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Compression behavior of orthorhombic paracetamol

E Joiris1, P Di Martino, C Berneron

  • 1Laboratoire de Pharmacotechnie industrielle, Faculté des Sciences Pharmaceutiques et Biologiques de Lille II, France.

Pharmaceutical Research
|August 4, 1998
PubMed
Summary

Orthorhombic paracetamol demonstrates superior tabletability and plastic deformation compared to monoclinic paracetamol, making it ideal for direct compression processes due to its crystalline structure.

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Area of Science:

  • Pharmaceutical Sciences
  • Materials Science
  • Crystallography

Background:

  • Paracetamol (acetaminophen) is a widely used analgesic.
  • Polymorphism in paracetamol affects its physical and chemical properties.
  • Orthorhombic paracetamol crystals possess favorable technological properties for tablet manufacturing.

Purpose of the Study:

  • To investigate the compression behavior of orthorhombic paracetamol.
  • To compare the compression characteristics of orthorhombic and monoclinic paracetamol.
  • To elucidate the role of crystal structure, specifically sliding planes, in paracetamol's plasticity.

Main Methods:

  • Tablet compression of pure orthorhombic and monoclinic paracetamol using a single punch machine.
  • Analysis of Heckel's profiles to assess compression behavior.

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  • Scanning electron microscopy (SEM) to examine crystal deformation post-compression.

    • Main Results:

    • Orthorhombic paracetamol exhibited significantly better tabletability than the monoclinic form, with no capping observed.
    • Orthorhombic crystals showed increased fragmentation at low pressure and enhanced plastic deformation at high pressure.
    • SEM confirmed plastic deformation in orthorhombic paracetamol, with crystals folding under pressure, and lower elastic recovery during decompression.

    Conclusions:

    • Orthorhombic paracetamol is suitable for direct compression, unlike the monoclinic form.
    • The superior compression behavior of orthorhombic paracetamol is attributed to the presence of sliding planes in its crystal structure.
    • Understanding paracetamol polymorphism is crucial for optimizing pharmaceutical formulation and manufacturing.