(401e) Design and Implementation of An Efficient Control System in a Continuous Pharmaceutical Manufacturing Process Via Roller Compaction

Pharmaceutical industries are facing enormous challenges to achieve the predefined end product quality consistently as well as to satisfy the regulatory constraints, flexible market demands, operational complexities and economical limitations [1]. A novel manufacturing strategy based on continuous processing integrated with online monitoring tools coupled with efficient automatic feedback control system is therefore highly desired [2]. However, because of different level of complexities involved (e.g. solid handling, irregular flow, multi-variate interactions, difficulty in real time measurement) in addition to the requirement of very precise product quality, the design and implementation of an efficient control system in the pharmaceutical manufacturing involving the solid dosage form is still a challenging task. The process involving the solid flow is not as simple to control as the process involving the liquid/gas flow therefore the conventional control strategy may not be efficient, although it could be adapted. The design and implementation of the process control system involves the identification of critical control variables, coupling of the control variables with suitable actuators, selection of suitable monitoring tools, selection of control strategy followed by controller parameters tuning, model-based closed-loop performance evaluation and finally implementation to the manufacturing plant through the available hardware (e.g. Delta V) and control interface (e.g. OPC).

In the work reported here, an efficient control system for an integrated continuous pharmaceutical tablet manufacturing process via roller compaction has been designed. The continuous manufacturing process consists of the following unit operations: blending, roller compaction, milling, tablet compression and coating. The roller compactor has been used as a means of dry granulation to avoid any API water sensitive issues involved. The designed control system consists of four cascade control loops and three single control loops giving 36 tuning parameters. An effective controller parameter tuning strategy involving ITAE methods coupled with an optimization strategy has also been proposed. The designed control system has been implemented in a first principle model-based flowsheet simulated in gPROMS (Process System Enterprise) to verify its performance and is being implemented in a continuous pilot plot at Rutgers University. The systematic methodology for pharmaceutical process control system design as well as supporting process models and knowledge/data base has also been developed.

The objective of this presentation is two-fold: first to highlight the design of control system for a continuous tablet manufacturing process with roller compaction, and second to demonstrate the performance of the designed control system through the first principle model as well as in a pilot plant.

References

[1] Singh, R., Gernaey, K. V., Gani, R., (2010). ICAS-PAT: A Software for Design, Analysis & Validation of PAT Systems. Computers & Chemical Engineering, 34(7), 1108-1136.

[2] Ramachandran, R., Arjunan, J., Chaudhury, A, Ierapetritou, M. (2012). Model-Based Control Loop Performance Assessment of a Continuous Direct Compaction Pharmaceutical Processes. J. Pharm. Innov., 6(3), 249-263.