(697f) Dynamic Modeling and Advanced Control of Tablet Press

The tablet press is one of the most critical but least understood unit operation involved in both batch and continuous tablet manufacturing process. Various operations that take place simultaneously in a tablet press, including flow in a chute or a hopper, feeding of powder blend/granules into dies via feed frame, and tablet compression, are characterized by complex phenomena that are difficult to model. Moreover, the control system of existing tablet presses has not changed much in several decades and needs to be improved significantly. For example, with current state of the art techniques and tools, the tablet weight and the tablet hardness can not be controlled simultaneously in real time and raw materials and process variability can not be mitigated proactively. Powder raw material characteristics, feeder level, shear history, upstream milling and blending operation, and powder transport can all have significant impact on powder bulk density, flowability, and lubricity and thereby on critical tablet quality attributes. Therefore, dynamic modeling to understand tablet press performance, and an advanced control system is highly desirable. The Rutgers continuous pharmaceutical manufacturing platform provides an opportunity to improve the tablet press control system by allowing integration of meaningful real time measurements with feed-forward and feedback control systems.

In this work, dynamic models of tablet press, including a detailed feed frame model as well as a compression model, are developed and applied for the design of an advanced control system. The feed frame operation can have significant impact on powder mixing and die filling and thereby on critical quality attributes such as tablet weight, hardness, dissolution and API potency. One of the objectives of feed frame modeling was therefore to provide a predictive tool to understand the complex mixing and segregation phenomena occurring at this stage and to understand tablet die feeding behavior. The integrated tablet compression model will then allow studying the effects of feed frame speed and raw material properties on critical quality attributes. The tablet press model is integrated with the direct compaction line to study the effects of feeding, milling and blending effects on critical quality attributes. The developed mechanistic dynamic model has been employed to design an advanced tablet press control system and to evaluate its performance prior to implementation to the pilot-plant situated at Rutgers University. First, the feedback tablet weight and hardness control loops are decoupled so that these variables can be controlled independently and simultaneously. Then a feed-forward control loop is integrated with the feedback control loops to take the proactive mitigation actions based on powder bulk density variability.

The objective of this presentation is to demonstrate the dynamic model of tablet press, and to illustrate its applicability for design and evaluation of advanced tablet press control system.