The effect of ultrasound on the crystallisation of paracetamol in the presence of structurally similar impurities

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Abstract

Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size distribution determined by Focused Beam Reflectance Measurement (FBRM), crystal habit, filtration rate and impurity content in the crystal product by Liquid Chromatography-Mass Spectroscopy (LC-MS)) were investigated in bulk suspension crystallisation experiments with and without the use of ultrasound. The results demonstrate that ultrasonic intervention has a significant effect on both crystallisation and product crystal properties. It increases the nucleation rate resulting in smaller particles and a narrower Particle Size Distribution (PSD), the yield has been shown to be increase as has the product purity. The effect of ultrasound is to reduce the level acetanilide impurity incorporated during growth from a 2 mol% solution of the selected impurity from 0.85 mol% to 0.35 mol% and likewise ultrasound reduces the uptake of metacetamol from 1.88 mol% to 1.52 mol%.
LanguageEnglish
Number of pages24
JournalCrystals
DOIs
Publication statusPublished - 30 Sep 2017

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Acetaminophen
Crystallization
Ultrasonics
Impurities
crystallization
impurities
Crystals
crystals
products
purity
Nucleation
acetanilide
nucleation
Reflectometers
habits
Liquid chromatography
liquid chromatography
particle size distribution
Particle size analysis
Particles (particulate matter)

Keywords

  • suspension crystallisation
  • impurities
  • crystal size distribution
  • filtration rate
  • optical microscopy
  • image analysis
  • crystal morphology
  • purification
  • HPLC
  • ultrasound intensity

Cite this

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title = "The effect of ultrasound on the crystallisation of paracetamol in the presence of structurally similar impurities",
abstract = "Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size distribution determined by Focused Beam Reflectance Measurement (FBRM), crystal habit, filtration rate and impurity content in the crystal product by Liquid Chromatography-Mass Spectroscopy (LC-MS)) were investigated in bulk suspension crystallisation experiments with and without the use of ultrasound. The results demonstrate that ultrasonic intervention has a significant effect on both crystallisation and product crystal properties. It increases the nucleation rate resulting in smaller particles and a narrower Particle Size Distribution (PSD), the yield has been shown to be increase as has the product purity. The effect of ultrasound is to reduce the level acetanilide impurity incorporated during growth from a 2 mol{\%} solution of the selected impurity from 0.85 mol{\%} to 0.35 mol{\%} and likewise ultrasound reduces the uptake of metacetamol from 1.88 mol{\%} to 1.52 mol{\%}.",
keywords = "suspension crystallisation, impurities, crystal size distribution, filtration rate, optical microscopy, image analysis, crystal morphology, purification, HPLC, ultrasound intensity",
author = "Nguyen, {Thai T. H.} and Azeem Khan and Bruce, {Layla M.} and Clarissa Forbes and Richard O'Leary and Price, {Chris J.}",
year = "2017",
month = "9",
day = "30",
doi = "10.3390/cryst7100294",
language = "English",
journal = "Crystals",
issn = "2073-4352",

}

TY - JOUR

T1 - The effect of ultrasound on the crystallisation of paracetamol in the presence of structurally similar impurities

AU - Nguyen, Thai T. H.

AU - Khan, Azeem

AU - Bruce, Layla M.

AU - Forbes, Clarissa

AU - O'Leary, Richard

AU - Price, Chris J.

PY - 2017/9/30

Y1 - 2017/9/30

N2 - Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size distribution determined by Focused Beam Reflectance Measurement (FBRM), crystal habit, filtration rate and impurity content in the crystal product by Liquid Chromatography-Mass Spectroscopy (LC-MS)) were investigated in bulk suspension crystallisation experiments with and without the use of ultrasound. The results demonstrate that ultrasonic intervention has a significant effect on both crystallisation and product crystal properties. It increases the nucleation rate resulting in smaller particles and a narrower Particle Size Distribution (PSD), the yield has been shown to be increase as has the product purity. The effect of ultrasound is to reduce the level acetanilide impurity incorporated during growth from a 2 mol% solution of the selected impurity from 0.85 mol% to 0.35 mol% and likewise ultrasound reduces the uptake of metacetamol from 1.88 mol% to 1.52 mol%.

AB - Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size distribution determined by Focused Beam Reflectance Measurement (FBRM), crystal habit, filtration rate and impurity content in the crystal product by Liquid Chromatography-Mass Spectroscopy (LC-MS)) were investigated in bulk suspension crystallisation experiments with and without the use of ultrasound. The results demonstrate that ultrasonic intervention has a significant effect on both crystallisation and product crystal properties. It increases the nucleation rate resulting in smaller particles and a narrower Particle Size Distribution (PSD), the yield has been shown to be increase as has the product purity. The effect of ultrasound is to reduce the level acetanilide impurity incorporated during growth from a 2 mol% solution of the selected impurity from 0.85 mol% to 0.35 mol% and likewise ultrasound reduces the uptake of metacetamol from 1.88 mol% to 1.52 mol%.

KW - suspension crystallisation

KW - impurities

KW - crystal size distribution

KW - filtration rate

KW - optical microscopy

KW - image analysis

KW - crystal morphology

KW - purification

KW - HPLC

KW - ultrasound intensity

UR - http://www.mdpi.com/journal/crystals

U2 - 10.3390/cryst7100294

DO - 10.3390/cryst7100294

M3 - Article

JO - Crystals

T2 - Crystals

JF - Crystals

SN - 2073-4352

ER -