Antisolvent crystallization: Model identification, experimental validation and dynamic simulation

This paper is concerned with the development, simulation and experimental validation of a detailed antisolvent crystallization model. A population balance approach is adopted to describe the dynamic change of particle size in crystallization processes under the effect of antisolvent addition. Maximum likelihood method is used to identify the nucleation and growth kinetic models using data derived from controlled experiments. The model is then validated experimentally under a new solvent feedrate profile and showed to be in good agreement. The resulting model is directly exploited to understand antisolvent crystallization behavior under varying antisolvent feeding profiles. More significantly, the model is proposed for the subsequent step of model-based optimization to readily develop optimal antisolvent feeding recipes attractive for pharmaceutical and chemicals crystallization operations.

[1]  M. Nassar,et al.  Secondary nucleation rate of sodium chloride under different stirring conditions , 1986 .

[2]  G. Witkamp,et al.  Some antisolvents for crystallisation of sodium carbonate , 1999 .

[3]  M. Ferra,et al.  Solubilities of Sodium Chloride and Potassium Chloride in Water + Ethanol Mixtures from (298 to 323) K , 2004 .

[4]  Alan Jones,et al.  Crystallization and agglomeration kinetics during the batch drowning-out precipitation of potash alum with aqueous acetone , 1991 .

[5]  Ali Abbas,et al.  Multiscale modeling, simulation and validation of batch cooling crystallization , 2007 .

[6]  Effect of Supersaturation on Crystal Size and Number of Crystals Produced in Antisolvent Crystallization , 2002 .

[7]  M. Kitamura,et al.  Anti-solvent crystallization and transformation of thiazole-derivative polymorphs—I: effect of addition rate and initial concentrations , 2003 .

[9]  Åke C. Rasmuson,et al.  Crystallization of paracetamol in acetone–water mixtures , 1999 .

[10]  J. W. Mullin,et al.  Programmed cooling of batch crystallizers , 1971 .

[11]  Dependence of Polymorphic Transformation on Anti-Solvent Composition and Crystallization Behavior of Thiazole-Derivative Pharmaceutical , 2002 .

[12]  Å. Rasmuson,et al.  Size and morphology of benzoic acid crystals produced by drowning-out crystallisation , 1999 .

[13]  Pseudopolymorphic Crystallization of l-Ornithine-l-Aspartate by Drowning Out , 2003 .

[14]  H. Galleguillos,et al.  Compositions, Densities, and Refractive Indices of Potassium Chloride + Ethanol + Water and Sodium Chloride + Ethanol + Water Solutions at (298.15 and 313.15) K , 2003 .

[15]  H. Takiyama,et al.  Morphology of NaCl Crystals in Drowning-Out Precipitation Operation , 1998 .

[16]  Yasuaki Yabuki,et al.  Constant Supersaturation Control of Antisolvent-Addition Batch Crystallization , 2006 .

[17]  J. Asenjo,et al.  Drowning-out crystallisation of sodium sulphate using aqueous two-phase systems. , 2000, Journal of chromatography. B, Biomedical sciences and applications.

[18]  Noriaki Kubota,et al.  Production of sodium chloride crystals of uni-modal size distribution by batch dilution crystallization , 2002 .

[19]  Geert-Jan Witkamp,et al.  The growth of sodium nitrate from mixtures of water and isopropoxyethanol , 1999 .

[20]  Ali Abbas,et al.  Model-Based Optimal Strategies for Controlling Particle Size in Antisolvent Crystallization Operations , 2008 .

[21]  Crystallization kinetics of calcium nitrate tetrahydrate from MSMPR crystallizer , 1985 .

[22]  J. Vera,et al.  Liquid-Liquid Equilibrium of Aqueous Mixtures of Poly(ethylene glycol) with Na2SO4 or NaCl , 1994 .

[23]  H. Offermann,et al.  Kinetic modelling of batch precipitation reactions , 1996 .

[24]  Alan Jones,et al.  Potassium sulfate water-alcohols systems: composition and density of saturated solutions , 1990 .

[25]  Reginald B. H. Tan,et al.  Seeding and constant-supersaturation control by ATR-FTIR in anti-solvent crystallization , 2006 .

[26]  Salting-out precipitation of cocarboxylase hydrochloride from aqueous solution by addition of acetone , 1986 .

[27]  Ali Abbas,et al.  Optimization in seeded cooling crystallization: A parameter estimation and dynamic optimization study , 2007 .

[28]  J. Rawlings,et al.  Model identification and control of solution crystallization processes: a review , 1993 .

[29]  Geert-Jan Witkamp,et al.  Antisolvent crystallization of anhydrous sodium carbonate at atmospherical conditions , 2001 .

[30]  S. Katz,et al.  Some problems in particle technology: A statistical mechanical formulation , 1964 .

[31]  John S. J. Hsu,et al.  Bayesian Methods: An Analysis for Statisticians and Interdisciplinary Researchers , 1999 .

[32]  J. W. Mullin,et al.  Programmed cooling crystallization of potassium sulphate solutions , 1974 .

[33]  James V. Beck,et al.  Parameter Estimation in Engineering and Science , 1977 .

[34]  Pui Shan Chow,et al.  Effects of operating conditions on agglomeration and habit of paracetamol crystals in anti-solvent crystallization , 2005 .

[35]  Alan Jones,et al.  Growth and dissolution kinetics of potassium sulphate crystals in aqueous 2-propanol solutions , 1989 .

[36]  O. Linnikov.  Part 1: Kinetics and mechanism of the crystallization process , 2006 .

[37]  T. Brubaker,et al.  Nonlinear Parameter Estimation , 1979 .

[38]  R. Braatz,et al.  Direct design of pharmaceutical antisolvent crystallization through concentration control , 2006 .

[39]  M. Mazzotti,et al.  Modeling the Gas Antisolvent Recrystallization Process , 2002 .

[40]  J. Tóth,et al.  The formation of fine particles by salting-out precipitation , 2005 .