Microscopic Cracks Modulate Nucleation and Solid-State Crystallization Tendency of Amorphous Celecoxib.

Area of Science:

• Solid-state chemistry
• Pharmaceutical sciences
• Materials science

Background:

• Drugs are classified by crystallization tendency (fast, moderate, poor) using heat-cool-heat protocols.
• Amorphous drug stabilization strategies rely on understanding crystallization.
• Microscopic sample characteristics are often overlooked in crystallization studies.

Purpose of the Study:

• To investigate the impact of microscopic cracks on the crystallization tendency of amorphous celecoxib.
• To determine if crack formation influences drug classification and stability.

Main Methods:

• Differential scanning calorimetry (DSC) heat-cool-heat protocol.
• Nanoindentation for mechanical property analysis.
• Nuclei nourishment experiments and Raman spectroscopy.

Main Results:

• Cracks formed between 0-10 °C during cooling initiated amorphous celecoxib crystallization.
• Nanoindentation showed inhomogeneous mechanical properties in cracked samples.
• Evidence of crack-assisted nucleation and altered intermolecular interactions was observed.

Conclusions:

• Microscopic cracks can significantly influence the crystallization tendency of amorphous drugs.
• The presence or absence of cracks may change the classification of amorphous celecoxib.
• Subtle physical events like microcracks require consideration for accurate drug crystallization tendency assessment and stabilization.