Thermal Behavior and Slow Relaxation Dynamics in Amorphous Efavirenz: A Study by DSC, XRPD, TSDC, and DRS

Abstract

The analysis of the thermal behavior of efavirenz showed a high glass-forming ability and good glass stability of this glass-forming liquid at room temperature. No polymorphic forms were formed either by cold crystallization or by recrystallization from solvent acetone. The determination of the dynamic fragility by the differential scanning calorimetry, thermally stimulated depolarization currents (TSDC), and dielectric relaxation spectroscopy (DRS) techniques is unanimous in suggesting efavirenz as a moderately fragile liquid. With DRS, secondary relaxations were detected, however, with weak intensities that did not allow the respective kinetic analysis; in contrast, TSDC allows clearly resolving the components of the secondary β-relaxation below Tg, with activation energies distributed between about 75 and 90 kJ mol−1 and Arrhenius prefactors of the order of 10−13 s. In this regard, the TSDC technique proved to be more effective compared to DRS in characterizing the secondary relaxation. The glass forming ability and glass stability found for efavirenz have been discussed in terms of various thermodynamic and kinetic parameters such as the reduced glass transition temperature, Tgred, the dynamic fragility, m, the stretching exponent, βKWW, the melting entropy, ΔSfus, and the molecular stiffness. The exceptionally low value of efavirenz fusion entropy was highlighted as a key feature of the thermal behavior of this glass-forming liquid.