Hybrid model development and nonlinear model predictive control implementation for continuous dry granulation process

This study focuses on the development of a hybrid model to integrate roll compaction and ribbon milling operations to design and control a continuous dry granulation process. The proposed hybrid model has three features: (1) it compensates for underestimated roll gap measurements with knurled rolls, (2) it represents the bimodal size distribution of granules using five fitting parameters of the bimodal Weibull distribution instead of only using specific size percentiles, and (3) it considers the impact of rotor-screen gaps on granules. Furthermore, the hybrid model facilitates the implementation of nonlinear model predictive control in a roller compactor Alexanderwerk WP120. Compared to widely applied open-loop operations in the pharmaceutical industry, nonlinear model predictive control demonstrates better performance, indicated by lower integral absolute errors in controlling mass throughput and ribbon solid fraction, in which real-time measurements can be obtained using a near-infrared sensor and a novel spectra selection approach.