Establishment of a continuous sonocrystallization process for lactose in an oscillatory baffled crystallizer

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Abstract

Crystallization at production scale (>10 kg) is typically a poorly understood unit operation with limited application of first-principles understanding of crystallization to routine design, optimization, and control. In this study, a systematic approach has been established to transfer an existing batch process enabling the implementation of a continuous process in an oscillatory baffled crystallizer (OBC) using ultrasound. Process analytical technology (PAT) was used to understand and monitor the process. Kinetic and thermodynamic parameters have been investigated for lactose sonocrystallization using focused beam reflectance measurement (FBRM) (Mettler Toledo) and mid-infrared spectroscopy (mid-IR) (ABB) in a multiorifice batch oscillatory baffled crystallizer (Batch-OBC). This platform provides an ideal mimic of the mixing, hydrodynamics and operating conditions of the continuous oscillatory flow crystallizer (COBC) while requiring only limited material. Full characterization of the hydrodynamics of the COBC was carried out to identify conditions that deliver plug-flow behavior with residence times of 1–5 h. The results show that continuous crystallization offers significant advantages in terms of process outcomes and operability, including particle size distribution (mean particle size <1500 μm) of alpha lactose monohydrate (ALM), as well as reduced cycle time (4 h compared to the 13–20 h in a batch process). Continuous sonocrystallization was performed for the first time at a throughput of 356 g·h–1 for 12–16 h. During the run at near plug flow, with supersaturation and controlled nucleation using sonication, no issues with fouling or agglomeration were observed. This approach has demonstrated the capability to provide close control of particle attributes at an industrially relevant scale.
LanguageEnglish
Pages1871-1881
Number of pages11
JournalOrganic Process Research and Development
Volume19
Issue number12
Early online date20 Nov 2015
DOIs
Publication statusPublished - 18 Dec 2015

Fingerprint

lactose
Crystallizers
Lactose
Crystallization
Hydrodynamics
crystallization
plugs
Particle Size
hydrodynamics
Sonication
fouling
Reflectometers
Supersaturation
design optimization
supersaturation
agglomeration
Fouling
particle size distribution
Thermodynamics
Particle size analysis

Keywords

  • crystallization
  • process analytical technology
  • oscillatory baffled crystallizer
  • ultrasound
  • mid infrared spectroscopy

Cite this

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title = "Establishment of a continuous sonocrystallization process for lactose in an oscillatory baffled crystallizer",
abstract = "Crystallization at production scale (>10 kg) is typically a poorly understood unit operation with limited application of first-principles understanding of crystallization to routine design, optimization, and control. In this study, a systematic approach has been established to transfer an existing batch process enabling the implementation of a continuous process in an oscillatory baffled crystallizer (OBC) using ultrasound. Process analytical technology (PAT) was used to understand and monitor the process. Kinetic and thermodynamic parameters have been investigated for lactose sonocrystallization using focused beam reflectance measurement (FBRM) (Mettler Toledo) and mid-infrared spectroscopy (mid-IR) (ABB) in a multiorifice batch oscillatory baffled crystallizer (Batch-OBC). This platform provides an ideal mimic of the mixing, hydrodynamics and operating conditions of the continuous oscillatory flow crystallizer (COBC) while requiring only limited material. Full characterization of the hydrodynamics of the COBC was carried out to identify conditions that deliver plug-flow behavior with residence times of 1–5 h. The results show that continuous crystallization offers significant advantages in terms of process outcomes and operability, including particle size distribution (mean particle size <1500 μm) of alpha lactose monohydrate (ALM), as well as reduced cycle time (4 h compared to the 13–20 h in a batch process). Continuous sonocrystallization was performed for the first time at a throughput of 356 g·h–1 for 12–16 h. During the run at near plug flow, with supersaturation and controlled nucleation using sonication, no issues with fouling or agglomeration were observed. This approach has demonstrated the capability to provide close control of particle attributes at an industrially relevant scale.",
keywords = "crystallization, process analytical technology, oscillatory baffled crystallizer, ultrasound, mid infrared spectroscopy",
author = "Humera Siddique and Brown, {Cameron J.} and Ian Houson and Florence, {Alastair J.}",
note = "This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Process Research and Development, {\circledC} American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.oprd.5b00127",
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TY - JOUR

T1 - Establishment of a continuous sonocrystallization process for lactose in an oscillatory baffled crystallizer

AU - Siddique, Humera

AU - Brown, Cameron J.

AU - Houson, Ian

AU - Florence, Alastair J.

N1 - This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Process Research and Development, © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.oprd.5b00127

PY - 2015/12/18

Y1 - 2015/12/18

N2 - Crystallization at production scale (>10 kg) is typically a poorly understood unit operation with limited application of first-principles understanding of crystallization to routine design, optimization, and control. In this study, a systematic approach has been established to transfer an existing batch process enabling the implementation of a continuous process in an oscillatory baffled crystallizer (OBC) using ultrasound. Process analytical technology (PAT) was used to understand and monitor the process. Kinetic and thermodynamic parameters have been investigated for lactose sonocrystallization using focused beam reflectance measurement (FBRM) (Mettler Toledo) and mid-infrared spectroscopy (mid-IR) (ABB) in a multiorifice batch oscillatory baffled crystallizer (Batch-OBC). This platform provides an ideal mimic of the mixing, hydrodynamics and operating conditions of the continuous oscillatory flow crystallizer (COBC) while requiring only limited material. Full characterization of the hydrodynamics of the COBC was carried out to identify conditions that deliver plug-flow behavior with residence times of 1–5 h. The results show that continuous crystallization offers significant advantages in terms of process outcomes and operability, including particle size distribution (mean particle size <1500 μm) of alpha lactose monohydrate (ALM), as well as reduced cycle time (4 h compared to the 13–20 h in a batch process). Continuous sonocrystallization was performed for the first time at a throughput of 356 g·h–1 for 12–16 h. During the run at near plug flow, with supersaturation and controlled nucleation using sonication, no issues with fouling or agglomeration were observed. This approach has demonstrated the capability to provide close control of particle attributes at an industrially relevant scale.

AB - Crystallization at production scale (>10 kg) is typically a poorly understood unit operation with limited application of first-principles understanding of crystallization to routine design, optimization, and control. In this study, a systematic approach has been established to transfer an existing batch process enabling the implementation of a continuous process in an oscillatory baffled crystallizer (OBC) using ultrasound. Process analytical technology (PAT) was used to understand and monitor the process. Kinetic and thermodynamic parameters have been investigated for lactose sonocrystallization using focused beam reflectance measurement (FBRM) (Mettler Toledo) and mid-infrared spectroscopy (mid-IR) (ABB) in a multiorifice batch oscillatory baffled crystallizer (Batch-OBC). This platform provides an ideal mimic of the mixing, hydrodynamics and operating conditions of the continuous oscillatory flow crystallizer (COBC) while requiring only limited material. Full characterization of the hydrodynamics of the COBC was carried out to identify conditions that deliver plug-flow behavior with residence times of 1–5 h. The results show that continuous crystallization offers significant advantages in terms of process outcomes and operability, including particle size distribution (mean particle size <1500 μm) of alpha lactose monohydrate (ALM), as well as reduced cycle time (4 h compared to the 13–20 h in a batch process). Continuous sonocrystallization was performed for the first time at a throughput of 356 g·h–1 for 12–16 h. During the run at near plug flow, with supersaturation and controlled nucleation using sonication, no issues with fouling or agglomeration were observed. This approach has demonstrated the capability to provide close control of particle attributes at an industrially relevant scale.

KW - crystallization

KW - process analytical technology

KW - oscillatory baffled crystallizer

KW - ultrasound

KW - mid infrared spectroscopy

UR - http://pubs.acs.org/journal/oprdfk

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DO - 10.1021/acs.oprd.5b00127

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EP - 1881

JO - Organic Process Research and Development

T2 - Organic Process Research and Development

JF - Organic Process Research and Development

SN - 1083-6160

IS - 12

ER -