Freeze-drying is a popular method to prepare pharmaceutical formulations containing structurally complex active ingredients and drug delivery system carriers. The solidification performed at lower temperature significantly improves storage stability of proteins, peptides, antibiotics, vaccines, and liposomes, which are marginally stable in aqueous solutions. Individual components of the freeze-drying process (freezing, primary drying, secondary drying), however, expose proteins to various stresses. Certain excipients, including disaccharides (e.g., sucrose, trehalose) and amino acids, can be added to protect the proteins and supramolecular drug delivery systems against physical stress associated with freezing and storage by substituting the molecular interactions provided by water molecules. Some excipients embed the active ingredients in glass-state solids with low molecular mobility, thereby reducing chemical reactivity. Thus, the use of appropriate excipients and process control is important to protect proteins during freeze-drying. This chapter describes the applications of freeze-drying in the pharmaceutical production process, mainly focusing on formulation and process optimization for protein therapeutics.
Keywords: Excipient; Freeze-drying; Pharmaceutical formulations; Protein; Stabilization.