Mechanism for Stabilizing an Amorphous Drug Using Amino Acids within Co-Amorphous Blends

Area of Science:

• Pharmaceutical Science
• Materials Science
• Physical Chemistry

Background:

• Co-amorphous formulations are key to enhancing the bioavailability of poorly soluble drugs.
• Amino acids are frequently explored as co-formers for stabilizing amorphous drug states.
• Understanding the stabilization mechanism is crucial for rational co-amorphous design.

Purpose of the Study:

• To investigate the thermal stability of indomethacin co-amorphous blends with various amino acids.
• To elucidate the role of amino acids in stabilizing the amorphous state of indomethacin.
• To explore the relationship between blend properties and the drug's hydrogen-bond network.

Main Methods:

• Cryo-milling was used to prepare co-amorphous indomethacin-amino acid blends.
• Low- and mid-frequency Raman spectroscopy were employed for analysis.
• Thermal stability of the amorphous formulations was assessed.

Main Results:

• L-arginine demonstrated a remarkable ability to stabilize amorphous indomethacin.
• A stiffening of the hydrogen-bond network in amorphous indomethacin was observed with L-arginine.
• Raman spectroscopy provided insights into the physical properties and hydrogen-bond network interactions.

Conclusions:

• Amino acids can act as effective stiffeners for the hydrogen-bond network of indomethacin.
• L-arginine significantly enhances the amorphous stability of indomethacin.
• This study suggests a new approach for designing stable co-amorphous drug formulations.