Abstract：
There have been significant advances in the formulation and stabilization of proteins in the liquid state over the past years since our previous review. Our mechanistic understanding of protein-excipient interactions has increased, allowing one to develop formulations in a more rational fashion. The field has moved towards more complex and challenging formulations, such as high concentration formulations to allow for subcutaneous administration and co-formulation. While much of the published work has focused on mAbs, the principles appear to apply to any therapeutic protein, although mAbs clearly have some distinctive features. In this review, we first discuss chemical degradation reactions. This is followed by a section on physical instability issues. Then, more specific topics are addressed: instability induced by interactions with interfaces, predictive methods for physical stability and interplay between chemical and physical instability. The final parts are devoted to discussions how all the above impacts (co-)formulation strategies, in particular for high protein concentration solutions.\'
摘要：
自我们先前的综述以来,在过去的几年中,在液态蛋白质的配制和稳定方面取得了重大进展。我们对蛋白质-赋形剂相互作用的机械理解有所增加，允许人们以更合理的方式开发配方。该领域已经走向更复杂和更具挑战性的配方，例如允许皮下给药的高浓度制剂和共同制剂。虽然大部分发表的作品都集中在单克隆抗体上，这些原则似乎适用于任何治疗性蛋白质，虽然单克隆抗体显然有一些鲜明的特点。在这次审查中,我们首先讨论化学降解反应。接下来是关于物理不稳定性问题的部分。然后，解决了更具体的主题：与接口交互引起的不稳定性，物理稳定性和化学和物理不稳定性相互作用的预测方法。最后部分致力于讨论上述所有因素如何影响(共同)制定战略，特别是对于高蛋白质浓度的溶液。\'
