(451e) Investigating Effects of Dynamic Process Variability in Continuous Direct Compression on Tablet Quality Attributes through a Science-Based Digital Twin
AIChE Annual Meeting
2019
2019 AIChE Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Continuous Processing Technologies Applied in Drug Product Manufacturing
Wednesday, November 13, 2019 - 8:57am to 9:16am
font-family:" times new roman>Continuous direct compression (CDC) is
emerging as a common platform for continuous tablet manufacturing. In a CDC
line, several sources of process variability are introduced through individual
unit operations, including feeder flow rates (both due to refill events and
higher frequency noise), micromixing of the blend, and tablet press flow and
die filling behavior. These dynamic disturbances can influence the final tablet
composition, porosity, strength, and mass.
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font-family:" times new roman>In this work, the combined effects of
dynamic sources of process variability on tablet quality attributes will be
investigated through a science-based digital twin encompassing loss-in-weight
feeders, refill units, continuous blenders, a surge hopper, a feed frame, and a
tablet press, shown as a flowsheet model in Figure 1. Model validation
requirements and workflows for the loss-in-weight feeder and continuous blender
will be presented, and the impact of feeder control modes and settings will be
explored. The significance of the height of the material in the surge hopper on
disturbance propagation will be demonstrated. Dynamic variability in the tablet
press will be introduced through variations in blend composition and bulk
density in the die. The tablet-to-tablet variability in quality attributes will
be quantified as distributions in quality attributes as predicted by the model
for the tablet tester. The implications for process risk assessment and
mitigation and process control strategies will be discussed.
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Figure 1:
Flowsheet model of continuous direct compression line, including five feeders,
two blenders, a surge hopper, feed frame, and tablet press and associated
sensors. Results figures show fluctuations in feeder flow rates and blend
composition throughout the system in response to disturbances.