Roche Diagnostics Deutschland GmbH, Sandhofer Str. 116, 68305, Mannheim, Germany.
F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070, Basel, Switzerland.
Pharm Res. 2018 Sep 25;35(11):215. doi: 10.1007/s11095-018-2492-4.
Biological pharmaceutical unit operations like homogenization or pooling of liquids are often performed in stirred vessels. Bottom-mounted magnetic stirrers are usually the system of choice in drug product manufacturing, because bottom-mounted magnetic stirrers are considered to be gentle mixing systems. Nevertheless, magnetic stirrers can cause shear stress and, thus, lead to protein damage.
This study uses computational fluid dynamics (CFD), because flow and shear rates cannot easily be measured at the spot of interest. The investigation utilizes CFD models, which were checked for plausibility by comparing experimental results and model outcome. The investigators first modeled macroscopic flow across a range of vessel volume capacities. Subsequently, detailed models focusing on two locations (bearing gap (2 mm - 3.5 mm) and spigot gap (40 μm - 80 μm)) were developed.
The macroscopic flow modeling showed that the direction of flow varies based on the vessel volume capacity. The detailed CFD model estimated significant flow through the bearing gap. However, the calculated shear rates in the bearing gap were always lower than the shear rates which occur directly next to the impeller tip. The CFD model calculated significantly higher shear rates in the spigot gap and flow in the lower microliter range.
Shear rates at the impeller tip are typically used as parameter to characterize stirred mixing systems. Although higher shear rates were found in the spigot gap, these higher shear rates can most likely be neglected for most applications due to non-significant flow through the spigot gap.
生物制药的单元操作，如液体的均化或混合，通常在搅拌容器中进行。在药物产品制造中，通常选择底部安装的磁力搅拌器，因为底部安装的磁力搅拌器被认为是温和的混合系统。然而，磁力搅拌器会引起剪切应力，从而导致蛋白质损伤。
本研究使用计算流体动力学（CFD），因为在感兴趣的位置不容易测量流量和剪切速率。该研究利用 CFD 模型，通过将实验结果与模型结果进行比较来检查模型的合理性。研究人员首先对一系列容器体积容量进行了宏观流动建模。随后，开发了聚焦于两个位置（轴承间隙（2mm-3.5mm）和旋塞间隙（40μm-80μm）的详细模型。
宏观流动建模表明，流动方向取决于容器体积容量。详细的 CFD 模型估计了通过轴承间隙的显著流动。然而，在轴承间隙中计算出的剪切速率总是低于叶轮尖端附近的剪切速率。CFD 模型在旋塞间隙中计算出了显著更高的剪切速率，并在较低的微升范围内产生了流动。
叶轮尖端的剪切速率通常用作表征搅拌混合系统的参数。尽管在旋塞间隙中发现了更高的剪切速率，但由于通过旋塞间隙的流量不显著，这些更高的剪切速率在大多数应用中可能可以忽略不计。
