ABSTRACT
Hydration Limit and Long-Term Stability..................................................... 303
Hydration Limit of Small Molecule Hydrophilic Glasses .......................... 304
Hydration Limit of Hydrophilic Polymer Glasses....................................... 306
Hydration Limit of Protein Glasses ................................................................ 307
Is the Hydration Limit Related to the Zero Mobility Temperature?......... 307
References ........................................................................................................... 307
Predicting the long-term stability of amorphous solids remains an
unresolved challenge. The simplest approach, selecting a storage condition
well below the glass-transition temperature, T
, has been widely used. More
recently, determination of the so-called zero mobility temperature, T
, the
temperature at which the characteristic relaxation time exceeds pharmaceu-
tically relevant storage times, is a frequently used predictor of the physical
and chemical stability of amorphous pharmaceutical solids. The effect of
residual water on stability is often estimated using the T
of the hydrated
amorphous solid, as dictated by its degree of plasticization by water.
With the advent of automated water vapor sorption microbalances, rapid
measurements of the moisture sorption isotherms of amorphous systems
have become commonplace. Despite these advances, the combined effects
of water content and storage temperature, T
