Recent progress of continuous crystallization

Wang, Ting; Lu, Haijiao; Wang, Jingkang; Xiao, Yan; Zhou, Yanan; Bao, Ying; Hao, Hongxun

doi:10.1016/j.jiec.2017.06.009

Cited by 102 publications

(81 citation statements)

References 214 publications

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“…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%

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: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…These design improvements may benefit from advanced process monitoring and control tools 3,47,54,56,131,135 (with suitable in-line process analytical technology 32,58,136 ) and predictive models 6,49,58,60,61,67,68,133,137,138 (based on deeper mechanistic understanding of the physical chemical phenomena). Process intensification strategies from existing crystallizers [1][2][3][4][5][6][7][8][9][10][11]139 (batch or continuous) can also be helpful for future improvement, including: (1) decoupling nucleation and growth; (2) exploiting multiphase hydrodynamics for enhanced mixing (Table 1 and section 3), e.g., oscillatory flow, Taylor flow, or slug flow with recirculation; 10 and (3) enhancing seeding control (section 4) and growth control (section 5), e.g., control crystal size in flow with wet milling, ultrasonication, micromixers, temperature cycling (fines removal), 10,29 and recycling method selection.…”

Section: Outlook and Future Perspectivesmentioning

confidence: 99%

Designs of continuous-flow pharmaceutical crystallizers: developments and practice

Jiang

Braatz

2019

CrystEngComm

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“…In general, continuous crystallization is performed in two basic apparatuses, namely, on the one hand in the continuously stirred tank (CST), especially the mixed-suspension, mixedproduct-removal (MSPMR) [26][27][28][29][30], and on the other hand in the plug flow (PF) [31][32][33][34][35][36][37][38]. There are many variants of both types, which are described in literature [39,40].…”

Section: Tubular Crystallizermentioning

confidence: 99%

Equipment and Separation Units for Flow Chemistry Applications and Process Development

et al. 2019

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Process development and small‐scale production gets more and more important in fine chemistry and pharmaceutical production. An equipment toolbox assists process synthesis presented in this contribution. A microfluidic calorimeter can measure kinetic and thermodynamic reaction data with commercial plate reactors. A tubular reactor coiled with 90° bends allows for long residence time with low axial dispersion, also known as coiled flow inverter (CFI). A similar setup is used for continuous‐flow cooling crystallization. Small‐scale columns with rotating internals are employed for distillation and liquid‐liquid extraction. Main emphasis will be put on automation and scale‐up in future steps.

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Recent progress of continuous crystallization

Cited by 102 publications

References 214 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

Designs of continuous-flow pharmaceutical crystallizers: developments and practice

Equipment and Separation Units for Flow Chemistry Applications and Process Development

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