Lyophilization of biotechnology products.

In this review the lyophilization of biotechnology products is discussed. It is emphasized that the final quality of a protein product is determined by an interplay between the proper choice of excipients and the freeze-drying process. A crystalline matrix after freeze-drying is detrimental for the protein product. A glassy amorphous state is a prerequisite for stability, however a glassy state as such will not assure sufficient stability. The glass temperature which defines the state of the freeze-dried cake can be influenced by the moisture content and the choice of excipients.

Evaluation of the physical stability of freeze-dried sucrose-containing formulations by differential scanning calorimetry.

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, Tg, of the amorphous cake, crystallization, and melting of sucrose are observed with DSC. Tg appeared to be an important characteristic of the physical stability of the amorphous freeze-dried cake. A storage temperature above Tg results in collapse or shrinkage of the cake, which for a sucrose-based formulation, may be accompanied by crystallization of the sucrose. The Tg of the amorphous sucrose is influenced by other components present in the cake. Dextran-40 raised Tg, while the addition of glycine to the formulation lowered Tg. The residual moisture content strongly influences Tg, since water acts as a plasticizer of the system; the higher the moisture content, the lower the Tg 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.