Buffer Capacity of Biologics-From Buffer Salts to Buffering by Antibodies
Buffer Capacity of Biologics-From Buffer Salts to Buffering by Antibodies
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DOI：
10.1002/btpr.1682
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Garidel, Patrick
中科院分区：
文献类型：
--
作者：
Karow, Anne R.;Bahrenburg, Sven;Garidel, Patrick
控制pH值对于各种生物制药工艺步骤至关重要。生物制剂如单克隆抗体的化学稳定性是pH依赖性的，在许多情况下，微酸性条件有利于稳定性。由于pH值的控制广泛通过添加缓冲盐来提供，因此本研究总结了乙酸盐、柠檬酸盐、组氨酸、琥珀酸盐和磷酸盐缓冲液的缓冲特性。实验得出的值与货车斯莱克在1922年提出的模型计算值基本一致。随着高浓度蛋白质制剂在生物制剂中变得越来越普遍，蛋白质的自缓冲潜力变得相关。本研究提供了pH值范围低至4.0和高达8.0的缓冲液特性信息，并表明50 mg/mL单克隆抗体显示出与6 mM柠檬酸盐或14 mM组氨酸（pH 5.06.0）相似的缓冲能力。抗体溶液的缓冲容量与蛋白质浓度呈线性关系，直至超过200 mg/mL。在220 mg/mL的蛋白质浓度下，缓冲能力类似于30 mM柠檬酸盐或50 mM组氨酸（pH 5.06.0）的缓冲能力。单克隆抗体的缓冲能力在工艺相关温度5、25和40 ℃下几乎相同。相比之下，I=0.15的离子强度的变化可以改变高达35%的缓冲能力。总之，由于抗体在有利的化学稳定性的pH范围内的有效自缓冲，常规缓冲剂赋形剂可用于高浓度蛋白质溶液的pH稳定。(c)2013年美国化学工程师学会生物技术。程序，29：480492，2013
Controlling pH is essential for a variety of biopharmaceutical process steps. The chemical stability of biologics such as monoclonal antibodies is pH-dependent and slightly acidic conditions are favorable for stability in a number of cases. Since control of pH is widely provided by added buffer salts, the current study summarizes the buffer characteristics of acetate, citrate, histidine, succinate, and phosphate buffers. Experimentally derived values largely coincide with values calculated from a model that had been proposed in 1922 by van Slyke. As high concentrated protein formulations become more and more prevalent for biologics, the self-buffering potential of proteins becomes of relevance. The current study provides information on buffer characteristics for pH ranges down to 4.0 and up to 8.0 and shows that a monoclonal antibody at 50 mg/mL exhibits similar buffer capacity as 6 mM citrate or 14 mM histidine (pH 5.06.0). Buffer capacity of antibody solutions scales linearly with protein concentration up to more than 200 mg/mL. At a protein concentration of 220 mg/mL, the buffer capacity resembles the buffer capacity of 30 mM citrate or 50 mM histidine (pH 5.06.0). The buffer capacity of monoclonal antibodies is practically identical at the process relevant temperatures 5, 25, and 40 degrees C. Changes in ionic strength of I=0.15, in contrast, can alter the buffer capacity up to 35%. In conclusion, due to efficient self-buffering by antibodies in the pH range of favored chemical stability, conventional buffer excipients could be dispensable for pH stabilization of high concentrated protein solutions. (c) 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 480492, 2013