A Study on the Characterization and Stability Implications of Investigating Local Mobility in Amorphous Pharmaceuticals

Abstract

There has been a deluge of research on the relationship between molecular mobility
and the physical and chemical stability of amorphous drugs in recent years. Glass transition and
global mobility-related molecular movements have been the primary targets of these investigations.
There were, however, a handful of cases where the volatility could not be explained by international
migration. The idea that b-relaxations, which occur at local scales well below the glass transition
temperature, may be impacting stability is gaining traction. One common method for determining
an amorphous pharmaceutical's mobility below the glass transition temperature (Tg) is to
extrapolate data collected above Tg. While not well-suited to pinpointing precise local mobility, this
kind of investigation may provide data about mobility in general. Our main goal from a
pharmacological standpoint is to prove that local movements are important in amorphous drugs,
especially in the Johari-Goldstein relaxations. In order to highlight the possible influence of local
mobility on the stability of amorphous phases, an assessment of the coupling model was carried out
that linked local movements with global mobility. We took into account the effects of water and
other additives when studying the local movements in an amorphous matrix present in molecular
dispersions. In conclusion, we have offered a concise review, highlighting the advantages and
disadvantages, of the most widely used instrumental methods for characterizing local movements.
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