Folzer Emilien, Khan Tarik A, Schmidt Roland, Finkler Christof, Huwyler Jörg, Mahler Hanns-Christian, Koulov Atanas V
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Analytical Development & Quality Control, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Basel, Switzerland.
J Pharm Sci. 2015 Dec;104(12):4034-4040. doi: 10.1002/jps.24635. Epub 2015 Sep 7.
One of the analytical tools for characterization of subvisible particles, which gained popularity over the last years because of its unique capabilities, is the resonance mass measurement technique. However, a challenge that this technique presents is the need to know the exact density of the measured particles in order to obtain accurate size calculations. The density of proteinaceous subvisible particles has not been measured experimentally yet and to date researchers have been using estimated density values. In this paper, we report for a first-time experimental measurements of the density of protein particles (0.2-5 μm in size) using particles created by stressing three different proteins using four different types of stress conditions. Interestingly, the particle density values that were measured varied between 1.28 and 1.33 g/cm(3) and were lower than previous estimates. Furthermore, it was found that although the density of proteinaceous particles was affected to a very low degree by the stress conditions used to generate them, there is relatively larger difference between particles originating from different classes of proteins (e.g., monoclonal antibody vs. bovine serum albumin).
作为一种用于表征亚可见颗粒的分析工具,共振质量测量技术因其独特的性能在过去几年中颇受青睐。然而,该技术面临的一个挑战是,为了获得准确的尺寸计算结果,需要知道被测颗粒的确切密度。蛋白质亚可见颗粒的密度尚未通过实验测量,迄今为止,研究人员一直使用估计的密度值。在本文中,我们首次报告了使用四种不同应激条件对三种不同蛋白质进行应激处理所产生的颗粒(尺寸为0.2 - 5μm)的蛋白质颗粒密度的实验测量结果。有趣的是,测得的颗粒密度值在1.28至1.33 g/cm³之间,低于先前的估计值。此外,研究发现,尽管用于生成蛋白质颗粒的应激条件对其密度的影响程度很低,但源自不同类别蛋白质(例如单克隆抗体与牛血清白蛋白)的颗粒之间存在相对较大的差异。