How does pressure affect the molecular dynamics, intramolecular interactions, and the relationship between structural (α) and secondary (JG-β) relaxation above and below the glass transition temperature in binary mixtures of H-bonded API - probucol and acetylated saccharides?

In this paper, the molecular dynamics as well as inter- and intramolecular interactions in the homogenous solid dispersions (SDs) of active pharmaceutical ingredient - probucol (PRO) with acetylated glucose (acGLU), acetylated sucrose (acSUC), and sucrose acetoisobutyrate (aibSUC), prepared in 5:1 molar ratio, have been investigated using broadband dielectric (BD) and Fourier transform infrared (FTIR) spectroscopy. Importantly, high pressure dielectric measurements revealed that as for neat PRO, a breakdown of the isochronal structural (α) and JG-β exact superpositioning, due to increasing separation between both processes under compression, can also be detected in its mixtures with acetylated saccharides (acSACCHs). Furthermore, the analysis of temperature dependences of JG-β-relaxation times for PRO and PRO-acSACCH SDs at selected isobaric conditions indicated the increase in the cooperativity of the secondary process (reflected in the value of the activation entropy, ΔS) at elevated pressure in all systems. The mere addition of the small amount of excipient to neat PRO (p = 0.1 MPa) resulted in a greater value of ΔS (it was the most noticeable in the case of aibSUC). Further FTIR studies carried out on the pressure densified glasses of PRO, and binary mixtures suggested that the observed changes in the cooperativity of the JG-β-process, as well as the failure of the exact isochronal superpositioning of α- and JG-β relaxation times, are due to varying H-bond pattern in the examined single- and two-component systems at high compression/in the presence of saccharide.