Crystallization of undercooled liquid fenofibrate.

Area of Science:

• Pharmaceutical science
• Materials science
• Chemical engineering

Background:

• Amorphous drug formulations improve solubility and bioavailability of hydrophobic drugs.
• Crystallization of amorphous drugs during production and storage limits their therapeutic utility.
• Fenofibrate is a model hydrophobic drug often formulated in amorphous states.

Purpose of the Study:

• To investigate the crystallization behavior of undercooled liquid fenofibrate.
• To identify the rate-limiting steps in fenofibrate crystallization.
• To understand the factors contributing to the stability of amorphous fenofibrate.

Main Methods:

• Studying the crystallization kinetics of undercooled liquid fenofibrate.
• Analyzing nucleation and crystal growth processes.
• Observing the effect of seeding on crystallization.

Main Results:

• Nucleation is the rate-limiting step in fenofibrate crystallization.
• Crystal growth is rapid once initiated by seeding.
• Molecular incorporation into the crystal surface limits both nucleation and growth.
• These limitations contribute to the inherent stability of undercooled liquid fenofibrate.

Conclusions:

• The molecular incorporation process governs both nucleation and crystal growth in fenofibrate.
• Understanding these mechanisms enhances the stability of amorphous drug formulations.
• This research provides insights into stabilizing amorphous hydrophobic drugs against crystallization.