Mechanochemically Induced Solid-State Transformations of Levofloxacin.

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Materials Science

Background:

• Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone with multiple solid forms.
• Understanding solid-state transformations is crucial for drug formulation and stability.

Purpose of the Study:

• To investigate the amorphization capabilities and solid-state transformations of LVXh using ball milling.
• To compare ball milling with spray drying for amorphous levofloxacin (LVXam) formation.
• To elucidate the mechanism of LVXam formation via mechanical treatment.

Main Methods:

• Ball milling and spray drying were employed for sample preparation.
• Powder X-ray diffraction, thermal analysis, infrared spectroscopy, Rietveld refinement, and dynamic vapor sorption were used for characterization.
• Kinetics and phase quantification were determined by Rietveld refinement.

Main Results:

• Ball milling partially amorphized LVXh, proceeding through an intermediate anhydrous form (LVXγ) to LVXam.
• A novel method for forming LVXγ and LVXam using mechanical forces was developed.
• Spray drying from water achieved complete LVXam formation, with a glass transition temperature of 80 °C.

Conclusions:

• LVXam formation is dependent on both the mechanism and the specific process used.
• Both ball milling and spray drying methods yielded LVXam with comparable stability, crystallizing to the hemihydrate form.
• This study enhances the understanding of fluoroquinolone solid-state transformations using sustainable manufacturing methods.