A monitoring policy to improve the mastery of the crystal size distribution during batch solution crystallization (original) (raw)
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An Online Strategy To Increase the Average Crystal Size during Organic Batch Cooling Crystallization
In situ attenuated total reflectance Fourier transform infrared (FTIR) measurements were shown to allow the online monitoring of supersaturation during solution crystallization processes, thus opening up new monitoring and control possibilities. With this aim in view, the monitoring of unseeded batch cooling solution crystallizations of two agrochemical products was investigated. The FTIR measurements of solute concentrations were used to develop a fines dissolution technique, based on a controlled heating-up procedure after primary nucleation. The strategy only requires the knowledge of the solubility curve and was deliberately designed to be robust and easy to implement. Two organic solute/solvent systems were studied. It is clearly demonstrated that the technique allows one to improve both the reproducibility of the final crystal size distribution and the mean crystal size. For Isoproturon, a well-known pesticide, the average final size is increased up to 90%. The efficiency of the monitoring procedure is also shown to depend on the solute/solvent system in question.
Real-time evaluation of the concentration of impurities during organic solution crystallization
Powder Technology, 2003
ATR FTIR spectroscopy was previously presented as a promising technique for measuring supersaturation on-line during crystallization operations, without requiring complex hardware developments. The present paper reports new experimental results where, in addition to the determination of the concentration of the main dissolved product, the real-time measurement of the concentration of impurities is shown to be feasible before the onset of primary nucleation. Using spectral data obtained with both clear solutions and suspensions, the calibration of the in situ infrared sensor was performed to relate the time variations of the concentrations of the main product and of its main impurity, in the presence of both pH and temperature variations. As far as the on-line monitoring of crystallizing slurries is concerned, it is shown that measuring the concentration of impurities is very difficult to perform. However, the quantitative evaluation of impurities present in the clear solution feeding the crystallizer is valuable and expected to allow further design of monitoring and control policies leading to the reduction of batch-to-batch variations of the final quality of the solid produced. D
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.).
Supersaturation tracking for the development, optimization and control of crystallization processes
Chemical Engineering Research & Design, 2010
Supersaturation is the key driving force in crystallization operations, determining nucleation and growth kinetics, and heavily influencing physical mechanisms such as agglomeration. Therefore, knowledge of the bulk supersaturation during crystallization can greatly enhance process understanding and optimization.In this paper, a method which facilitates the calibration-free use of in situ ATR-FTIR for crystallization development and control is presented. This methodology uses solute-specific ATR-FTIR absorption peak heights to describe solute solubility and dissolved concentration and, in turn, supersaturation, for the optimization of cooling crystallizations of an active pharmaceutical ingredient (API) and benzoic acid. The approach presented facilitates rapid process understanding, design and optimization. Specifically, the potential to significantly reduce cycle time for both systems studies is demonstrated. In addition, the potential of the method to form the basis of a process ...
International Journal of Chemical Reactor Engineering, 2008
The batch cooling crystallization of an industrial active pharmaceutical ingredient that exhibits a needle-like habit was investigated. A model of the time variations of key physical properties of particles (crystal size distribution CSD and specific area) was designed using an approach based on the simple population balance equation. The experiments were monitored thanks to three in-situ process analytical sensors (Mid-IR spectroscopy, in-situ microscopy and laser backscattering). Primary and secondary surface nucleation mechanisms as well as growth of the main crystal dimension (length) were described resulting in a six parameter model. The model roughly represents the effects of different cooling strategies on the supersaturation profile, the CSD and the specific area of the final particles. First, a very weak primary nucleation occurs leading to an initial population of a few large crystals. A second population of crystals is generated afterwards through secondary nucleation mec...
On Line Monitoring of Batch Pharmaceutical Crystallization Using Atr Ftir Spectroscopy
IFAC Proceedings Volumes, 2002
Chemists and engineers involved in the production of solid drugs have to deal with difficult new challenges, including the on-line mastery of the crystal habits and size distribution or the control of polymorphic transitions. A major limitation to improving the control of industrial crystallizers lies in the lack of versatile and reliable on-line sensors. Supersaturation measurements can be performed using in situ Mid-Infrared spectroscopy. New potential applications of the technique are described : the acquisition of key data characterising the solute/solvent system in question, the design of improved monitoring and/or operating strategies, and the monitoring of polymorphic transitions during crystallization operations.
INDUSTRIAL CRYSTALLIZATION AND PRECIPITATION FROM SOLUTIONS: STATE OF THE TECHNIQUE
Brazilian Journal of Chemical Engineering, 2001
Crystallization and precipitation from solutions are responsible for 70% of all solid materials produced by the chemical industry. Competing with distillation as a separation and purification technique, their use is widespread. They operate at low temperatures with low energy consumption and yield with high purifications in one single step. Operational conditions largely determine product quality in terms of purity, filterability, flowability and reactivity. Producing a material with the desired quality often requires a sound knowledge of the elementary steps involved in the process: creation of supersaturation, nucleation, crystal growth, aggregation and other secondary processes. Mathematical models coupling these elementary processes to all particles in a crystallizer have been developed to design and optimize crystallizer operation. For precipitation, the spatial distribution of reactants and particles in the reactor is important; thus the tools of computational fluid dynamics are becoming increasingly important. For crystallization of organic chemicals, where incorporation of impurities and crystal shape are critical, molecular modeling has recently appeared as a useful tool.
A new policy for the estimation of the course of supersaturation in batch crystallization
The Canadian Journal of Chemical Engineering, 1996
A continuing effort is being made in the development of on-line sensors for the monitoring and control of crystallization processes. Applied on-line calorimetry provides an estimate of the instantaneous heat release due to crystallization advancement. Two approaches to the implementation of such "soft sensors" are described and difficulties arising in the case of on-line multipurpose non-isothermal applications are outlined. Off-line estimates of concentration and supersaturation profiles during typical batch evaporative crystallizations are reported. Particular attention is paid to the detection of second, late nucleation bursts occurring in cases of poor crystal growth and rapid temperature decay. Des recherches sont continuellement menees pour perfectionner les capteurs en ligne pour la surveillance et la regulation des procedes de cristallisation. La calorirnetrie en ligne appliquee foumit une estimation du degagement de chaleur instantane dii a la progression de la cristallisation. Nous decrivons deux methodes d'implantation de ces (capteurs doux)) et soulignons les diffcultes qui surviennent dans les applications non isothermes a objectifs multiples en ligne. Nous donnons des estimations hors-ligne des profils de concentration et de sursaturation durant les cristallisations avec evaporation discontinues typiques. Une attention particuliere est accordee a la detection des eclatements de nucleation tardives et secondaires qui surviennent en cas d'une faible croissance des cristaux et d'une decroissance rapide des temperatures.
Determination of Operating Conditions for Controlled Batch Cooling Crystallization
Chemical Engineering & Technology, 2006
ABSTRACT In batch cooling crystallization, the supersaturation courses, obtained at different operating conditions, directly influence the crystallization kinetics. Therefore, the product sizes obtained strongly depend on the operating conditions. In order to control the supersaturation level during batch processes, a cooling model was introduced which included the seeding conditions, cooling rate, batch time, and crystallization kinetics. The cooling profiles, which maintain the different constant levels of supersaturation, were, therefore, predicted by numerically solving the model equation. Furthermore, the mean product sizes, obtained with the different specified cooling profiles, were simulated using the mass balance and the moment transformation of the population balance. Based on the simulation results, the relationship between the operating conditions, the supersaturation level, and product size was established. Hence, a strategy to select the appropriate operating conditions, in order to meet the required mean product size, was demonstrated. The results highlight that, by using the developed strategy, the batch cooling crystallization can be operated at optimal conditions, e.g., short batch time, slow cooling rate, or low seed loading. A potassium dihydrogen phosphate (KDP) system was selected for the case study.