Improving of Crystal Size Distribution Control Based on Neural Network-Based Hybrid Model for Purified Terephthalic Acid Batch Crystallizer

A main difficult task in batch crystallization is to control the size distribution of crystal products. Complexity and highly nonlinear dynamic behavior directly affect to model-based control strategies which heavily depend on the rigorous knowledge of crystallization. In this work, neural network-based model predictive control and inverse neural network control strategies are proposed and integrated with an optimization based on neural network-based hybrid model to control temperatures of a purified terephthalic acid batch crystallizer. A neural network-based hybrid model of the batch crystallizer is developed to provide nonlinear dynamic responses used in optimization algorithm for finding an optimal temperature profile related to the quality of a crystal product. Then, the obtained optimal profile is used as set points of the proposed control strategies for improving the crystal product quality. The performances and robustness of the proposed controllers are evaluated in several cases such as for set point tracking and plant/model mismatches. Simulation results show that the neural network-based model predictive control gives the best control performance among the inverse neural network control and a conventional PID controller in all cases.A main difficult task in batch crystallization is to control the size distribution of crystal products. Complexity and highly nonlinear dynamic behavior directly affect to model-based control strategies which heavily depend on the rigorous knowledge of crystallization. In this work, neural network-based model predictive control and inverse neural network control strategies are proposed and integrated with an optimization based on neural network-based hybrid model to control temperatures of a purified terephthalic acid batch crystallizer. A neural network-based hybrid model of the batch crystallizer is developed to provide nonlinear dynamic responses used in optimization algorithm for finding an optimal temperature profile related to the quality of a crystal product. Then, the obtained optimal profile is used as set points of the proposed control strategies for improving the crystal product quality. The performances and robustness of the proposed controllers are evaluated in several cases such as for set point tracking and plant/model mismatches. Simulation results show that the neural network-based model predictive control gives the best control performance among the inverse neural network control and a conventional PID controller in all cases

Neural Network Based Modeling and Control for a Batch Heating/Cooling Evaporative Crystallization Process

Crystallization processes have been widely used for separation in many fields to provide a high purity product. In this work, dynamic optimization and neural network (NN) have been applied to improve the quality of the product: citric acid. In the dynamic optimization, optimization problems maximizing both crystal yield and crystal size have been formulated. The neural networks have been developed to provide NN models to be used in the formulation of not only neural network inverse control (NNDIC) but also neural network model predictive control (NNMPC) strategies. The Levenberg Marquadt algorithm has been used to train the network and optimal neural network architectures have been determined by a mean squared error (MSE) minimization technique. In addition, a neural network model has been designed to provide estimates of the temperature and the concentration of the crystallizer. These estimates have been incorporated into the NNMPC controller. In the NNDIC controller, another neural network model has been applied to predict the set point of jacket temperature. The simulation results have shown that the obtained crystal size is increased by 19% and 30% compared to that by cooling and evaporation methods respectively and the obtained yield is increased more than 50%. The robustness of the proposed controller is investigated with respect to parameters mismatches. The results have shown that the NNMPC controller provides superior control performances in all case studies

A Model-based Framework to Control the Crystal Size Distribution

Crystallization is an old unit operation in the industry which is widely used as a separation process due to its ability to produce highly valued chemical with high purity. Despite the long history of batch crystallization, industry still relies on rule of- thumb techniques for their crystallization processes. Thus, any method to improve the products characteristics such as size and morphology will be highly valued. Advances in robustness and accuracy of automated in situ sensors give the possibility to move towards an engineering based approach by implementing the real-time monitoring and control of the process. The research undertaken here investigates the development of an advanced framework for the operation of crystallization processes. This project builds upon the synergy among the research teams at LSU and at the University of Cagliari. The proposed methodology comprises of exploiting an advanced model to simulate the process, On-line implementation of the image-based approach within a feedback loop in a completely automated feedback fashion and implementation of model-free control technology. In situ measurement of crystals’ size distribution by using image-based technique and wavelet-fractal algorithm is implemented in a real-time environment for inferring the particles characteristics captured at different time of the experiment. This technique is becoming increasingly more attractive due to availability of high speed imaging devices and powerful computers at reasonable costs and the adaptability to real time application. The process is modelled by means of a stochastic approach. This is an alternative method to the traditional population balance which leads to a more straightforward model that can be solved analytically and obtain the CSD over time. The simplicity of the model gives the possibility to properly implement an automatic control strategy

Hybrid Neural Network Controller Design for a Batch Reactor to Produce Methyl Methacrylate

Methyl methacrylate (MMA) production in an exothermic batch reactor provides a challenging problem for studying its dynamics behavior and temperature control. This work presents a neural network forward model (NN) to predict a concentration of methyl methacrylate, a jacket temperature and temperature profile in the reactor. An optimal NN model has been employed to predict state variables incorporating into a model predictive control (MPC) algorithm to determine optimal control actions. To control the temperature, neural network based control approaches: a neural network direct inverse control (NNDIC) and a neural network based model predictive control (NNMPC) have been formulated. In addition, a dynamic optimization approach has been applied to find out an optimal operating temperature to achieve maximizing the MMA product at specified final time. Simulation results have indicated that the NNMPC is robust and gives the best control results among the PID and NNDIC in all cases

Non-Classical Nucleation Phenomena Study And Following Process Monitoring and Optimization in Solution Crystallization Process

Nucleation is a crucial step in the solution crystallization process. Despite their good development, classical nucleation theory and two-step nucleation theory cannot explain all the nucleation phenomena, especially for the non-classical nucleation phenomena which include oiling out, gelation and non-monotonic nucleation. Accordingly, for the non-classical nucleation systems, the crystallization processes are seldom designed based on the nucleation monitoring and supervision. In this thesis, crystallization process optimization was conducted to study the mechanism of non-classical nucleation phenomena and in-line process monitoring technology development. Two kinds of non-classical nucleation phenomena with non-monotonic nucleation rate and gel formation were investigated, and accordingly, two nucleation pathways that self-induced nucleation and jellylike phase mediated nucleation were proposed based on the analysis of in-line spectral monitoring and off-line sample characterizations. Results indicated the agitation level would affect the pre-nucleation clusters’ existence in the non-monotonic nucleation system, and the properties of solvent determined the formation of jellylike phase and the transformation to crystals. Motion-based objects tracking model and the state-of-the-art neural network Mask R-CNN were introduced to monitor the onset of nucleation and following the crystallization process. Combined with a cost-effective camera probe, the developed real-time tracking system can detect the nucleation onset accurately even with ultrasonic irradiation and can extract much more information during the whole crystallization process. Subsequently, ultrasonic irradiation and seeding were used to optimize a non-classical nucleation system that accompanied oiling out phenomenon. Different frequencies and intensities of ultrasonic irradiation and seeds addition time were screened to optimize the nucleation step, which proved their effectiveness of promoting nucleation and narrowing the metastable zone widths of oiling out and nucleation. A fine-tuning of nucleation step was carried out in a mixed suspension mixed product removal (MSMPR)-tubular crystallizer series. The nucleation step was optimized in the MSMPR stage with the aid of principal component analysis, which enabled the growth of crystals in the tubular crystallizer with preferred polymorphism, shape, and size. The study in this thesis provides insights into non-classical nucleation mechanism and nucleation based crystallization process design and optimization

A Model-Centric Framework for Advanced Operation of Crystallization Processes

Crystallization is the main physical separation process in many chemical industries. It is an old unit operation which can separate solids of high purity from liquids, and is widely applied in the production of food, pharmaceuticals, and fine chemicals. While industries in crystallization operation quite rely on rule-of-thumb techniques to fulfill their requirement, the move towards a scientific- and technological- based approach is becoming more important as it provides a mechanism for driving crystallization processes optimally and in more depth without increasing costs. Optimal operation of industrial crystallizers is a prerequisite these days for achieving the stringent requirements of the consumer-driven manufacturing. To achieve this, a generic and flexible model centric framework is developed for the advanced operation of crystallization processes. The framework deploys the modern software environment combined with the design of a state-of-the-art 1-L crystallization laboratory facility. The emphasis is on developing an economically and practically feasible implementation which can be applied for the optimal operation of various crystallization systems by pharmaceutical industries. The key developments in the framework have occurred in three broad categories: i. Modeling: Using an advanced modeling tool is intended for accurate representation of the behavior of the physical system. This is the cornerstone of any simulation, optimization or model-based control approach. ii. Monitoring: Applying a novel image-based technique for online characterization of the particulate processes. This is a promising method for direct tracking of particle size and size distribution with high adaptability for real-time application iii. Control: Proposing numerous model-based strategies for advanced control of the crystallization system. These strategies enable us to investigate the role of model complexity on real-time control design. Furthermore, the effect of model imperfections, process uncertainty and decision variables on optimal operation of the process can be evaluated. Overall, results from this work presents a robust platform for further research in the area of crystal engineering. Most of the developments described will pave the way for future set of activities being targeted towards extending and adapting advanced modeling, monitoring and control concepts for different crystallization processes

Modelling and control of combined cooling and antisolvent crystallization processes

Although for decades nearly all pharmaceuticals have been purified by crystallization, there have been a disproportionate number of problems associated with the operation and control of these processes. This paper provides an overview of the recent advances in model-based and model-free (direct design) approaches to control the crystallization of pharmaceuticals, treating both antisolvent and cooling crystallization. A model-based combined technique which simultaneously controls the antisolvent addition rate and the cooling profile is presented. A population balance model of the combined cooling-antisolvent addition system is developed and a moments model is used in optimal control strategies with various objective functions. The simulation and experimental results show the advantages of the combined approach

Modeling, optimization, and sensitivity analysis of a continuous multi-segment crystallizer for production of active pharmaceutical ingredients

We have investigated the simulation-based, steady-state optimization of a new type of crystallizer for the production of pharmaceuticals. The multi-segment, multi-addition plug-flow crystallizer (MSMA-PFC) offers better control over supersaturation in one dimension compared to a batch or stirred-tank crystallizer. Through use of a population balance framework, we have written the governing model equations of population balance and mass balance on the crystallizer segments. The solution of these equations was accomplished through either the method of moments or the finite volume method. The goal was to optimize the performance of the crystallizer with respect to certain quantities, such as maximizing the mean crystal size, minimizing the coefficient of variation, or minimizing the sum of the squared errors when attempting to hit a target distribution. Such optimizations are all highly nonconvex, necessitating the use of the genetic algorithm. Our results for the optimization of a process for crystallizing flufenamic acid showed improvement in crystal size over prior literature results. Through the use of a novel simultaneous design and control (SDC) methodology, we have further optimized the flowrates and crystallizer geometry in tandem.^ We have further investigated the robustness of this process and observe significant sensitivity to error in antisolvent flowrate, as well as the kinetic parameters of crystallization. We have lastly performed a parametric study on the use of the MSMA-PFC for in-situ dissolution of fine crystals back into solution. Fine crystals are a known processing difficulty in drug manufacture, thus motivating the development of a process that can eliminate them efficiently. Prior results for cooling crystallization indicated this to be possible. However, our results show little to no dissolution is used after optimizing the crystallizer, indicating the negative impact of adding pure solvent to the process (reduced concentration via dilution, and decreased residence time) outweighs the positive benefits of dissolving fines. The prior results for cooling crystallization did not possess this coupling between flowrate, residence time, and concentration, thus making fines dissolution significantly more beneficial for that process. We conclude that the success observed in hitting the target distribution has more to do with using multiple segments and having finer control over supersaturation than with the ability to go below solubility. Our results showed that excessive nucleation still overwhelms the MSMA-PFC for in-situ fines dissolution when nucleation is too high