Influence of Controlled Fluid Shear on Nucleation Rates in Glycine Aqueous Solutions

Forsyth, Carol; Mulheran, Paul A.; Forsyth, Claire; Haw, Mark; Burns, Iain S.; Šefčı́k, Ján

doi:10.1021/cg5008878

Cited by 69 publications

(101 citation statements)

References 42 publications

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“…The induction time for the rotor-stator mixer also decreased with increasing calorimetric power until a threshold was reached; thereafter, the induction time did not reduce significantly anymore. These results are also in agreement with observations for both gassing and shear-induced nucleation, likely attributing the reduced induction times to one of these effects [3,24,25].…”

Section: Induction-time Measurementssupporting

confidence: 90%

“…This was already mentioned in the literature for ultrasound, and shearand gas-induced nucleation, but was not yet shown for rotor-stator mixers [3,24,25,33]. However, the mechanism via which both techniques induce nucleation during these experiments is hypothesized to be different, as there was a completely different influence of supersaturation.…”

Section: Induction-time Measurementsmentioning

confidence: 67%

“…The crystallization process determines the final crystal properties such as particle size distribution (PSD), purity, shape, and polymorphic form, which greatly influence downstream processing and bioavailability [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Reducing the Induction Time Using Ultrasound and High-Shear Mixing in a Continuous Crystallization Process

et al. 2018

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Continuous crystallization in tubular crystallizers is of particular interest to the pharmaceutical industry to accurately control average particle size, particle size distribution, and (polymorphic) shape. However, these types of crystallizers require fast nucleation, and thus, short induction times at the beginning of the flow process, which is challenging for larger and complex organic molecules. High shear and/or the presence of bubbles were identified to influence the nucleation behavior. This work investigates the effects of both high-shear mixing and ultrasound on the anti-solvent crystallization of paracetamol in acetone-water. Both devices generate intense amounts of shear and gas bubbles. Generally, the results show that increasing input power decreases the induction time significantly for both the rotor-stator mixer and ultrasound probe. However, the induction time is almost independent of the supersaturation for the ultrasound probe, while the induction time significantly increases with decreasing supersaturation for the rotor-stator mixer. In contrast, the particle size distribution for the rotor-stator mixer is independent of the supersaturation, while increasing supersaturation decreases the particle size for the ultrasound probe.

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Section: Induction-time Measurementssupporting

confidence: 90%

Section: Induction-time Measurementsmentioning

confidence: 67%

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Reducing the Induction Time Using Ultrasound and High-Shear Mixing in a Continuous Crystallization Process

et al. 2018

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“…4 When the induction time was reached, solutions became turbid over a relatively short time scale (as short as around 10 s), leading to a sharp decrease in transmission and an increase in mean pixel intensity. Induction times were obtained by finding the point of inflection of the rising (or falling) signals.…”

Section: Crystal Growth and Designmentioning

confidence: 99%

Scaling of Glycine Nucleation Kinetics with Shear Rate and Glass–Liquid Interfacial Area

Forsyth

Burns

Mulheran

et al. 2015

Crystal Growth & Design

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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. ...

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“…Besides, both theoretical and experimental evidences point out that shear rates have an influence on the nucleation behavior [23]. Tests performed in Couette flow conditions by Forsyth and coworkers show an increased nucleation rate as a function of average shear rate inside a tubular reactor [24]. We demonstrated recently that the application of specific flow structures by using capillary tubing and high flow velocities result in high nucleation rates while a solution is cooled down to the supersaturated state [21].…”

Section: Introductionmentioning

confidence: 92%

The creation and testing of a fully continuous tubular crystallization device suited for incorporation into flow chemistry setups

et al. 2019

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The study presents the use of a continuous crystallization device that can be directly incorporated into flow chemistry setups. Inside this device spontaneous nucleation and growth of organic molecules are controlled and maintained, using Aspirin as model molecule. The identification of the optimal crystallization scenario is discussed in view of the chemical stability of Aspirin and based on the determination of the solubility and the metastable zone width corresponding to the presented experimental setups. Physicochemical analyses combined with heat transfer modeling of the solution whilst flowing through a capillary placed inside a thermostated water bath provide the desired cooling profile and hence the degree of supersaturation along the system. The crystalline quality and stability of the crystalline output is evidenced for two different pump setups having distinguished flow patterns to show the independence on the flow stability, an important parameter for the success rate of the complete reaction scheme and in the perspective of operation scale-up. Reproducible output of material with narrow size distributions is obtained throughout all experiments.

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Influence of Controlled Fluid Shear on Nucleation Rates in Glycine Aqueous Solutions

Abstract: 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

Cited by 69 publications

References 42 publications

Reducing the Induction Time Using Ultrasound and High-Shear Mixing in a Continuous Crystallization Process

Reducing the Induction Time Using Ultrasound and High-Shear Mixing in a Continuous Crystallization Process

Scaling of Glycine Nucleation Kinetics with Shear Rate and Glass–Liquid Interfacial Area

The creation and testing of a fully continuous tubular crystallization device suited for incorporation into flow chemistry setups

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