Dielectric Relaxation Study at Ambient and Elevated Pressure of the Modeled Lipophilic Drug Fenofibrate.

Abstract

We have investigated the molecular dynamics in supercooled liquid and glassy state of the pharmaceutical agent fenofibrate. To do that, dielectric relaxation studies at ambient and elevated pressure were performed. Data collected at atmospheric pressure were found to be in good agreement with that already reported in the literature. High-pressure studies enable us to distinguish the secondary relaxation processes of the different molecular origin. This includes (i) pressure insensitive γ-relaxation of the activation energy Ea = 28 kJ/mol and (ii) β-relaxation that senses the density increase and originates most probably from the intermolecular movements (Ea = 77 kJ/mol at 480 MPa). The results of high-pressure studies have also revealed the validity of isochronal superposition and decoupling between α-relaxation and translational motions of charged species reflected by dc conductivity. The latter one was found to intensify with increasing pressure. Finally, we also show that the presence of quite complex inter- and intramolecular hydrogen bonds might still exert some subtle effect on the molecular dynamics of supercooled fenofibrate.