Extraordinary Long-Term-Stability in Kinetically Stabilized Amorphous Solid Dispersions of Fenofibrate

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Amorphous solid dispersions (ASDs) are crucial for enhancing drug bioavailability but face challenges with recrystallization.
• The long-term physical stability of ASDs, particularly their resistance to crystallization, remains a critical area of investigation.
• Recrystallization can compromise drug efficacy by reducing bioavailability and potentially lowering the effective dose.

Purpose of the Study:

• To investigate the long-term physical stability of a kinetically stabilized amorphous solid dispersion (ASD) of fenofibrate.
• To assess the potential for recrystallization in ASD formulations over an extended storage period (15 years).
• To evaluate the efficacy of kinetic stabilization in preventing drug crystallization in ASDs.

Main Methods:

• Physicochemical characterization of a 15-year-old fenofibrate ASD formulation compared to a fresh batch.
• Assessment of crystallinity using polarized light microscopy (PLM) and X-ray powder diffraction (XRPD).
• Investigation of crystal growth kinetics via transmission Raman spectroscopy (TRS) to develop a predictive model.

Main Results:

• The 15-year-old fenofibrate ASD formulation remained physically stable and amorphous.
• Comprehensive characterization confirmed content, purity, water content, and glass transition properties were maintained.
• The developed predictive model successfully forecasted the amorphous state of the aged ASD samples.

Conclusions:

• Kinetic stabilization alone is sufficient to prevent crystallization in ASDs over prolonged storage periods (at least 15 years).
• This study demonstrates the potential for long-term physical stability in certain ASD formulations.
• The findings suggest a need to re-evaluate the perceived risk of recrystallization in kinetically stabilized ASDs.