Abstract
Crystallization is one of the important unit operations for the separation and purification of solid products in the chemical, pharmaceutical, and pesticide industries, especially for realizing high-end, high-value solid products. The precise control of the solution crystallization process determines the polymorph, crystal shape, size, and size distribution of the crystal product, which is of great significance to improve product quality and production efficiency. In order to develop the crystallization process in a scientific method that is based on process parameters and data, process analysis technology (PAT) has become an important enabling platform. In this paper, we review the development of PAT in the field of crystallization in recent years. Based on the current research status of drug crystallization process control, the monitoring methods and control strategies of feedback control in the crystallization process were systematically summarized. The focus is on the application of model-free feedback control strategies based on the solution and solid information collected by various online monitoring equipment in product engineering, including improving particle size distribution, achieving polymorphic control, and improving purity. In this paper, the challenges of feedback control strategy in the crystallization process are also discussed, and the development trend of the feedback control strategy has been prospected.
Highlights
Crystallization is an important unit operation in major sectors of the chemical process and allied industries
The results show that concentration feedback control can reduce the particle size distribution of crystal products, it has no significant effect on the product purity, and in contrast, direct nucleation control can effectively improve the product purity
Based on the current progress of pharmaceutical crystallization process control, this paper summarizes the important advances of industrial crystallization process control through process analysis technology and control strategy, and discusses the application of feedback control strategy for the improvement of purity, particle size, crystal shape, and crystal form in the perspective of product engineering
Summary
Crystallization is an important unit operation in major sectors of the chemical process and allied industries. Many PAT tools have been lately developed and applied for crystallization process monitoring and control through several crystallization control strategies, namely, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR) and ultravioletvisible spectroscopy (UV/Vis), particle vision and measurement (PVM), focused beam reflectance measurement (FBRM), in situ/online image analysis, and online Raman spectroscopy. ATR-UV/Vis is a molecular spectrum that generates absorption from valence electron transitions It uses the qualitative and quantitative relationship between the composition, structure of the substance, and the ultraviolet-visible light absorption spectrum to analyze nucleation, polymorphic transformation, and in situ monitoring of supersaturation changes [9,10]. Raman spectroscopy has been used to identify differences in polymorphisms, and it can perform qualitative and quantitative studies on solvent-mediated transformation, solution concentration, and the ratio of different crystal forms in solid mixtures [12]. This paper reviews the development and application of PAT technology, the feedback control method based on PAT, and its application in the crystallization process
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