National Institute of Health Sciences, Kawasaki, Kanagawa, Japan.
Adv Exp Med Biol. 2018;1081:371-383. doi: 10.1007/978-981-13-1244-1_20.
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.
冷冻干燥是一种常用于制备含有结构复杂的活性成分和药物传递系统载体的药物制剂的方法。在较低温度下进行的固化显著提高了蛋白质、肽、抗生素、疫苗和脂质体的储存稳定性，这些物质在水溶液中稳定性较差。然而，冷冻干燥过程的各个环节（冷冻、初级干燥、二级干燥）都会使蛋白质受到各种压力。某些赋形剂，包括二糖（如蔗糖、海藻糖）和氨基酸，可以添加到配方中，通过取代水分子提供的分子相互作用来保护蛋白质和超分子药物传递系统免受与冷冻和储存相关的物理压力。一些赋形剂将活性成分嵌入具有低分子流动性的玻璃态固体中，从而降低化学反应性。因此，在冷冻干燥过程中使用适当的赋形剂和工艺控制对于保护蛋白质非常重要。本章介绍了冷冻干燥在药物生产过程中的应用，主要侧重于蛋白质治疗药物的配方和工艺优化。
