Compression behavior of orthorhombic paracetamol

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.
• 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.