Evaluation of the Physical Stability of Freeze-Dried Sucrose-Containing Formulations by Differential Scanning Calorimetry

Abstract

Freeze-dried samples of sucrose with buffer salts, amino acids, or dextran have been analyzed with differential scanning calorimetry (DSC) to evaluate the use of DSC thermograms in predicting the physical storage stability. The glass transition temperature, T_g, of the amorphous cake, crystallization, and melting of sucrose are observed with DSC. T_g appeared to be an important characteristic of the physical stability of the amorphous freeze-dried cake. A storage temperature above T_g results in collapse or shrinkage of the cake, which for a sucrose-based formulation, may be accompanied by crystallization of the sucrose. The T_g of the amorphous sucrose is influenced by other components present in the cake. Dextran-40 raised T_g, while the addition of glycine to the formulation lowered T_g. The residual moisture content strongly influences T_g, since water acts as a plasticizer of the system; the higher the moisture content, the lower the T_g and the less physically stable the freeze-dried cake. Crystallization of amorphous sucrose is shown to be inhibited by high molecular weight components or ionic compounds. DSC analysis of freeze-dried cakes proved to be a powerful tool in formulation studies.