Vaccine Formulation Development, MedImmune, 319 Bernardo Ave, Mountain View, CA 94043, USA.
Curr Pharm Biotechnol. 2012 Mar;13(3):471-96. doi: 10.2174/138920112799361990.
Freeze drying, or lyophilization is widely used for biopharmaceuticals to improve the long term storage stability of labile molecules. This review examines general theory and practice of rational lyophilization of biopharmaceuticals. Formulation development involving the selection of appropriate excipients, their associated physical properties, and mechanism of action in achieving a stable drug product are primary considerations for a successful lyophilization program. There are several parameters considered critical on the basis of their relationship to lyophilization cycle development and protein product stability. This along with the importance of analytical methods to provide insight toward understanding properties of drug product stability and cake structure are discussed. Also, aspects of instability found in lyophilized biopharmaceutical products, their degradation pathways and control are elucidated. Finally, container-closure requirements and drug product handling are described in context of the caveats to avoid compromising drug product quality.
冷冻干燥，又称冻干，广泛应用于生物制药领域，以提高不稳定分子的长期储存稳定性。本文综述了生物制药合理冻干的一般理论和实践。制剂开发涉及选择合适的赋形剂，及其在实现稳定药物产品方面的相关物理性质和作用机制，是成功冻干方案的主要考虑因素。有几个参数被认为是关键的，因为它们与冻干周期开发和蛋白质产品稳定性有关。本文还讨论了分析方法的重要性，以提供对理解药物产品稳定性和饼状物结构特性的洞察力。此外，还阐述了冻干生物制药产品中发现的不稳定性、其降解途径和控制方面的问题。最后，描述了容器-密封要求和药物产品处理，以避免损害药物产品质量的注意事项。
