NCO-tracking based control of semi-batch antisolvent crystallization processes in the presence of uncertainties

Control of crystallization processes in order to obtain desired product specifications is very critical in pharmaceutical industries, as it influences not only the efficiency of the other downstream processes but also the bioavailability of the drug. Hence, motivated to counter the pragmatic limitations of implementing the optimal control policies in the presence of plant-model mismatch, measurement-based optimization (MBO) schemes for real-time optimal operation of (semi-)batch pharmaceutical antisolvent crystallization processes has been presented in this paper. MBO schemes are based on tracking the Necessary Conditions of Optimality (NCO), usually a sequence of boundary and (or) interior arcs, using measurement feedback. The current study explores this approach by designing neighboring extremal (NE) controller to follow the optimal trajectory in the interior arcs during the real-time optimal control. Furthermore, performance assessment of the NE controller is done by comparing to different control strategies for various scenarios of plant model mismatch.