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Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
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Crystallization and phase changes in paracetamol from the amorphous solid to the liquid phase.

Juraj Sibik1, Michael J Sargent, Miriam Franklin

  • 1Department of Chemical Engineering and Biotechnology, University of Cambridge , New Museums Site, Pembroke Street, Cambridge CB2 3RA, United Kingdom.

Molecular Pharmaceutics
|March 4, 2014
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Summary

Terahertz time-domain spectroscopy reveals paracetamol

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Area of Science:

  • Solid-state chemistry
  • Materials science
  • Spectroscopy

Background:

  • Amorphous paracetamol exists in a supercooled liquid state above room temperature.
  • Understanding phase transitions is crucial for pharmaceutical formulation and stability.

Purpose of the Study:

  • To characterize the solid and liquid phase dynamics of paracetamol using terahertz time-domain spectroscopy.
  • To investigate the crystallization kinetics of supercooled amorphous paracetamol.

Main Methods:

  • Terahertz time-domain spectroscopy (THz-TDS) was employed to monitor phase changes.
  • Differential scanning calorimetry (DSC) principles were applied to analyze thermal events.
  • The Avrami-Erofeev model was used for kinetic analysis.

Main Results:

  • Heating induced crystallization of amorphous paracetamol at 330 K, progressing through forms III, II, and I before melting at 455 K.
  • Distinct spectral features differentiated the supercooled liquid from its melt.
  • The onset of crystallization was quantified with an effective rate constant (k = 0.056 min⁻¹) at 329.5 K.

Conclusions:

  • THz-TDS is effective for characterizing paracetamol's solid and liquid phase dynamics.
  • The study provides detailed insights into the crystallization process and kinetics of amorphous paracetamol.
  • Established a quantitative understanding of paracetamol's phase transitions relevant to its solid-state properties.