Dielectric spectroscopic studies in supercooled liquid and glassy states of Acemetacin, Brucine and Colchicine

Abstract 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 T g 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 (T g ) the width of the α relaxation (β KWW ), the temperature dependence of α-relaxation times (τ α ), the fragility (m) and the activation energy of the secondary relaxation (E a-γ ), were determined. The higher values of T g 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.