(697a) Implementation of a Reduced System Model to a Continuous Direct Compression Manufacturing Process
AIChE Annual Meeting
2015
2015 AIChE Annual Meeting Proceedings
Pharmaceutical Discovery, Development and Manufacturing Forum
Model Based Integrated Design of Pharmaceutical Drug Substance and Drug Product Processes II
Thursday, November 12, 2015 - 12:30pm to 12:50pm
The continuous direct compression manufacturing process consists of several loss-in-weight (LIW) feeders, a horizontal mixer, a surge hopper, and tablet press equipped with a near infrared (NIR) probe at the die-filling station of the tablet feed frame. A system-wide deterministic dynamic model was used to fit dispersion coefficients within the various elements for a given formulation/throughput using the feed frame NIR to measure the system response. This partial differential non-linear algebraic system model consisting of ~8,000 equations is sufficiently complex that it cannot be solved real-time with the current technology. This necessitates a second, reduced system model based upon the original deterministic model and uses thousands of digital experiments to create a set of response surfaces. The result is a data-driven version of the model that can be executed real-time using a PAT controller (e.g. SynTQ) to assess the impact of feeder variability on the final product within the distributed control system (e.g. DeltaV). The real-time reduced system model provides prediction of the feed frame concentration, the time when a disturbance will reach the die-filling station, and the time when the disturbance will clear the system.