Early Stage Pharmaceutical Development, Genentech, Inc. South San Francisco, California 94080, USA.
J Pharm Sci. 2012 Mar;101(3):1012-20. doi: 10.1002/jps.23002. Epub 2011 Dec 13.
Highly concentrated protein solutions are becoming increasingly commonplace within the biopharmaceutical industry as more products are developed that feature high doses of drug intended for subcutaneous administration. An as-yet undeveloped subclass of these products feature multiple proteins coformulated together in high-concentration protein mixtures. Previous work has illustrated that the viscosity of aqueous solutions of various proteins at high concentrations can be remarkably different across otherwise similar molecules. This work characterizes the viscosity behavior of mixtures of such proteins, primarily monoclonal antibodies, and shows that a simple mixing rule first proposed by Arrhenius predicts the viscosity of an arbitrary mixture. This approach is shown to successfully calculate the viscosity of mixtures of proteins ranging up to 250 mg/mL total protein concentration and approximately 1700 cP at different ionic strengths and with accuracy errors of less than 10%. Only information about the viscosity of the isolated protein components of the mixture is required for the calculations.
高浓度蛋白质溶液在生物医药行业中越来越普遍，因为越来越多的产品被开发出来，这些产品具有高剂量的药物，用于皮下给药。这些产品中尚未开发的一个子类是将多种蛋白质共同配制在高浓度蛋白质混合物中。以前的工作表明，在其他方面相似的分子中，高浓度下各种蛋白质的水溶液的粘度可以有显著的不同。这项工作描述了此类蛋白质（主要是单克隆抗体）混合物的粘度行为，并表明由阿伦尼乌斯首次提出的简单混合规则可以预测任意混合物的粘度。该方法成功地计算了在不同离子强度下总蛋白浓度高达 250mg/mL 且粘度约为 1700cP 的蛋白质混合物的粘度，且准确度误差小于 10%。计算仅需要混合物中分离蛋白质组分的粘度信息。
