ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States.
ReForm Biologics Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, United States.
J Pharm Sci. 2021 Nov;110(11):3594-3604. doi: 10.1016/j.xphs.2021.06.030. Epub 2021 Jun 26.
Many monoclonal antibody (mAb) solutions exhibit high viscosity at elevated concentrations, which prevents manufacturing and injecting of concentrated mAb drug products at the small volumes needed for subcutaneous (SC) administration. Addition of excipients that interrupt intermolecular interactions is a common approach to reduce viscosity of high concentration mAb formulations. However, in some cases widely used excipients can fail to lower viscosity. Here, using infliximab and ipilimumab as model proteins, we show that caffeine effectively lowers the viscosity of both mAb formulations, whereas other common viscosity-reducing excipients, sodium chloride and arginine, do not. Furthermore, stability studies under accelerated conditions show that caffeine has no impact on stability of lyophilized infliximab or liquid ipilimumab formulations. In addition, presence of caffeine in the formulations does not affect in vitro bioactivities of infliximab or ipilimumab. Results from this study suggest that caffeine could be a useful viscosity reducing agent that complements other traditional excipients and provides viscosity reduction to a wider range of mAb drug products.
许多单克隆抗体 (mAb) 溶液在高浓度下表现出高粘度，这使得难以在用于皮下 (SC) 给药的小体积下制造和注射高浓度 mAb 药物产品。添加中断分子间相互作用的赋形剂是降低高浓度 mAb 制剂粘度的常用方法。然而，在某些情况下，广泛使用的赋形剂可能无法降低粘度。在这里，我们使用英夫利昔单抗和伊匹单抗作为模型蛋白，表明咖啡因可有效降低这两种 mAb 制剂的粘度，而其他常用的降低粘度赋形剂氯化钠和精氨酸则不能。此外，加速条件下的稳定性研究表明，咖啡因对冻干英夫利昔单抗或液体伊匹单抗制剂的稳定性没有影响。此外，赋形剂中咖啡因的存在不会影响英夫利昔单抗或伊匹单抗的体外生物活性。这项研究的结果表明，咖啡因可能是一种有用的粘度降低剂，可补充其他传统赋形剂，并为更广泛的 mAb 药物产品提供粘度降低效果。
