Effects of a structurally related substance on the crystallization of paracetamol

Ali Saleemi, I. I. Onyemelukwe, Zoltan Nagy

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Paracetamol (PCM) was crystallized from an isopropanol (IPA) solution containing various small amounts of metacetamol as an additive. The effect on the nucleation kinetics was studied by measuring the induction time to nucleation and the metastable zone width using focused beam reflectance measurements (FBRM) and attenuated total reflectance (ATR-UV/Vis) spectroscopy. Both the induction time and the metastable zone width were expressed as functions of the additive concentration. Small amounts of metacetamol (1-4 mol-%) were found to cause significant inhibition to the nucleation by extending both the induction time and the metastable zone width. A progressive change in the morphology of the paracetamol crystals from tabular to columnar habit was observed with increasing metacetamol concentration. The solvent also had a significant effect on the size of the paracetamol crystals as smaller crystals were obtained in IPA than in aqueous solution. The dissolution rate of paracetamol was improved by the incorporation of metacetamol with 4 mol-% having the most effect. A supersaturation control (SSC) approach was implemented for the PCM-IPA system with and without metacetamol in an attempt to control and obtain larger metacetamol-doped paracetamol crystals.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalFrontiers of Chemical Science and Engineering
Issue number1
Early online date25 Jan 2013
Publication statusPublished - Mar 2013
Externally publishedYes


  • acetaminophen
  • crystallization
  • induction time
  • metacetamol
  • metastable zone width
  • supersaturation control


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