(438e) Closed Loop Dynamics of Ribbon Density in a Dry Granulation Process
AIChE Annual Meeting
2017 Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Multivariate Modeling and Quality-by-Control Approaches for Pharmaceutical Processes
Tuesday, October 31, 2017 - 4:43pm to 5:05pm
Dry granulation is an inherently continuous process. The particle size distribution and bulk density of the granules are critical quality attributes of the process, which depend primarily on the ribbon relative density. The ribbon density is hence a crucial intermediate quality attribute of the unit operation. It is thereby valuable to monitor and control the ribbon density for ensuring desired granule qualities.
Assurance of product quality in real-time requires satisfactory process models with a robust sensor network and control architecture. A dynamic, simplified process model along with real-time monitoring capability is important to the implementation of supervisory control of the process to achieve Quality by Control.
The Johanson model  describes the fundamental solid mechanics of roller compaction as a standalone steady state process. FEM analyses have suggested modifications to the model for improved prediction of ribbon density . A process scale model, however, needs to consider the production rate and requires integration of previous unit operations that feed into the roller compactor, in addition to the solid mechanics of the roller compactor.
The process model by Reynolds et al  integrates the screw conveyor with the roller compaction system, describing the effect of screw speed on the ribbon density and production rate at steady state. A dynamic process model is, however, essential for the implementation of a control system, as proposed by Hsu et al . The model did not include the flow rates through the system and lacked experimental validation.
This work focuses on a modified process model incorporating the solid mechanics, process dynamics and throughput. The model combines the dynamics of material flow from Hsu et al (2010a) and Reynolds et al (2010) and solid mechanics suggested by Liu and Wassgren (2016). Demonstration of real-time ribbon density monitoring using NIR and microwave sensors [6,7] enable the validation of such a dynamic model. Additionally, the model evaluates the integrated system of a hopper and screw conveyor feeding into the roller compactor.
Blends comprising of acetaminophen and microcrystalline cellulose at inlet flow rates of 8-12 kg/h and varying roll pressures are used for real-time monitoring of ribbon density. The solid mechanics material parameters are estimated using ribbons. The process variables and ribbon density are recorded and monitored using DeltaV DCS.
This work progresses to demonstrate the implementation of ribbon density as proposed by Hsu et al. The integrated process model and real time ribbon density monitoring enable the development of control strategies for the desired ribbon density and eventually the granule properties.
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