Work

Impact of temperature and solvent vapors on the stability and phase transitions of amorphous vilanterol trifenatate obtained by vitrification and cryomilling

Year: 2025

Type: article

Abstract: In this paper, the effect of temperature, as well as water and ethanol vapour, on the phase transitions and physicochemical stability of amorphous vilanterol trifenatate (VIT) obtained through vitrification and cryomilling, was investigated. We found that the freshly prepared samples are fully amorphous and maintain physical stability even after 6 months of storage at room temperature. Dynamic vapour sorption (DVS) measurements of the crystalline VIT revealed that this active substance can be classified as slightly hygroscopic. The same experiments carried out on both amorphous systems after vapour sorption of water (at T = 298 and 313 K), and ethanol (at T = 298 K) revealed significant differences between them (and the crystalline VIT). Detailed calorimetric and structural studies showed that the vitrified VIT remains stable upon exposure to water vapour at T = 298 K and 313 K, while the cryomilled substance is no longer amorphous. In turn, after ethanol sorption at T = 298 K, both vitrified and cryomilled samples crystallized. The former system returned to its basic polymorphic form I, while the cryomilled one formed a different solid state phase (resembling a polymorph XII described in the literature). Moreover, additional temperature-dependent X-ray diffraction studies indicated some small polymorphic transformations occurring during heating of VIT after water- and ethanol-assisted DVS experiments. Our studies show that exposing amorphous samples obtained through different methods to an atmosphere with a high content of water or ethanol vapour can significantly alter the physical stability of the disordered substances and may lead to the formation of different polymorphs. These results are rare in the current literature and offer novel insights. Furthermore, given the increasing interest in amorphous drugs within the pharmaceutical industry, these results may have important implications for the preparation and storage of formulations containing active pharmaceutical ingredients in the amorphous state.

Source: Journal of Molecular Liquids

DOI: 10.1016/j.molliq.2025.128245