Modelling and control approaches for a continuous powder to tablet manufacturing process

The pharmaceutical industry is moving towards continuous manufacturing to improve efficiency, reduce waste and improve product quality. Tablets are the most common form of pharmaceutical products and is therefore important to understand their continuous manufacturing. A Consigma-25 powder to tablet line via wet granulation was used as is a good example of a continuous production line.
The impact of the granulation parameters such as the L/S ratio and filling times on the behaviour of the granules throughout the drying process was investigated. The water mass was found to be the only driver of the drying time required to reach a specific moisture content when the drying conditions were kept constant.
The impact of both the granule moisture content after drying and L/S ratio on the granule compression properties and final tablet properties was investigated. The compactability of the granules remained unchanged while the compressibility was affected by both variables. Both an increase in L/S ratio and moisture content lead to denser and stronger tablets. The dissolution time of the tablets was found to be a function of the tablet porosity with the value increasing exponentially as the porosity got closer to 0.
The data obtained was used to fit flowsheet models for both the drying and compaction processes. The models performed well and were used to develop, tune and test different control methods. A feed forward control loop that maintained the output granule moisture content after the dryer by varying the drying time performed well when tested with random liquid flow variability. Feedback, feed forward and model predictive controllers to control the tablet properties were developed and tested. The controllers worked well showcasing the importance of control during continuous manufacturing and the advantages of models during the development process.