Breakdown of the isochronal structural (α) and secondary (JG β) exact superpositioning in probucol - A low molecular weight pharmaceutical

Abstract

In this paper, Broadband Dielectric Spectroscopy (BDS) has been applied to study the molecular dynamics of the two active pharmaceutical ingredients (APIs), probucol (PRO) and droperidol (DRO), above and below the glass transition temperature, at varying thermodynamic conditions. We found that the structural (α)-relaxation process in both compounds is sensitive to compression. It was reflected in the high pressure coefficients of the glass transition temperature, dTg/dp = 227 K/GPa and dTg/dp = 427 K/GPa for DRO and PRO, respectively. In this context, it is worthwhile to emphasize that dTg/dp calculated for the latter API is the highest reported to date for the low molecular weight glass formers. Furthermore, the data collected upon squeezing samples revealed that the pressure dependence of the relaxation times of the Johari Goldstein (JG) β-process in PRO is weaker with respect to that of structural relaxation. Thus, a breakdown of exact superposition of both modes has been noted. A slightly different scenario was observed in DRO, where relaxation times of the secondary non-JG γ-process, obtained at different T and p, plotted versus Tg/T, collapsed forming a single curve. A breakdown of exact isochronal superpositioning of α- and JG β-relaxation times at varying thermodynamic conditions in PRO, that is weakly H-bonded low molecular weight glass former, is in accordance with the data reported for the strongly associating compounds (e.g., sorbitol). Moreover, recently a similar scenario has been observed for some polymers, i.e., 1,4-polybutadiene (PBD) (Ransom et al., 2018), poly(methyl methacrylate) (PMMA) (Casalini and Roland, 2013) and polyisoprene (PI) (Kołodziej et al., 2018). This phenomenon, which is consistent with the approximate invariance of the ratio of these two relaxation times to change of thermodynamics conditions (as predicted by the Coupling Model), was assigned to the increasing torsional rigidity of the macromolecule backbone or alternatively to the non-uniform responses to variations of temperature and pressure of the distributed modes composing the JG β-process, resulting in changes of the spectral shape and different fβ(p,T) obtained from the fitting procedure. One can suppose that due to the variation in the population of weak H-bonds at elevated pressure in PRO, the latter effect might be enhanced, contributing to the observed experimental finding. Finally, the data reported herein emphasize the impact of molecular aspects related to specific interactions on the correlation between α- and JG β-relaxation at varying T and p conditions.