(702f) Sonocrystallization of L-Asparagine Monohydrate: Modeling and Optimization.

Producing crystals with target attributes consistently is a great challenge in any crystallization process due to stochastic nature of the nucleation event and the limited number of manipulated variables. The use of power ultrasound (defined as frequencies from 20 to 100 kHz) provides an interesting approach to induce nucleation at low supersaturation in a controlled way [1]. Several studies have demonstrated the benefits of applying ultrasound during a cooling or anti-solvent crystallization process such as faster and uniform primary nucleation, higher yield, reduced agglomeration, narrow crystal size distribution, control of polymorphism, and generation of internal seed [2]-[3].

 The development of an effective mathematical model describing the crystallization dynamics is a crucial issue towards finding the optimal process performance and to control the crystal product properties. Here we develop and validate a mathematical model based on population balance framework for the ultrasound-assisted unseeded batch cooling crystallization of L-asparagine monohydrate, an important amino acid, from its aqueous solution. The population balance model considers the relevant fundamental events of the crystallization process, such as nucleation, growth, and breakage phenomena. An additional kinetic expression is introduced for induced nucleation due to ultrasound irradiation [4]. Application of ultrasound induces energy into the system and this in turn leads to temperature rise. The modeling considers this rise in temperature appropriately. The population balance model coupled with mass balances is solved by high resolution finite volume discretization with a flux limiter. 

A series of ultrasound-assisted batch cooling crystallization experiments have been conducted systematically and the solute concentration data measured by high performance liquid chromatography and final mean crystal size measured by laser diffraction are used to simultaneously extract all kinetic parameters using the population balance model and a nonlinear optimization technique. The model has been fully validated with new experimental data and the good agreement between model predictions and experimental observations clearly demonstrates the predictive ability of the model. Experimental data and model simulations show that the ultrasound significantly reduces the metastable zone width for L-asparagine monohydrate, enhances the nucleation rate, and induces early nucleation. The developed model is then used to solve a set of dynamic optimization problems related to particle engineering. The model is also used to determine the region of attainable size for such a sonocrystallization process.

References:

[1] G. Ruecroft, D. Hipkiss, T. Ly, N. Maxted, and P. W. Cains, Org. Proc. Res. Dev. 9, 923-932, 2005.

 [2] O. Narducci and A. G. Jones, Cryst. Growth Des. 12, 1727â??1735, 2012.

 [3] M. Kurotani and I. Hirasawa, Chem. Eng. Res. Des. 88, 1272â??1278, 2010.

 [4] A. Kordyllaa, T. Krawczyka, F. Tumakakab and G. Schembecker, Chem. Eng. Sci. 64, 1635â??1642, 2009.