Breakdown of isochronal superpositioning of 𝜶 - and 𝜷 - relaxation times in the van der Waals system - loratadine

In this paper, high-pressure (HP) dielectric studies on the van der Waals active pharmaceutical ingredient (API) - loratadine (LOR) were carried out. It was found that, surprisingly, the secondary (𝛽 ) relaxation, which, according to the Coupling Model (CM) predictions, was classified as a Johari-Goldstein (JG) process, separates from the structural (𝛼 )- mode with compression (although the shape of the 𝛼-peak is invariant to the thermodynamic conditions at constant 𝜏𝛼). Consequently, there is a breakdown of the isochronal superpositioning of 𝛼- and 𝛽 - relaxation times ( 𝜏𝛼 and 𝜏𝛽) in this system, which is a typical behavior for the secondary process with intermolecular character. Based on these findings, two possibilities concerning the origin of the -𝛽 relaxation in LOR have been proposed: 1) it is a non-JG process (probably originating from fluctuations within cyclic rings of the API molecule), which, however, satisfies the CM predictions; or 2) it is a JG-process, which similarly to a few earlier examined H-bonded compounds (e.g., probucol and sorbitol) is characterized by a different sensitivity to compression when compared to the 𝛼 - proces. Moreover, it was found that the activation entropy for the 𝛽 - process takes negative values, irrespective of the pressure conditions. That may be interpreted as due to conformational variation or the loss of translational and rotational degrees of freedom, leading to increased order in API due to densification. The results presented herein give a new insight into the relationship between the structural and secondary relaxations in the close vicinity of the glass transition temperature. Furthermore, they show that HP studies are crucial in elucidating the correlation between these processes.