Low-Frequency Raman Spectroscopy as an Avenue to Determine the Transition Temperature of β- and γ-Relaxation in Pharmaceutical Glasses

In an earlier investigation, low-frequency Raman (LFR) spectroscopy was shown to detect the transition temperature of the β-relaxation (Tβ) in both amorphous celecoxib and various celecoxib amorphous solid dispersions [ Bē rziņš, K. et al. Mol. Pharmaceutics 2021, 18(10), 3882-3893 ]. In this study, we further investigated the application of this technique to determine Tβ, an important parameter for estimating crystallization potency of amorphous drugs. Alongside commercially available amorphous drugs (zafirlukast and valsartan disodium salt), differently melt-quenched samples of cimetidine were also analyzed. Overall, the variable-temperature LFR measurements allowed for an easy access to the desired information, including the even lesser transition of the tertiary relaxation motions (Tγ). Thus, the obtained results not only highlighted the sensitivity, but also the practical usefulness of this technique to elucidate (subtle) changes in molecular dynamics within amorphous pharmaceutical systems.