Arecor Limited, 2 Cambridge Science Park, Cambridge, CB4 0FE, UK.
Adv Drug Deliv Rev. 2011 Oct;63(13):1107-17. doi: 10.1016/j.addr.2011.09.008.
The use of monoclonal antibodies as therapeutic agents has been increasing steadily over the last decade for the treatment of various conditions. There is often a need to deliver a large dose of the protein, so there is a trend toward developing commercially viable liquid formulations of highly concentrated antibodies. Such concentrated solutions are associated with a number of challenges, including optimization of production processes, plus chemical and physical stability of the final product where solution viscosity becomes a critical quality attribute. Assessment of the rheological characteristics of concentrated compositions is essential as are development strategies to reduce the viscosity. This review covers the state-of-the-art rheology measurement techniques, focusing particularly on concentrated protein solutions. Current understanding of the mechanisms leading to high viscosity and control by formulation parameters is discussed.
过去十年中，单克隆抗体作为治疗药物的应用稳步增加，可用于治疗各种病症。通常需要给予大剂量的蛋白质，因此开发高浓度抗体的商业可行的液态制剂是一种趋势。此类浓缩溶液存在许多挑战，包括优化生产工艺，以及最终产品的化学和物理稳定性，其中溶液黏度成为关键质量属性。评估浓缩制剂的流变特性至关重要，还需要制定降低黏度的策略。本文综述了最新的流变测量技术，特别关注了浓缩蛋白溶液。文中讨论了导致高黏度的机制以及通过配方参数进行控制的当前认识。
