(116b) Oiling out During Crystallization Processes: Experimental Investigation and Modeling

Oiling out is an often unwanted effect during cooling crystallization processes. Prior to nucleation of the first crystals the solution becomes cloudy caused by the formation of a second liquid phase (oiling out). Thus from a thermodynamic point of view, this phenomenon is supposed to be caused by a superposition of (metastable) liquid liquid demixing and solid liquid phase equilibrium (solubility). Depending on the position of the liquid-liquid miscibility gap, different crystallization conditions can be obtained. Consequently, this behavior disturbs the crystallization process and in most cases affects the product properties like crystal size and form, affinity of agglomeration and hence the product purity [1]. Therefore, the knowledge of such liquid-liquid phase equilibria in addition to solubility and supersaturation data is essential for designing industrial crystallization processes.

Oiling out has initially been observed during cooling crystallization of complex molecules like pharmaceuticals, proteins or polymers from solutions [2-5]. Hence, this work investigates the influence of solute as well as solvent properties on the oiling out behavior. Therefore, the required solubility data were measured gravimetrically as well as by using differential scanning calorimetry. The crystallization and oiling out temperatures were obtained in batch crystallization experiments, when either the first visually observable crystals were detected or the solution became cloudy during cooling.

Investigating the crystallization of the model substance polyethylenglycoldimethylether (pegdme) for different molecular weights from pure solvents proved the dependence of oiling out on the molecular size of the solute without chemical modification of the solid. An oiling out was detected during the cooling process of pegdme with a molar mass of 2000 g/mol, whereas no oiling out was observed for the crystallization of pegdme with less molar mass from all solvents used. Furthermore, the influence of the solvent on the oiling out was investigated by the crystallization of pegdme (M=2000 g/mol) from solvents of different solvent classes. The size and position of the oiling-out region varies for the crystallization of pegdme from the solvents used. Thus, changing the solvent can lead to avoid an unwanted oiling out. This effect was also proven for the crystallization of 4,4' dihydroxydiphenylsulfone (DHDPS) from solvent mixtures. An oiling out occurred during the cooling process of DHDPS from water/acetone mixtures, whereas no oiling out was detected during the crystallization of DHDPS from water/2-propanol solutions [1]. Additionally, for designing industrial crystallization process units, modeling and prediction of oiling out is important to reduce this experimental effort. Applying the PC-SAFT equation of state, this work demonstrates the feasibility of predicting the oiling-out behavior for the mentioned systems based on binary solubility data only.

[1] K. Kiesow, et al., "Experimental investigation and prediction of oiling out during crystallization process," Journal of Crystal Growth, vol. 310, pp. 4163-4168, Aug 15 2008. [2] J. A. Thomson, et al., "Binary-Liquid Phase-Separation and Critical Phenomena in a Protein Water Solution," Proceedings of the National Academy of Sciences of the United States of America, vol. 84, pp. 7079-7083, Oct 1987. [3] M. Muschol and F. Rosenberger, "Liquid-liquid phase separation in supersaturated lysozyme solutions and associated precipitate formation/crystallization," Journal of Chemical Physics, vol. 107, pp. 1953-1962, Aug 8 1997. [4] O. Galkin and P. G. Vekilov, "Control of protein crystal nucleation around the metastable liquid-liquid phase boundary," Proceedings of the National Academy of Sciences of the United States of America, vol. 97, pp. 6277-6281, Jun 6 2000. [5] D. Vivares and F. Bonnete, "Liquid-liquid phase separations in urate oxidase/PEG mixtures: Characterization and implications for protein crystallization," Journal of Physical Chemistry B, vol. 108, pp. 6498-6507, May 20 2004.