Adaptive MIMO neuro-fuzzy logic control of a seeded and an unseeded anti-solvent semi-batch crystallizer
ABSTRACT This study explores the implementation of a two input/two output adaptive neuro-fuzzy logic controller on an anti-solvent semi-batch crystallization process. The solution concentration and the solubility curve of paracetamol (PA) in a mixture of water and isopropanol in the range of temperatures between 10 and were determined using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy. The in situ chord length distribution of crystals was obtained from laser backscattering by focus beam reflectance measurement (FBRM) probe. The controlled variables were the supersaturation and the difference in the chord length counts between two sampling times, and the manipulated variables were the cooling rate and anti-solvent flow rate. The ‘direct’ objectives of this study were to keep the controlled variables inside their predetermined ranges. The ‘indirect’ objectives were to improve the end-of-batch properties that included batch time, yield, and particle size distribution. Performance of the adaptive neuro-fuzzy logic controller for the closed-loop system was evaluated based on meeting the ‘direct’ and ‘indirect’ objectives. The best results in terms of batch time and product yield for unseeded experiments were 280 min and 95%, respectively. However, the most significant improvement was noted in the seeded set of experiments that resulted in 225 min batch time, an increase of the volume weighted mean size by , and 99% product yield.
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ABSTRACT: Recent advances in in situ measurement technology and automation of batch crystallizers have enabled the development of batch crystallization recipes in which the desired supersaturation profile is followed by feedback control. This paper describes a new approach for following supersaturation setpoints for antisolvent crystallizations that is easy to implement for the tried crystallization. Simulations and application to a proprietary drug compound demonstrate how this combination of automation and in process measurements enables the rapid development of batch crystallization processes in the pharmaceutical industry.Crystal Growth & Design - CRYST GROWTH DES. 01/2006; 6(4).
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ABSTRACT: Crystallization is the main separation and purification process for the manufacturing of drug substances. Not only does crystallization affect the efficiency of downstream operations such as filtering, drying, and formulating, the efficacy of the drug can be dependent on the final crystal form. Advances in simulation and control algorithms and process sensor technologies have enabled the development of systematic first-principles and direct design approaches for the batch control of crystallization processes. These approaches address different challenges associated with pharmaceutical crystallization control. This paper provides an overview of recent technological advances in the in situ control of pharmaceutical crystallization processes. Implementation of the first-principles and direct design approaches are compared, and their relative merits are explained. Areas of future opportunities for application of advanced control strategies in pharmaceutical crystallization are presented.Journal of Process Control. 01/2005;
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ABSTRACT: This paper presents a personal, thus necessarily subjective, view of the operation of batch and semi-batch reactors. The emphasis is on safety, product quality and scale-up. Key characteristics of discontinuous reaction systems are discussed, along with the resulting implications for monitoring, control and optimization. The industrial needs are compared with the research solutions proposed by academia. It is argued that, in industry, measurement and modeling issues are often more important than the algorithmic aspects related to the computation of control and optimization strategies. Major challenges and selected research opportunities are discussed.Journal of Process Control. 01/1998;