Biopharma Process Systems Ltd, Winchester, UK.
National Institute for Biological Standards and Control (NIBSC), Potters Bar, UK.
Methods Mol Biol. 2021;2180:99-127. doi: 10.1007/978-1-0716-0783-1_3.
Freeze-drying is a complex process despite the relatively small number of steps involved, since the freezing, sublimation, desorption, and reconstitution processes all play a part in determining the success or otherwise of the final product qualities, and each stage can impose different stresses on a product. This is particularly the case with many fragile biological samples, which require great care in the selection of formulation additives such as protective agents and other stabilizers. Despite this, the process is widely used, not least because once any such processing stresses can be overcome, the result is typically a significantly more stable product than was the case with the starting material. Indeed, lyophilization may be considered a gentler method than conventional air-drying methods, which tend to apply heat to the product rather than starting by removing heat as is the case here. Additionally, due to the high surface area to volume ratio, freeze-dried materials tend to be drier than their conventionally dried counterparts and also rehydrate more rapidly. This chapter provides an overview of freeze-drying (lyophilization) of biological specimens with particular reference to the importance of formulation development, characterization, and cycle development factors necessary for the commercial exploitation of freeze-dried products, and reviews the recent developments in analytical methods which have come to underpin modern freeze-drying practice.
冷冻干燥是一个复杂的过程，尽管涉及的步骤相对较少，但由于冷冻、升华、解吸和再形成过程都对最终产品质量的成败起着决定性作用，而且每个阶段都可能对产品施加不同的压力。对于许多脆弱的生物样本来说尤其如此，它们在选择配方添加剂（如保护剂和其他稳定剂）时需要非常小心。尽管如此，该工艺还是被广泛应用，尤其是因为一旦克服了任何此类加工压力，最终产品通常会比初始材料更加稳定。事实上，与传统的风干方法相比，冻干可以被认为是一种更温和的方法，因为传统的风干方法往往会对产品加热，而不是像这里那样先去除热量。此外，由于高的表面积与体积比，冻干的材料往往比传统干燥的材料更干燥，并且复水速度更快。本章概述了生物样本的冷冻干燥（冻干），特别提到了配方开发、特性和商业化开发冻干产品所需的循环开发因素的重要性，并回顾了最近在分析方法方面的发展，这些发展为现代冷冻干燥实践提供了支持。
