Integrated modeling of a continuous direct compression tablet manufacturing process: A production scale case study

A flowsheet model for a continuous direct compression tableting process is developed and applied to process data generated at production scale. The model contains powder feeding, blending and tablet compaction unit operations. The dataset was provided by Merck & Co., Inc., Kenilworth, NJ USA using a GEA ConsiGma™ continuous direct compression process designed for approximately 50 kg/h throughput using a six ingredient, potentially commercial, formulation. A tanks-in-series methodology is used to model the transport of powders through the blending units and a number of tablet compaction equations are selectable which can illustrate how upstream changes in composition are propagated to tablet properties. The flowsheet model performed well based on the available dataset with accurate predictions of API concentration and tablet hardness. Monte Carlo simulations were used along with the flowsheet model to investigate the contribution of feeder flowrate variability to measurement noise and the sensitivity of tablet hardness to process parameters and material properties. [Display omitted] •Tanks in series approach provides simple and accurate residence time model results.•Model performed well over a wide range of operating conditions.•Flowsheet model could simulate realistic failure modes for risk assessment purposes.•Impact of process parameters and material properties were investigated.•Process parameters more significant than material properties for tablet compaction.