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

Thai T. H. Nguyen, Azeem Khan, Layla M. Bruce, Clarissa Forbes, Richard L. O'Leary, Chris J. Price

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
145 Downloads (Pure)


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%.
Original languageEnglish
Article number294
Number of pages24
Issue number10
Publication statusPublished - 30 Sept 2017


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


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