Indomethacin: The Interplay between Structural Relaxation, Viscous Flow and Crystal Growth

Area of Science:

• Materials Science
• Physical Chemistry
• Solid-State Chemistry

Background:

• Amorphous indomethacin undergoes structural relaxation, crystal growth, and decomposition.
• Particle size and heating rate are critical factors influencing these transformations.

Purpose of the Study:

• To investigate the impact of particle size and heating rate on the kinetics of amorphous indomethacin.
• To elucidate the mechanisms governing structural relaxation, crystal growth, and decomposition.
• To correlate macroscopic and microscopic crystal growth processes with molecular dynamics.

Main Methods:

• Non-isothermal differential scanning calorimetry (DSC) was employed.
• Varying particle sizes (d_aver) and heating rates (q⁺) were utilized.
• Apparent activation energies were calculated to characterize kinetic processes.

Main Results:

• Structural relaxation and decomposition kinetics were independent of particle size but dependent on heating rate.
• Crystal growth kinetics significantly influenced nucleation and the overall amorphous-to-crystalline transformation.
• Heating rate determined the polymorph formed: slow rates favored the stable γ-polymorph, while fast rates produced the metastable α-polymorph.

Conclusions:

• Heating rate is a key determinant of polymorph selection and crystallization kinetics in amorphous indomethacin.
• A link between viscosity, crystal growth, and structural relaxation dynamics was established.
• The study provides insights into distinguishing crystal growth modes in powdered materials.