Abstract
The influence of shear rate on the primary nucleation of para-amino benzoic acid in water has been investigated via a series of cooling crystallization experiments. For each experiment, we recorded the induction time at various temperatures and supersaturation ratios, employing two flow devices: a capillary tube in which the solution was divided into hundreds of monodisperse droplets and a set of stirred vials. The capillary tube was used to perform experiments in stagnant conditions (motionless droplets) and low shear rate conditions (flowing droplets), while the stirred vials were used to perform experiments at relatively high shear rates. In this way, a wide range of shear rates was investigated. Comparing the results obtained for the motionless and flowing droplets, we saw that the nucleation rate is significantly increased (by several orders of magnitude) by the shear field; however, when the shear rate increases beyond a certain level (stirred vials experiments), we observed a drop in the nucleation rate. Thus, the results demonstrate a non-monotonic dependence of primary nucleation rate on shear rate. Various mechanisms to explain the effect of shear on nucleation are quantitatively and qualitatively discussed; however, at present no definitive conclusion can be drawn to identify the controlling mechanism.
Highlights
Cooling crystallization is extensively used by the pharmaceutical industry to produce and purify Active Pharmaceutical Ingredients (APIs)
Evidence that mechanical perturbations in supersaturated solutions can trigger nucleation can be found from the beginning of the 20th century; systematic studies of the effect of fluid dynamics on nucleation kinetics only started in the 60s, when Mullin and Raven (1962) measured the metastable zone width (MZW) of a number of aqueous salt solutions as a function of the speed of the stirrer used to agitate them
We estimated the primary nucleation kinetics of para aminobenzoic acid in water in different fluid dynamic conditions using two different experimental devices: a capillary tube where the crystallising solution was held in form of droplets and a set of stirred vials
Summary
Cooling crystallization is extensively used by the pharmaceutical industry to produce and purify Active Pharmaceutical Ingredients (APIs). Evidence that mechanical perturbations in supersaturated solutions can trigger nucleation can be found from the beginning of the 20th century; systematic studies of the effect of fluid dynamics on nucleation kinetics only started in the 60s, when Mullin and Raven (1962) measured the metastable zone width (MZW) of a number of aqueous salt solutions as a function of the speed of the stirrer used to agitate them. Their results show that the MZW decreases as the agitation rate increases, reaches a minimum and increases again. Liu and Rasmuson (2013) and Liu et al (2014, 2015) per-
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