Different or the same? exploring the physicochemical properties and molecular mobility of celecoxib amorphous forms

Area of Science:

• Pharmaceutical Science
• Materials Science
• Solid-State Chemistry

Background:

• Polyamorphism in amorphous pharmaceutical solids is a critical area of research.
• Understanding the influence of preparation methods on amorphous solid forms is essential for drug development.

Purpose of the Study:

• To investigate the potential for polyamorphism in amorphous celecoxib (CEL).
• To analyze the impact of quench-cooling (QC), ball milling (BM), and spray drying (SD) on CEL's physicochemical properties.

Main Methods:

• Modulated differential scanning calorimetry (mDSC) for thermal behavior.
• Powder morphology analysis.
• Molecular dynamics simulations.
• Quantum mechanical calculations.
• Pair distribution function (PDF) analysis.
• Isothermal microcalorimetry.

Main Results:

• Amorphous CEL forms (CEL-QC, CEL-BM, CEL-SD) showed similar glass transition temperatures but distinct recrystallization behaviors and morphologies.
• Molecular dynamics simulations revealed similar molecular conformational distributions for CEL prepared via QC and SD, differing from crystalline forms.
• Hydrogen bonding, local structures, and relaxation times were comparable across the amorphous forms.

Conclusions:

• Despite differing recrystallization patterns, the investigated amorphous celecoxib forms did not exhibit polyamorphism.
• Physicochemical properties and molecular conformations were largely consistent across preparation methods.