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.