(342b) Flowsheet Modeling of a Continuous Direct Compression Process at Production Scale

A flowsheet model for a continuous direct compression and tablet coating and drying process is developed and applied to process data generated at production scale. The flowsheet model contains feeding, blending, tablet compaction and tablet coating and drying units. The model is constructed using gSOLIDS process modelling software (PSE Ltd). The feeding units are assumed to have a constant flowrate, the blending units are based on a tanks-in-series (TIS) methodology and the tablet press model produces tablet hardness as a critical quality attribute. A thermodynamic model for the coating and drying process considers mass and energy conversation to describe five segregated sub-processes (loading, preheating, coating, drying and discharging). Process data is collected by Merck & Co using a GEA Group (AG) continuous direct compression and coating and drying process designed for a six ingredient formulation. Parameter estimation is used determine the mean residence time and lag time for the tanks in series representing the blending process. A number of tablet porosity models are added to the tablet press model increasing model accuracy and flexibility. The coating and drying model describes the process exhaust temperature and relative humidity within a relative error of 2.5%. The flowsheet model performs well using the existing data set and will be used for further process optimization as the process approaches commercial production. In addition, the model is used to investigate process variability in the feeding flowrate and compaction force of the tablet press. A major application of the model is to be used in conjunction with process analytical technology (PAT) for process control.