Effects of a structurally related substance on the crystallization of paracetamol

Ali SALEEMI, I.I. ONYEMELUKWE, Zoltan NAGY

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PDF(653 KB)
Front. Chem. Sci. Eng. ›› 2013, Vol. 7 ›› Issue (1) : 79-87. DOI: 10.1007/s11705-013-1308-7
RESEARCH ARTICLE

Effects of a structurally related substance on the crystallization of paracetamol

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Abstract

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.

Keywords

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

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Ali SALEEMI, I.I. ONYEMELUKWE, Zoltan NAGY. Effects of a structurally related substance on the crystallization of paracetamol. Front Chem Sci Eng, 2013, 7(1): 79‒87 https://doi.org/10.1007/s11705-013-1308-7

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Acknowledgments

European Research Council Grant No. 280106+ CrySys and Engineering and Physical Science Research Council, UK, Centre for Continuous Manufacturing and Crystallization.
Nomenclature
τInduction time to nucleation
JRate of nucleation
γSurface free energy between the nucleus and supersaturated solution
VMolecular volume
TTemperature or absolute temperature
TsetSetpoint temperature
TlimNucleation temperature
ΔTmaxMaximum supercooling
T0Saturation temperature
APre-exponential factor
kBBoltzmann constant
ΔθDegree of undercooling
SSupersaturation or absolute supersaturation
SseSetpoint supersaturation
CSolution concentration
CsolEquilibrium solubility
csEquilibrium solubility
cConcentration at 45°C
RCooling rate
r*Radius of critical nucleus

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