(472f) The Influence of Solution Conditions on the Self-Assembly of Pre-Nucleation Clusters
AIChE Annual Meeting
2017
2017 Annual Meeting
Separations Division
Crystallization of Pharmaceutical and Biological Molecules
Wednesday, November 1, 2017 - 9:45am to 10:05am
Using the models proposed in more recent works is being shown that bigger pre-nucleation clusters provides an environment giving more chances of survival to the nucleus inside it. These findings were tested experimentally using a number of industrially relevant molecules (arginine, glycine, glutamic acid). These molecules are particularly attractive as they have relatively large nucleation times. In addition the formation of pre-nucleation clusters as nucleation precursors for them has been reported in literature. Using DLS it was shown that in aqueous systems, the size of the pre-nucleation clusters scales with the supersaturation. These findings are in accordance with the findings proposed from previous works. Upon filtration, both in a supersaturated and an undersaturated regime, the pre-nucleation clusters recover their initial size in a few hours, in the absence of any agitation.
Experiments were conducted in systems containing water and ethanol to investigate the influence of solutionâs chemical potential on the size of the pre-nucleation clusters. It is shown that, in both the undersaturated and the supersaturated regime, the formation of the pre-nucleation clusters follows the fundamentals of self-assembly in solution.4 The findings suggest that the influence of the solvent can overcome that of supersaturation, for example an aqueous system containing arginine at Sâ0.5 (0.8 g of L-Arginine) gives bigger pre-nucleation clusters than a solution containing 30 % v/v ethanol at Sâ0.9.
The findings of this work verify the majority of the findings reported in literature. However, it reports different kinetics of recovery of the pre-nucleation clusters size upon filtration. It highlights the applicability of the fundamentals of self-assembly in solution. The findings suggest that in depth understanding of the self-assembly phenomena are required for the development of efficient strategies for the control of crystallization kinetics via stirring5 and for the formulation of amorphous solid dispersions.
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