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The physical and chemical instability of amorphous pharmaceuticals during storage has become a major problem for the pharmaceutical industry, as most of the pharmaceuticals including some life saving drugs are also found to be poorly water soluble. Molecular mobility is a key factor to understand the various crucial parameters that determine the stability of amorphous phase. The molecular dynamics in the supercooled liquid and glassy states of three Active Pharmaceutical Ingredients (API) Acemetacin, Brucine and Colchicine were characterized by molecular relaxation (mobility) using broadband dielectric spectroscopy (BDS) in a wide frequency range. Primary structural relaxation and intra-molecular (non Johari-Goldstein) secondary relaxation were observed above and below Tg respectively in all three title compounds. The dielectric spectra were fitted to the Havriliak-Negami (HN) function. The temperature dependence of the structural relaxation time followed Vogel-Fulcher-Tamman (VFT) equation and the secondary relaxation followed Arrhenius equation. By Coupling model (CM) prediction, the secondary relaxations in all title compounds were found to be non JG. The width of the structural relaxation peak decreases with temperature for brucine and colchicine while it increases for acemetacin. By Differential Scanning Calorimetry (DSC) experiment, we confirmed that the selelcted compounds are good glass formers and their structural properties and hydrogen bonding were studied by Fourier Transform Infrared spectroscopy (FTIR) and verified by Density Functional theory (DFT). By BDS, the parameters which describe the molecular dynamics in the supercooled and glassy states of the title compounds, like glass transition temperature (Tg) the width of the α relaxation (βKWW), the temperature dependence of α-relaxation times (τα), the fragility (m) and the activation energy of the secondary relaxation (Ea-γ), were determined. The higher values of Tg determined (307.9 K for acemetacin, 366.2 K for brucine and 374.5 K for colchicine) indicates stability of their amorphous phase at normal storage conditions. The fragility index values of the title compounds indicate intermediately fragile behaviour. The FTIR analysis of the crystalline and amorphous states of brucine, acemetacin and colchicine shows the presence of hydrogen bonding in amorphous phase of the title compounds and verified that their molecular structures were retained in the amorphous state.

Nowadays the study of physiochemical stability of amorphous pharmaceuticals is of great interest in the field of medicinal application due to its enhanced water solubility and bioavailability than its crystalline counterpart. Molecular relaxations play an important role in understanding the physical stability of amorphous drugs. Hence herein, we investigated the molecular dynamics of three pharmaceutically important drugs, namely clofoctol, droperidol and probucol by means of broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC). The dielectric spectra in the supercooled state were fitted by Havriliak-Negami (HN) function, while in the glassy state with Cole-Cole equation. The structural relaxation followed non-Arrhenius temperature dependence and followed time-honored Vogel-Fulcher-Tamman (VFT) equation and the secondary relaxation followed Arrhenius equation. The Coupling model (CM) prediction was used to find the origin of the secondary relaxations. Although the three drugs were found to be fragile, clofoctol and droperidol showed recrystallization tendency. It was amazing that the three samples showed a good correlation between the stretch exponent βKWW and the dielectric strength Δe(Tg). In addition, the molecular simulation was used to verify the presence of non-JG (Johari-Goldstein) secondary relaxation due to side chain rotation.

In this paper, thermal and spectroscopic investigations on a room temperature ionic liquid, 1-Butyl-1-methyl pyrrolidinium bis(trifluoromethylsulfonyl)imide ([BMPyr][TFSI]) were carried out using differential scanning calorimetry and broadband dielectric spectroscopy over wide temperature to study the molecular mobility, charge transport properties, and conductivity relaxation. The quantum mechanical calculations were used to study its polar nature. The isochronal cooling and heating were measured to get an estimation of the glass transition temperature. The study revealed that [BMPyr][TFSI] is an intermediate fragile system with a fragility index of 96.3 and Tg around 182 K. A strong translational–rotation coupling of the [BMPyr][TFSI] molecules were observed in the glassy state due to intermolecular Johari Goldstein relaxation. It showed an excellent agreement with the coupling model predictions. The conductivity behavior of [BMPyr][TFSI] follows Johncher's power law, and its temperature dependence well fits with the Arrhenius equation having an activation energy of 686.3 kJ/mol. The glass transition temperature obtained from DSC, isochronal cooling data and heating data were in good agreement.