Quantifying crystallisation rates of amorphous pharmaceuticals with dynamic mechanical analysis (DMA)

Area of Science:

• Pharmaceutical Science
• Materials Science
• Physical Chemistry

Background:

• Amorphous pharmaceuticals are prone to phase transformation into crystalline forms, impacting stability.
• Dynamic mechanical analysis (DMA) is explored as a stability-indicating assay for complex pharmaceutical formulations.
• Understanding crystallization mechanisms is crucial for predicting and controlling drug product stability.

Purpose of the Study:

• To evaluate dynamic mechanical analysis (DMA) as a stability-indicating assay for amorphous pharmaceuticals.
• To investigate the influence of temperature and relative humidity (RH) on the rate and mechanism of amorphous indomethacin crystallization.
• To quantitatively determine crystallization kinetics using the Urbanovici-Segal model.

Main Methods:

• Amorphous indomethacin samples were prepared and mounted in DMA equipment with controlled RH exposure.
• Crystallization was monitored by changes in the storage modulus over time.
• Data was converted to fraction crystallized to apply the Urbanovici-Segal model for kinetic analysis.

Main Results:

• Crystallization onset was detected as an increase in storage modulus.
• Crystallization rates increased with temperature and humidity.
• Temperature and humidity significantly affected crystallization mechanisms, including 3D growth, edge growth, and mixed surface/edge growth.

Conclusions:

• DMA is a viable method for monitoring amorphous pharmaceutical crystallization and determining kinetics.
• Environmental factors like temperature and humidity play a critical role in both the rate and mechanism of crystallization.
• Further studies are needed to optimize DMA for quantitative analysis in complex formulations like oral films.