Seed loading effects on the mean crystal size of acetylsalicylic acid in a continuous‐flow crystallization device

Eder, Rafael Johannes-Paul; Schmitt, Elisabeth; Grill, Julia; Radl, Stefan; Gruber‐Wölfler, Heidrun; Khinast, Johannes G.

doi:10.1002/crat.201000634

Cited by 85 publications

(99 citation statements)

References 49 publications

(71 reference statements)

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“…The particle size distribution (PSD) of the produced crystals affects downstream processes such as filtration, milling, and formulation [1,5]. Furthermore, the solubility, disintegration, and dissolution rate of medicines in the human body depend on this parameter [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

et al. 2017

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Controlling particle size is essential for crystal quality in the chemical and pharmaceutical industry. Several articles illustrate the potential of ultrasound to tune this particle size during the crystallization process. This paper investigates how ultrasound can control the particle size distribution (PSD) of acetaminophen crystals by continuous seed generation in a tubular crystallizer followed by batch growth. It is demonstrated that the supersaturation ratio at which ultrasound starts seed generation has a substantial effect on the final PSD while the applied power is insignificant in the studied conditions. The higher the supersaturation ratio, the smaller the final crystals become up to a supersaturation ratio of 1.56. Furthermore, it was shown that ultrasound can also impact the final PSD when applied during the growth phase. Frequencies of 850 kHz or below reduce the final particle size; the lower the applied frequency, the smaller the crystals become. In conclusion, one could state that ultrasound is able to control the particle size during seed generation and subsequent growth until the final particle size.

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Section: Introductionmentioning

confidence: 99%

“…Particle size control is extremely important during crystallization processes in the chemical and pharmaceutical industry [1][2][3][4]. The particle size distribution (PSD) of the produced crystals affects downstream processes such as filtration, milling, and formulation [1,5].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

et al. 2017

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“…Continuously seeded cooling crystallization can suppress undesired nucleation events or the formation of crystals of an undesired morphology. Thus, a stable steadystate operation is feasible and scaling/clogging issues can be reduced [49,92,103]. The current work focuses on the development of a device for continuous seed crystal generation by abrasion from larger parent or product crystals, followed by a mechanical classification of the desired crystal fraction.…”

Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

Separation Units and Equipment for Lab-Scale Process Development

Hohmann¹,

Kurt²,

Soboll³

et al. 2016

J Flow Chem

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For complete chemical processes, downstream operation steps are essential, but on a miniaturized scale, they are not so far developed as the microreactors. This contribution presents three different unit operations for phase and component separation. Liquid-liquid extraction is often performed in columns, which were miniaturized for higher separation efficiency and flow rates suitable for processes in flow chemistry. Two-phase mass transfer processes in capillaries benefit from rapid final phase separation, which can be performed in an in-line phase splitter based on different surface wetting behavior. Crystallization is often a final purification step, which is performed in a continuously operated helical tube setup with narrow residence time distribution. For all unit operations, design criteria are shown with typical applications. The methodology of downscaling of known equipment and employing typical microscale phenomena such as good flow control, laminar flow, or dominant surface forces leads to successful equipment design.

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“…For example, Lawton et al 17 reported the application of a continuous oscillatory 5 baffled crystallizer (COBC) for a cooling crystallization which offered significant advantages in operating cost and processing time. Eder [18][19] and his colleagues investigated the impacts of flow rate and seed loading in continuously-seeded tubular cooling crystallizers for the production of active pharmaceutical ingredients (APIs). Ferguson et al 20 reported the employment of a variety of process analytical technology (PAT) tools for particle size and solute concentration measurement in a plug flow crystallizer.…”

Section: Introductionmentioning

confidence: 99%

Mathematical Modeling, Design, and Optimization of a Multisegment Multiaddition Plug-Flow Crystallizer for Antisolvent Crystallizations

Benyahia

Nagy

et al. 2015

Org. Process Res. Dev.

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Just Accepted "Just Accepted" manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides "Just Accepted" as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. "Just Accepted" manuscripts appear in full in PDF format accompanied by an HTML abstract. "Just Accepted" manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). "Just Accepted" is an optional service offered to authors. Therefore, the "Just Accepted" Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the "Just Accepted" Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these "Just Accepted" manuscripts. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2 TABLE OF CONTENTS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 The configuration in which anti-solvent could be added at a variety of different locations along the tube length and at optimal flow rates was able to outperform previous designs in the literature which considered equally-spaced anti-solvent additions. The use of dynamic models to detect problems during startup of an MSMA-PFC was also highlighted.

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Seed loading effects on the mean crystal size of acetylsalicylic acid in a continuous‐flow crystallization device

Cited by 85 publications

References 49 publications

Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

Separation Units and Equipment for Lab-Scale Process Development

Mathematical Modeling, Design, and Optimization of a Multisegment Multiaddition Plug-Flow Crystallizer for Antisolvent Crystallizations

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