responsible for supplying downstream the correct formulation of the drug product ingredients. The composition of the powder delivered by the feeding system is inferred from the measurements of powder mass flow from the system feeders. The mass flows are, in turn, inferred from the loss in weight measured in the feeder hoppers. Most loss-in-weight feeders post-process the mass flow signal to deliver a smoothed value to the user. However, such estimated mass flows can exhibit a low signal-to-noise ratio. As the feeders are critical elements of the control strategy of the manufacturing line, better instantaneous estimates of mass flow are desirable for improving the quality assurance. In this study, we propose a model-based approach for monitoring the composition of the powder fed to a continuous solid-dosage line. The monitoring system is based on a moving-horizon state estimator, which carries out model-based reconciliation of the feeder mass measurements, thus enabling accurate composition estimation of the powder mixture. Experimental datasets from a direct compression line are used to validate the methodology. Results demonstrate improvement with respect to current industrial solutions.

Keywords: Continuous pharmaceutical manufacturing; Loss-in-weight feeder; Powder feeder; Quality-by-design; Soft sensing; State estimation.