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 ( T β ) in both amorphous celecoxib and various celecoxib amorphous solid dispersions [Be̅rziņš, K. Mol. Pharmaceutics 2021, 18(10), 3882-3893]. In this study, we further investigated the application of this technique to determine T β , 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 ( T γ ). 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.