Résumé
Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone
drug
that exists in both hydrated and anhydrous/dehydrated forms. Due to
the complexity of such a compound, the primary aim of this study was
to investigate the amorphization capabilities and solid-state transformations
of LVXh when exposed to mechanical treatment using ball milling. Spray
drying was utilized as a comparative method for investigating the
capabilities of complete LVX amorphous (LVXam) formation. The solid
states of the samples produced were comprehensively characterized
by powder X-ray diffraction, thermal analysis, infrared spectroscopy,
Rietveld method, and dynamic vapor sorption. The kinetics of the process
and the quantification of phases at different time points were conducted
by Rietveld refinement. The impact of the different mills, milling
conditions, and parameters on the composition of the resulting powders
was examined. A kinetic investigation of samples produced using both
mills disclosed that it was in fact possible to partially amorphize
LVXh upon mechanical treatment. It was discovered that LVXh first
transformed to the anhydrous/dehydrated form γ (LVXγ),
as an intermediate phase, before converting to LVXam. The mechanism
of LVXam formation by ball milling was successfully revealed, and
a new method of forming LVXγ and LVXam by mechanical forces
was developed. Spray drying from water depicted that complete amorphization
of LVXh was possible. The amorphous form of LVX had a glass transition
temperature of 80 °C. The comparison of methods highlighted that
the formation of LVXam is thus both mechanism- and process-dependent.
Dynamic vapor sorption studies of both LVXam samples showed comparable
stability properties and crystallized to the most stable hemihydrate
form upon analysis. In summary, this work contributed to the detailed
understanding of solid-state transformations of essential fluoroquinolones
while employing greener and more sustainable manufacturing methods.