During high-concentration protein drug product compounding, the property difference between the drug substance solution and the buffer excipient solution can potentially cause the formation of stratified layers, which may prohibit effective mixing. In this study, mixing of two stratified liquids in an unbaffled tank with an angle-mounted impeller was investigated using both experiments and computational fluid dynamics (CFD) simulations. The results revealed that the mixing time under the stratified conditions could be over an order of magnitude longer than that predicted by a commonly used blend time correlation. Further analysis showed that the observed long mixing time occurred when the buoyancy force due to density difference between the liquids was dominant over the impeller stir and was correlated with high Richardson number. The study also looked into the impact of factors such as liquid height and impeller size, and a new correlation was proposed based on the experimental data.

中文翻译：

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分层混溶液体在无挡板储罐中的混合及其在高浓度蛋白药物产品生产中的应用

在高浓度蛋白质药物产品混合过程中，药物溶液和缓冲赋形剂溶液之间的性质差异可能会导致分层的形成，从而可能会阻止有效混合。在这项研究中，使用实验和计算流体动力学（CFD）模拟研究了在无折流罐和角形叶轮中两种分层液体的混合。结果表明，分层条件下的混合时间可能比通常使用的混合时间相关预测的时间长一个数量级。进一步的分析表明，当液体之间的密度差引起的浮力在叶轮搅拌中占主导地位，并且与高Richardson数相关时，观察到的长混合时间发生了。