Experimental implementation of a Quality-by-Control (QbC) framework using a mechanistic PBM-based nonlinear model predictive control involving chord length distribution measurement for the batch cooling crystallization of l-ascorbic acid

• Published in: Chemical engineering science 2019-02, Vol.195, p.335-346
• Main Authors: Szilágyi, Botond, Borsos, Ákos, Pal, Kanjakha, Nagy, Zoltán K.
• Format: Article
• Language: English
• Subjects: Ascorbic acid; DNC; NMPC; Population balances; QbC; Quality-by-Control
• ISSN: 0009-2509; 1873-4405
• DOI: 10.1016/j.ces.2018.09.032

•l-ascorbic acid crystallization is investigated from aqueous solution.•The crystallization kinetics is estimated from batch experiments based on concentration and CLD data.•FBRM is used for the first time as quantitative in-line sensor in the predictive control system.•Model-free Quality-by-Control (QbC) based on DNC is compared with model-based QbC using the proposed NMPC. l-ascorbic acid is synthetized in large industrial scale from glucose and marketed as an immune system strengthening agent and anti-oxidant ingredient. The overall yield of conversion of the precursor glucose to l-ascorbic acid is limited, therefore the crystallization is a critically important step of the l-ascorbic acid production from economic point of view. It is widely accepted that the crystal size distribution (CSD) influences numerous relevant macroscopic properties of the final crystalline product and it also significantly affects the downstream operations. The present paper discusses the chord length distribution (CLD, which is directly related to the CSD) control, during the crystallization of l-ascorbic acid from aqueous solution. Batch crystallization process is employed, which is the classical, and still dominant, operation in fine chemical and pharmaceutical industries. A comparative experimental study of two state-of-the-art Quality-by-Control (QbC) based crystallization design approaches are presented: (1) a model-free QbC based on direct nucleation control (DNC) and (2) a model-based QbC using a novel nonlinear model predicative control (NMPC) framework. In the first investigation, the DNC, a process analytical technology based state-of-the-art model free control strategy, is applied. Although, DNC requires minimal preliminary system information and often provides robust process control, due to the unusual crystallization behavior of l-ascorbic acid, it leads to long batch times and oscillatory operation. In a second study the benefits of model-based QbC approach are demonstrated, based on using a NMPC approach. A population balance based crystallization process model is built and calibrated by estimating the nucleation and growth kinetics from concentration and CLD measurements. A projection based CSD to CLD forward transformation is used in the estimation of nucleation and growth kinetics. For robustness and adaptive behavior, the NMPC is coupled with a growing horizon state estimator, which is aimed to continuously improve the model by re-adjusting the kinetic cons