Crystallization in continuous flow conditions is a well-known process for heavy weight molecues like polymers, where shear stresses are used to increase nucleation rates and finetune the end-product. More and more studies point out that also the crystallization of low molecular weight molecules in solution is affected by flow effects like shear rate, mechanical restraints, and turbulence. A new cooling crystallization method uses narrow cappilary tubings to increase shear rates inside the crystallizing liquid at high liquid velocities. Sudden shrinkages and expansions - flow restrictions - placed in series in the flow path prior of the cooling phase have the power to increase the nucleation rate further downstream with at least one order of magnitude, at invariant crystallization conditions.<br/>Current study represents the hydrodynamic investigation of the behavior of the liquid when placing such restrictions in the flowpath. They impact cooling and create flow instabilities such as vortex shedding and shear rate waves further downstream the cappilaries; at the point where crystal nucleation takes place. The combination of numerical simulations of flow patterns inside narrow tubings containing sudden shrinkages and expansions and experimental crystallization data render new considerations and insights in the way small molecules can nucleate at very high rates while flowing inside capillary tubings. This information will impact the way industrial production of crystals of e.g. active pharmaceutical ingredients is performed since costfull process steps such as seed preparation and post-process grinding and milling can become obsolete - since crystal growth can be arrested at any time using proposed methodology via continuous filtration.

Impact of flow turbulence in narrow capillaries on the nucleation rate of small organic molecules

2019 Spring National Meeting

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