The effective use of differential scanning calorimetry in the optimisation of freeze-drying processes and formulations.

The formulation and processing variables required for the effective freeze-drying of labile biologicals can be determined from an understanding of the physics of freeze-concentration. Three measurable values, Tg' (the glass temperature associated with maximum freeze-concentration), Wg' (the unfrozen water at this temperature) and Tg (the glass temperature of the dried product) are the keystones. These can be obtained by differential scanning calorimetry. This paper describes their measurement. Techniques to increase the detectability of glass transitions are discussed. Method of calculating Wg' from DSC power-time curves are critically reviewed. An example is presented in which it is demonstrated how failure to perform primary drying below the glass transition results in products on inferior quality. Finally, it is described how measurements of the glass temperature of the "dry" product can be used to predict storage stability. The limitation of using moisture determination to predict stability is high-lighted.