Abstract

Size and shape distributions are among critical quality attributes of particulate products and their inline measurement is crucial for monitoring and control of particle manufacturing processes. This requires advanced tools that can estimate particle size and shape distributions from multi-sensor data captured in situ across various processing steps.

In this work, we study changes in size and shape distributions, as well as number of particles during high shear wet milling, which is increasingly being employed for size reduction in crystalline slurries in pharmaceutical processing. Saturated suspensions of benzoic acid, paracetamol and metformin hydrochloride were used in this study. We employ our recently developed tools for estimating particle aspect ratio and particle size distributions from chord length distribution (CLD) measurements and imaging. We also compare estimated particle size distributions from CLD and imaging with corresponding estimates from offline instruments.

The results show that these tools are capable of quantitatively capturing changes in particle sizes and shape during wet milling inline. This is the first time that such a capability has been reported in the literature. The ability to quantitatively monitor particle size and shape distributions in real time will enable development of more realistic and accurate population balance models of wet milling and crystallisation, and aid more efficient control of crystallisation processes.
LanguageEnglish
Pages2987-2995
Number of pages9
JournalAdvanced Powder Technology
Volume29
Issue number12
Early online date15 Sep 2018
DOIs
Publication statusPublished - 31 Dec 2018

Fingerprint

Slurries
Particle size
Crystallization
Particle size analysis
Crystals
Sensors
Imaging techniques
Benzoic Acid
Benzoic acid
Metformin
Acetaminophen
Processing
Drug products
Particles (particulate matter)
Aspect ratio
Suspensions
Crystalline materials
Monitoring
Pharmaceutical Preparations

Keywords

  • particle size distribution
  • chord length distribution
  • wet milling

Cite this

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title = "Multi-sensor inline measurements of crystal size and shape distributions during high shear wet milling of crystal slurries",
abstract = "Size and shape distributions are among critical quality attributes of particulate products and their inline measurement is crucial for monitoring and control of particle manufacturing processes. This requires advanced tools that can estimate particle size and shape distributions from multi-sensor data captured in situ across various processing steps. In this work, we study changes in size and shape distributions, as well as number of particles during high shear wet milling, which is increasingly being employed for size reduction in crystalline slurries in pharmaceutical processing. Saturated suspensions of benzoic acid, paracetamol and metformin hydrochloride were used in this study. We employ our recently developed tools for estimating particle aspect ratio and particle size distributions from chord length distribution (CLD) measurements and imaging. We also compare estimated particle size distributions from CLD and imaging with corresponding estimates from offline instruments.The results show that these tools are capable of quantitatively capturing changes in particle sizes and shape during wet milling inline. This is the first time that such a capability has been reported in the literature. The ability to quantitatively monitor particle size and shape distributions in real time will enable development of more realistic and accurate population balance models of wet milling and crystallisation, and aid more efficient control of crystallisation processes.",
keywords = "particle size distribution, chord length distribution, wet milling",
author = "Agimelen, {Okpeafoh S.} and Vaclav Svoboda and Bilal Ahmed and Javier Cardona and Jerzy Dziewierz and Brown, {Cameron J.} and Thomas McGlone and Alison Cleary and Christos Tachtatzis and Craig Michie and Florence, {Alastair J.} and Ivan Andonovic and Mulholland, {Anthony J.} and Jan Sefcik",
year = "2018",
month = "12",
day = "31",
doi = "10.1016/j.apt.2018.09.003",
language = "English",
volume = "29",
pages = "2987--2995",
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TY - JOUR

T1 - Multi-sensor inline measurements of crystal size and shape distributions during high shear wet milling of crystal slurries

AU - Agimelen, Okpeafoh S.

AU - Svoboda, Vaclav

AU - Ahmed, Bilal

AU - Cardona, Javier

AU - Dziewierz, Jerzy

AU - Brown, Cameron J.

AU - McGlone, Thomas

AU - Cleary, Alison

AU - Tachtatzis, Christos

AU - Michie, Craig

AU - Florence, Alastair J.

AU - Andonovic, Ivan

AU - Mulholland, Anthony J.

AU - Sefcik, Jan

PY - 2018/12/31

Y1 - 2018/12/31

N2 - Size and shape distributions are among critical quality attributes of particulate products and their inline measurement is crucial for monitoring and control of particle manufacturing processes. This requires advanced tools that can estimate particle size and shape distributions from multi-sensor data captured in situ across various processing steps. In this work, we study changes in size and shape distributions, as well as number of particles during high shear wet milling, which is increasingly being employed for size reduction in crystalline slurries in pharmaceutical processing. Saturated suspensions of benzoic acid, paracetamol and metformin hydrochloride were used in this study. We employ our recently developed tools for estimating particle aspect ratio and particle size distributions from chord length distribution (CLD) measurements and imaging. We also compare estimated particle size distributions from CLD and imaging with corresponding estimates from offline instruments.The results show that these tools are capable of quantitatively capturing changes in particle sizes and shape during wet milling inline. This is the first time that such a capability has been reported in the literature. The ability to quantitatively monitor particle size and shape distributions in real time will enable development of more realistic and accurate population balance models of wet milling and crystallisation, and aid more efficient control of crystallisation processes.

AB - Size and shape distributions are among critical quality attributes of particulate products and their inline measurement is crucial for monitoring and control of particle manufacturing processes. This requires advanced tools that can estimate particle size and shape distributions from multi-sensor data captured in situ across various processing steps. In this work, we study changes in size and shape distributions, as well as number of particles during high shear wet milling, which is increasingly being employed for size reduction in crystalline slurries in pharmaceutical processing. Saturated suspensions of benzoic acid, paracetamol and metformin hydrochloride were used in this study. We employ our recently developed tools for estimating particle aspect ratio and particle size distributions from chord length distribution (CLD) measurements and imaging. We also compare estimated particle size distributions from CLD and imaging with corresponding estimates from offline instruments.The results show that these tools are capable of quantitatively capturing changes in particle sizes and shape during wet milling inline. This is the first time that such a capability has been reported in the literature. The ability to quantitatively monitor particle size and shape distributions in real time will enable development of more realistic and accurate population balance models of wet milling and crystallisation, and aid more efficient control of crystallisation processes.

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KW - chord length distribution

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