In Situ Measurement of Solution Concentration during the Batch Cooling Crystallization of l -Glutamic Acid using ATR-FTIR Spectroscopy Coupled with Chemometrics (original) (raw)
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Chemical Engineering & Technology, 2010
The feedback control policy of the reactive crystallization process is studied. A concentration of a crystallizing compound is used to compute the feedback in the closed-loop control of semi-batch precipitation. The pH is used as a second feedback value, and the dynamic change of the set value is based on the mass of added acid. The concentration of L-glutamic acid is determined from measured MID-IR attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra based on a multivariate model. The importance of the supersaturation level control at the nucleation moment and the effect of different supersaturation levels on the quality of the product crystals are studied by using a 50-L crystallizer. The studied crystal properties of the product are polymorphism (reported metastable aand stable b-forms) and crystal size. The results show that the feedback process control system developed in this study makes it possible to control the formation of polymorphs effectively.
Kinetics of (R,S)- and (R)-mandelic acid in an unseeded cooling batch crystallizer
Journal of Crystal Growth, 2010
The objective of this work is to determine the nucleation and growth kinetics of (R,S)-mandelic acid ((R,S)-MA) and (R)-mandelic acid ((R)-MA) in aqueous solutions using an unseeded cooling crystallization process. To obtain the nucleation and growth kinetics, the solubility, metastable zone limits, and supersaturation were measured by in-situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and focused beam reflectance measurement (FBRM). The nucleation rate and growth rate parameters were determined by a nonlinear optimization algorithm. The effects of initial concentration and cooling rate on supersaturation and the nucleation rate are also discussed. & 2010 Elsevier B.V. All rights reserved. 'cloud points', points on the falling temperature profile at which crystal nucleation is first observable. In contrast to the saturation limit (solubility), the metastable limit is not thermodynamically defined and strongly depends on process parameters such as cooling rate, agitation, and impurities [11]. Although several prediction methods [12-14] have been introduced, the obtainment of accurate solubility curve and metastable limits has to rely on experimental measurement [15,16]. Reliable online measurement of solution concentration is a prerequisite for the control of supersaturation in crystallization processes. Several methods and devices can be considered for the online measurement of supersaturation. Solute concentration can usually be determined by the measurements of density [17], conductivity [18], refractive index [19], and infrared spectra [15] of the solution. Results indicate that ATR-FTIR spectroscopy offers the most accurate measurement of solute concentrations, particularly in organic systems [20,21].
Industrial & Engineering Chemistry Research, 2004
The effects of reactor internals and reactant mixing on the measured metastable zone width (MSZW) associated with the batch crystallization of L-glutamic acid from supersaturated aqueous solutions are presented. The results of cooling crystallization experiments, as carried out at three reactor scales (450 mL, 2 L, and 20 L) agitated at various stirring speeds using an industrystandard retreat curve impeller with a single beaver-tail baffle, are shown. The observed MSZWs are mostly found to decrease with increasing stirring speed, with enhanced nucleation also being observed as the reactor scale increased; albeit hindered nucleation was found at higher stirrer speeds in the 450-mL reactor experiments. The MSZW data are correlated with Reynolds number to reveal a model reflecting the combined influences of hydrodynamics and scale on the overall nucleation process.
Journal of Crystal Growth, 2009
Batch-reactive crystallization of the two polymorphs of L-glutamic acid was studied using in-line Raman and ATR FTIR spectroscopy. It was observed that the barrier to the nucleation of the stable b-form was higher, and thus the occurrence of b-form nucleation requires a higher supersaturation level. The local supersaturation level inside the reactive crystallizer is significantly affected by the feeding manner of the reactant. When the reactant was fed to a poorly mixed zone, such as the surface of the liquid, a high local supersaturation level was generated near the feeding point. This high local supersaturation level drastically increased with the increase in the concentrations of the reactants. As a consequence, the fraction of the b-form increased with the increase in reactants concentrations. On the other hand, feeding the reactant to a well-mixed zone near the impeller can avoid the occurrence of high local supersaturation, and therefore the dependence of the polymorphic composition of the final product on the concentration of the reactants can be reduced. The information obtained from the spectroscopy leads to improved understanding of the precipitation process and offers great potential for process optimization and control of crystalline quality.
Chemical Engineering Science, 2001
Recently, fourier transform infraRed (FTIR) spectroscopy was reported as a promising technique for in situ measurement of supersaturation during solution crystallization processes. The attenuated total re#ection (ATR) probes appeared to be particularly suited to the chemical and physical complexity of industrial suspensions. However, to be used in an industrial context, the technique must be easily and quickly adaptable to di!erent systems. In order to achieve such an aim, a calibration procedure to monitor supersaturation from FTIR measurements is presented. General comments and recommendations about important technical aspects of the technique are also given. Then the technique is used to develop e$cient procedures for the determination of solubility and metastability curves. The crystallization of three "ne chemical products is studied, thanks to on-line FTIR measurements of supersaturation and o!-line CSD determinations. It is shown that the monitoring of supersaturation is a valuable tool for an improved analysis of key phenomena involved during crystallization processes (primary and secondary nucleation, agglomeration, phase transition, seeding, etc.).
HAL (Le Centre pour la Communication Scientifique Directe), 2020
In this work, the fractionation of water-ethanol mixtures by supercritical carbon dioxide at 333 K and 10.1 MPa was used as a model system to compare experimental extract and raffinate compositions and overhead loadings at laboratory, pilot and industrial scales to contribute toward a sizing methodology for counter-current supercritical fractionation columns. A series of three columns with an internal diameter of 19, 58 and 126 mm and with a height of 2, 4 and 8 m respectively were used for the different scales, meaning scaling factors from 9 to 44 between consecutive columns. The massic solvent-to-feed ratio was varied between 5.2 and 78.8. Experimental results at the different scales are analyzed and compared from the thermodynamic, mass transfer and column hydrodynamics points of view; and also using process simulation by equilibrium-stage models. In total, 42 successful experimental runs are taken into account, including 6 at a pilot scale unit and 2 at an industrial scale.
Organic Process Research & Development, 2002
In the pharmaceutical industry, a vast number of compounds are produced by solution crystallization, making the design and development of such processes of critical importance. The kinetics of crystal growth and nucleation, the fundamental mechanisms of a solution crystallization process, are strongly dependent on supersaturation (the difference between solution concentration and the saturation concentration). The present study uses attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy, coupled with robust chemometric techniques, for the on-line measurement of solution concentration of two pharmaceutical compounds in multicomponent systems in the presence of impurities and over a wide range of temperature. To our best knowledge, this is the first time that ATR FTIR spectroscopy has been applied to a multicomponent pharmaceutical system. The resulting models show high accuracy in predicting the solution concentration and are applied successfully in measuring the solubility for the cases of cooling and antisolvent crystallization.