Solid-state properties of Nifurtimox. Preparation, analytical characterization, and stability of an amorphous phase

MORONI, A. B.; PEREZ MAYORAL, E.; LIONELLO, D. F.; VEGA, D. R.; KAUFMAN, T. S.; CALVO, N. L.

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2023 vol. 184 p. 25 - 35

0939-6411

Nifurtimox (NFX) is a nitrofuran derivative used to treat Chagas disease, a neglected disease caused by theprotozoan Trypanosoma cruzi. The drug is very sparingly soluble in aqueous media and no other solid phases ofNFX have been reported to date.The preparation of the amorphous mode of NFX is reported, as well as its characterization by hot stage microscopy,thermal (differential scanning calorimetry and thermogravimetric analysis), spectroscopic (solid statenuclear magnetic resonance, mid-infrared, and near-infrared), diffractometric and functional (powder dissolutionrate) means.The stability of the new phase was investigated. This was characterized using thermal, spectroscopic, anddiffractometric methods, finding out its spontaneous reversion to the crystalline state, as sign of instability. Inaddition, the amorphous material proved to be sensitive to temperature, pressure, and mechanical stress, all ofwhich accelerated phase conversion. However, it was able to remain stable in a model polymeric amorphoussolid dispersion with PEG 4000 for more than one month. An approach for monitoring the conversion of theamorphous phase to its crystalline counterpart under thermal stress by chemometric analysis of mid-infraredspectra at different temperatures is also disclosed.