F. Hoffmann-La Roche Ltd., Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, Grenzacherstrasse 124, 4070 Basel, Switzerland; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
F. Hoffmann-La Roche Ltd., Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, Grenzacherstrasse 124, 4070 Basel, Switzerland.
J Pharm Sci. 2020 Aug;109(8):2393-2404. doi: 10.1016/j.xphs.2020.03.010. Epub 2020 Mar 16.
Surfactants play an important role in stabilizing proteins in liquid formulations against aggregate/particle formation during processing, handling, storage, and transportation. Only 3 surfactants are currently used in marketed therapeutic protein formulations: polysorbate 20, polysorbate 80, and poloxamer 188. While polysorbates are the most widely used surfactants, their intrinsic oxidative and hydrolytic degradation issues highlights the importance of alternative surfactants such as poloxamer 188. Here, we compare polysorbates and poloxamer 188 with regards to their stabilizing properties under various stress and storage conditions for several monoclonal antibody formulations. Our data shows that poloxamer 188 can provide suitable protection of monoclonal antibodies against interfacial stress in liquid formulations in vials. However, visible protein-polydimethylsiloxane (PDMS; silicone oil) particles were observed in vials after long-term storage at 2-8°C for some protein formulations using poloxamer 188, which were not observed in polysorbate formulations. The occurrence of these protein-PDMS particles in poloxamer 188 formulations is a protein-specific phenomenon that may correlate with protein physico-chemical properties. In this study, the primary source of the PDMS in particles found in vials was considered to be from the primary packaging stoppers used. Our findings highlight benefits, but also risks associated with using poloxamer 188 in liquid biotherapeutic formulations.
表面活性剂在稳定液体制剂中的蛋白质方面发挥着重要作用，可防止在加工、处理、储存和运输过程中形成聚集体/颗粒。目前，只有 3 种表面活性剂用于市售治疗性蛋白制剂：吐温 20、吐温 80 和泊洛沙姆 188。虽然聚山梨酯是使用最广泛的表面活性剂，但它们固有的氧化和水解降解问题突出了替代表面活性剂（如泊洛沙姆 188）的重要性。在这里，我们比较了吐温 20 和泊洛沙姆 188 在几种单克隆抗体制剂的各种应激和储存条件下的稳定特性。我们的数据表明，泊洛沙姆 188 可以为单克隆抗体在小瓶中的液体制剂中提供界面应激的适当保护。然而，在某些蛋白制剂中，在 2-8°C 下长期储存后，在小瓶中观察到可见的蛋白-聚二甲基硅氧烷（PDMS；硅油）颗粒，而在吐温制剂中未观察到这些颗粒。泊洛沙姆 188 制剂中这些蛋白-PDMS 颗粒的出现是一种蛋白特异性现象，可能与蛋白物理化学性质相关。在这项研究中，认为小瓶中颗粒中 PDMS 的主要来源是所用的初级包装瓶塞。我们的研究结果强调了在液体生物治疗制剂中使用泊洛沙姆 188 的益处，但也存在风险。
