Plant-Wide Control of a Continuous Tablet Manufacturing for Quality-By-Design Based Pharmaceutical Manufacturing

Abstract

Abstract The pharmaceutical industry is strictly regulated, where precise control of the end product quality is necessary to ensure the efficiency of the drug products. In this work, a combined feed-forward/feedback (FF/FB) control system has been developed for a direct compaction continuous tablet manufacturing pilot-plant. The feed-forward controller takes into account the effect of process disturbances and raw material variability proactively while the feedback control system ensures the end product quality consistently. The feed-forward control loop is based on real time monitoring of the powder bulk density while the feedback control loops are based on the powder level of instrumented hopper, drug concentration, tablet weight and hardness. Powder blend density has significant effects on the end product quality of the pharmaceutical tablets and therefore has been selected as the feed-forward variable. The coupled FF/FB control system ensures minimum variability in the final product quality irrespective of process and raw material variations.