Stabilization of the Amorphous Ezetimibe Drug by Confining Its Dimension

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Amorphous solid dispersions are crucial for enhancing the bioavailability of poorly soluble drugs like ezetimibe.
• Physical stability of amorphous drugs is a key challenge, often leading to recrystallization and reduced efficacy.

Purpose of the Study:

• To investigate the effect of nanoconfinement on the molecular mobility and physical stability of amorphous ezetimibe.
• To explore the role of host material pore size in preventing ezetimibe recrystallization.

Main Methods:

• Preparation of ezetimibe-loaded guest/host systems (Aeroperl 300 and Neusilin US2).
• Characterization using X-ray diffraction (XRD), differential scanning calorimetry (DSC), and broadband dielectric spectroscopy (BDS).

Main Results:

• Molecular mobility of ezetimibe within nanopores is highly dependent on host pore size.
• Ezetimibe confined in larger pores (30 nm) showed a tendency to recrystallize.
• Ezetimibe confined in smaller pores (5 nm) remained amorphous and stable, preventing crystallization.

Conclusions:

• Nanoconfinement in small pores (<5 nm) effectively stabilizes amorphous ezetimibe against recrystallization.
• Stabilization is attributed to altered molecular dynamics, pore wall immobilization, and pore size being smaller than critical crystal nuclei size.