Design and characterization of Kenics static mixer crystallizers

Thomas, Kiran Mathew; Nyande, Baggie W.; Lakerveld, Richard

doi:10.1016/j.cherd.2022.01.025

Cited by 20 publications

(12 citation statements)

References 72 publications

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“…We can see that as the number of mixing elements increases, the dispersion in the pipe decreases. After 14 mixers, or within the first 25 cm of the reactor, the dispersion number is less than or equal to 0.04 in all cases (Figure A); this ensures that all the molecules inside the crystallizer have the same residence time, ensuring homogeneous conditions and uniformity in the final product. ,, Moreover, the crystallizer after 10 mixing elements is comparable to a series of at least 15 CSTRs (Figure B). The dispersion values obtained for the acetone–water system are higher in the initial mixing elements because the injected flow rate is 3 times higher than the one entering axially, thus causing backflowing effects.…”

Section: Resultsmentioning

confidence: 99%

“…Simulation tools developed in the framework of CFD are considered a very reliable resource for predicting the mixing length inside tubular vessels, as reported in several works in the literature. ,, To support the assumption of plug-flow behavior inside the crystallizer, a series of CFD analyses were carried out to evaluate the mixing length and the residence time distribution of a liquid stream inside the PFC. The modeled geometry consisted of a pipe with lateral injection, equipped with 14 Kenics type static mixers, with a diameter of 1.2 cm and a length of 32.4 cm, as those adopted throughout the experiments (Figure A).…”

Section: Methodsmentioning

confidence: 99%

“…17,18 Also, impinging jets 19 or fitting static mixers inside the pipeline allows fast homogenization of the reacting streams. 20,21 COBCs allow the attainment of turbulent flow regime by either periodic motion of intrinsic elements (moving baffles) within the pipe, 22 or by the periodic motion of the fluid against the internal static elements. 23 As such, mixing is provided by the generation and cessation of eddies when flow interacts with the restrictions (baffles).…”

Section: ■ Introductionmentioning

confidence: 99%

“…19,39 However, the small scale of the device has high risk of clogging, and its scale up is cumbersome. 40 Static mixers are a simpler easier-to-scale-up alternative, 21 offering significant practical advantage, similar to the COBC, of lower flow rates and longer residence times under plug flow conditions, mitigating the material consumption during early process development. 41−43 Alas, the achievement of fast mixing, despite allowing representative kinetics and control over the attributes of the product, does not obviate the prohibitive material requirements of continuous experiments.…”

Section: ■ Introductionmentioning

confidence: 99%

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Loop-Configuration for Plug Flow Crystallization Process Development

Aprile,

Pandit,

Albertazzi

et al. 2023

Crystal Growth & Design

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Continuous crystallization plays a pivotal role in the transition to continuous manufacturing that the pharmaceutical industry is currently undertaking. Alas, the development of a continuous crystallization process using data from continuous operation is prohibitively material-intensive. Given the state of control nature of the continuous formalism, experimental design spaces entail several experiments, in which up to ten residence times are required to assess an experimental condition at steady state. Furthermore, transferring batch kinetics determined from batch experiments to a continuous crystallizer, despite being common practice, adds undesirable uncertainty to the development endeavors due to equipment-dependent mass and heat transfer. In this work, we present a novel configuration of a tubular crystallizer, capable of characterizing a system with a few experiments, curbing the reactor footprint, and abating the development's raw material requirements. A stream of crystallizing material, flowing inside a tubular crystallizer equipped with Kenics static mixers, was fully recirculated, implementing a looped plug flow configuration, and its evolution was monitored in-line continuously by means of in situ Process Analytical Technologies. This allows effective mimicking of long residence times (which correspond to large process volumes) in a short plug flow crystallizer while maintaining plug flow conditions and screening a process from nucleation to equilibrium. Computational fluid dynamics simulations supported the assumption of negligible back mixing and aided the comparison of the mixing with that of a cascade of continuous stirred tank reactors. The use of the novel configuration is showcased for the antisolvent crystallizations of ketoconazole, azithromycin, and glycine. Using this approach, we show reductions in raw material requirements from 50 to 98%, compared with an equivalent standard plug flow crystallizer. Naturally, the configuration can also be employed for manufacturing in a semicontinuous manner.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Loop-Configuration for Plug Flow Crystallization Process Development

Aprile,

Pandit,

Albertazzi

et al. 2023

Crystal Growth & Design

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“…Plug flow reactors typically employ a variety of static mixers to ensure good mass transfer, reducing agglomeration and improving suspension of solids. Inserts or 3D printed reactors with inbuilt static mixers can help suspend and mix slurries with optimal operation directly linked to flow rate . Oscillatory baffled reactors (OBRs) comprise a series of single- or multi-orifice baffles and typically use piston-driven oscillatory flow to generate eddies in the reactor .…”

Section: Solids–the Nemesis Of the Flow Chemist?mentioning

confidence: 99%

Quid Pro Flow

2023

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How do you get into flow? We trained in flow chemistry during postdoctoral research and are now applying it in new areas: materials chemistry, crystallization, and supramolecular synthesis. Typically, when researchers think of "flow", they are considering predominantly liquid-based organic synthesis; application to other disciplines comes with its own challenges. In this Perspective, we highlight why we use and champion flow technologies in our fields, summarize some of the questions we encounter when discussing entry into flow research, and suggest steps to make the transition into the field, emphasizing that communication and collaboration between disciplines is key.

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Experimental study on energy consumption characteristics of rotational–perforated static mixers

et al. 2023

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An ideal static mixer can achieve efficient mixing at low pressure drops. Owing to the excellent performance of the tridimensional rotational flow sieve tray (TRST) in a gas–liquid two‐phase system, the TRST structure was modified into a rotational–perforated static mixer (RPSM) to enhance mixing in multicomponent liquid systems. The energy consumption characteristics of the RPSM were experimentally studied based on Reynolds numbers in the range of 986–7892, gap L = 0–80 mm, and relative angle γ = 0–45°. The effects of the element installation method, number, gap, relative angle, fluid Reynolds number, fluid properties, and other parameters on the RPSM pressure drop were also investigated. An interaction analysis of each factor was performed using the factorial design method and an empirical model of the RPSM Z‐factor was established. Additionally, pressure drop in the RPSM was compared with those of other commonly used static mixers. Results show that, when the element is backward‐installed, the pressure drop is higher than that in the forward direction because the fluid is constantly twisted. Moreover, the pressure drop increases with increasing element gap, and the average increase is 43.64% and 19.28% for the forward and backward installations, respectively. The influence of the relative angle on the pressure drop is mainly reflected when the gap L = 0. Subsequently, the degree of influence of each factor was determined, and the Z‐factor was calculated and found to be consistent with the experimental values (relative error of less than 15%).

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Design and characterization of Kenics static mixer crystallizers

Cited by 20 publications

References 72 publications

Loop-Configuration for Plug Flow Crystallization Process Development

Loop-Configuration for Plug Flow Crystallization Process Development

Quid Pro Flow

Experimental study on energy consumption characteristics of rotational–perforated static mixers

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