The nucleation of glycine was investigated in supersaturated aqueous solutions exposed to well-controlled fluid shear under isothermal conditions. Shear rates between 25s-1 and 1000s-1 were studied using Couette and capillary flow devices. Induction times were obtained from

We demonstrate that nanofiltration of aqueous glycine solutions has a pronounced effect on laser-induced nucleation. Two nucleation regimes were observed in non-filtered, irradiated solutions under isothermal conditions: a rapid initial regime associated with laser induced nucleation, and a second much slower spontaneous nucleation regime. Filtration of the solutions prior to irradiation greatly suppressed the rapid regime, while the slow regime was similar regardless of filtration or irradiation, for all supersaturations studied. A clear effect of filtration on crystal polymorphism was also observed. Non-filtered irradiated solutions at a lower supersaturation almost exclusively yielded the -polymorph, while at higher supersaturations there was significant presence (~40%) of the -polymorph. On the other hand, filtered solutions

The influence of experimental conditions on polymorphic outcome and transformations during cooling crystallization of carbamazepine (CBZ) from anhydrous ethanol has been investigated. Stirring was found to be the most important controlling factor for the initial polymorphic outcome in solutions prepared using commercial CBZ powder. For quiescent conditions, a few large crystals of the metastable trigonal α form (II) initially appeared, undergoing subsequent slow transformation into the stable P-monoclinic β form (III). Under sufficiently vigorous stirring, the induction times observed were clearly defined by the onset of turbidity, which was due to formation of a large number of small form III prismatic crystals. In experiments with solutions prepared by using recrystallized CBZ, significantly shorter induction times were observed under stirring conditions: a large number of small form II needleshaped crystals initially formed at the onset of turbidity and then relatively rapidly transformed to small crystals of form III. This indicates a possible effect of impurities in the commercial CBZ powder inhibiting rapid nucleation of form II under stirring conditions. In situ monitoring of CBZ polymorphic outcome was performed using custom-built experimental setup for simultaneous measurement of intensity of transmitted and scattered light. Distinct pathways in two-variable intensity plots were observed for formation of each respective polymorph under stirring conditions. The same monitoring technique should be readily applicable to other systems.

No abstract

The scaling of the nucleation kinetics of glycine was investigated in supersaturated aqueous solutions under isothermal conditions. Induction times were measured in a Couette cell with a wide range of average shear rates γ̇a vg (25−250 s −1 ) and a range of glass−liquid interfacial areas A (2.5−10 cm 2 per mL solution). The probability distributions of induction times were found to scale with shear rate and glass−liquid interfacial area, with the characteristic time scale (γ̇a vg A) −1 . Primary nucleation rates and growth times to reach detection (estimated from the probability distributions) were both dependent on this time scale. In-situ dynamic light scattering revealed mesoscale clusters in the solutions that increased in size over time at rates which also depended on this time scale. The increase in size was thought to be due to the shear-enhanced aggregation or coalescence of mesoscale clusters leading to a higher number of larger mesoscale clusters, resulting in higher rates of primary nucleation. ■ INTRODUCTIONFluid shear has been reported to influence the nucleation of crystals from solution. It is well-known to have an effect on secondary nucleation since shear forces imposed on a crystal face can be sufficient to produce secondary nuclei from the crystal surface, 1,2 but the effect that fluid shear can have on primary nucleation from solution is not well understood to date, particularly for small organic molecules. 3,4 Studies have reported that fluid shear can influence the primary nucleation of various organic compounds from solution, including protein molecules such as lysozyme 5−7 and insulin 8 and smaller molecules such as glycine 4,9 carbamazepine, 10 butyl paraben, 3 and m-hydroxybenzoic acid. 11 In some cases, fluid shear can enhance primary nucleation rates, 3,4,9−11 while in others, it can suppress them, 3,5−7 and the mechanisms behind the role of fluid shear on primary nucleation therefore remain unclear.In many studies on the influence of fluid shear on nucleation, the shear rates were not well quantified so in our previous work, 4 Couette and capillary flow devices were used to achieve controlled, quantifiable flow conditions. It was shown that this controlled fluid shear could be used to significantly enhance primary nucleation rates in supersaturated glycine solutions. 4 Controlled fluid shear in a Couette cell has been found to enhance primary nucleation in other systems, including butyl paraben 3 and m-hydroxybenzoic acid. 11 While it is recognized that complex flow fields are present in industrial crystallization processes, it is useful to understand the effect of simple, wellcontrolled flow fields on various aspects of the crystallization process, such as primary nucleation, and then map this information on more complex equipment through knowledge of shear rate distributions obtained for example by computational fluid dynamics.In addition to fluid shear, exposure of solutions to a solid surface such as the walls of the glass Couette cell is known to have an influence on nucleation. ...