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

• This study showed the first experimental NMPC implementation in a roller compactor. • The bimodal size distribution of granules can be controlled using NMPC. • Bimodal Weibull distribution can be used to describe the granule size distribution. • A novel NIR spectra analysis approach was used to measure ribbon solid fraction. • A hybrid model is developed to integrate roll compaction and ribbon milling processes. 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. [ABSTRACT FROM AUTHOR]