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In this paper, thermal properties, atomic-scale structure, and molecular dynamics (at ambient and high pressure) of native melatonin (MLT) and its partially-deuterated derivative (MLT-d2) have been investigated. Based on infrared spectroscopy, it was shown that treating MLT with D2O causes the replacement of hydrogen atoms attached to the nitrogen by deuterium. The degree of such substitution was very high (> 99%) and the deuterated sample remained stable after exposure to the air as well as during the melting and vitrification processes. Further calorimetric studies revealed the appearance of a peculiar thermal event before the melting of crystalline MLT-d2, which was assigned by the X-ray diffraction to a local negative thermal expansion of the unit cell. Finally, the high-pressure dielectric experiments indicated a few interesting findings, including the variation in the shape of the structural relaxation peak during compression, the difference in the pressure evolution of the glass transition temperature, and the temperature dependence of activation volume for both MLT species. The variations in these parameters manifest a different impact of the compression/densification on the dynamics of hydrogen and deuterium bonds in the native and partially-deuterated MLT, respectively. [ABSTRACT FROM AUTHOR]

In this paper, thermal and structural properties, as well as molecular dynamics of co-amorphous binary mixtures composed of itraconazole (ITZ) and four other active pharmaceutical ingredients (APIs) with antifungal activity (posaconazole (POS), ketoconazole (KET), fluconazole (FLU), and voriconazole (VOR)), have been investigated. Calorimetric measurements indicated that with increasing concentration of each excipient (EXC), the glass transition temperature and phase transition temperatures, related to the formation of nematic and smectic order, are affected in the binary systems. Comprehensive analysis of the enthalpy of isotropic-nematic transition and the temperature dependence of the order parameter, calculated from infrared data for selected mixtures, supported by the results of X-ray diffraction , enabled us to confirm the suppression of liquid crystalline (LC) ordering in ITZ by KET, FLU, and VOR. On the other hand, ITZ enforced the nematic-like molecular arrangement of POS. Further dielectric measurements revealed that the type of EXC and its content in the mixture have no impact on the ratio of α - and δ -relaxation times (τ α and τ δ , respectively) in ITZ. Moreover, it was shown that δ -process is more sensitive to the isotropic-nematic phase transition than the α -one, and the formation of the nematic phase in this API occurs at different τ α and τ δ , dependently on the type of EXC and its concentration in the mixture. Summarizing, the results of our studies are much different with respect to those reported previously by Kozyra et al. [Mol. Pharm. 15 (2018) 5192–5206] and by some of us [Kaminska et al. Eur. J. Pharm. Biopharm. 88 (2014) 1094–1104] for ITZ mixed with various polymers and acetylated maltose, respectively. This finding clearly indicates that there is a different impact of the low and high molecular weight excipients on the ability in the formation of LC phases in ITZ, which may have important implications for the further development of the formulations of this pharmaceutical. Unlabelled Image • The degree of spatial arrangement of ITZ molecules is affected in binary systems. • The smectic ordering in ITZ is being suppressed by POS, KET, FLU and VOR. • In the ITZ-POS binary mixture, ITZ enforces the molecular (nematic) order of POS. • Results of our studies are in contrast to those reported for ITZ-polymer systems. [ABSTRACT FROM AUTHOR]