The Effect of Annealing on the Stability of Amorphous Solids: Chemical Stability of Freeze-Dried Moxalactam

The Impact of Thermal Treatment on the Stability of Freeze Dried Amorphous Pharmaceuticals: I. Dimer Formation in Sodium Ethacrynate

“…The improved stability is believed to the result of “extra” physical aging achieved through using a higher secondary drying temperature. Recently, this system has been investigated in more detail, using various postlyophilization annealing methods, and again, small increases in the chemical stability upon aging at various temperatures below T g were observed,24 thereby confirming the earlier studies 23. There is also a report of an annealing effect in the area of food chemistry, where the Maillard reaction rate is reduced by about 20% after aging the glassy formulation for 3 weeks at 50°C 25.…”

Mechanisms of protein stabilization in the solid state

“…Consequently, the stability of the product can be improved if mobility and instability are coupled in the system. 85 If the enthalpy versus temperature curve above T g were to continue to lower temperatures, the super-cooled liquid would attain lower enthalpy than the crystalline state at the Kauzmann temperature (T K ) (Fig. 6).…”

“…There is not a single glassy state; the thermodynamic (and dynamic) properties of a glass depend on how it was formed and its thermal history post formation. [85][86][87] For example, annealing, or heating an amorphous sample below its T g for a period of time, can reduce the molecular mobility below T g . Consequently, the stability of the product can be improved if mobility and instability are coupled in the system.…”

The Effect of Bulking Agents on the Chemical Stability of Acid-Sensitive Compounds in Freeze-Dried Formulations: Sucrose Inversion Study

“…11 The rate constant decreases with an increase in the value of Hammett acidity function (i.e., with a decrease in the apparent solid-state acidity), as could be expected for an acid-catalyzed reaction. Indeed, it has been shown that the processing history (e.g., annealing) may have a significant impact on the rate of both chemical 25 and physical processes 26 in freeze-dried and other amorphous materials. This scatter might be an indication that the Hammett acidity function is not the only determinant of the chemical reactivity of amorphous lyophiles, even in the case of a relatively simple reaction process, such as sucrose inversion.…”