The systematic study of excipients in the pre-formulation stage allows to find more promising excipients, saving time, cost, and materials. Raman imaging allowed not only to study of the miscibility of the excipients with the drug, but also to find regions of API overload. The ternary diagrams obtained from mixture DoE indicate the DHI value is more suitable than the STD from the histograms for miscibility studies, since in the former the information is complementary. Nevertheless, despite the vast amount of information obtained from the ternary diagrams, their evaluation should be accompanied with the evaluation of the Raman images. We also highlighted how solubility behavior can affect the sample surface and, consequently, its homogeneity. This is particularly important in the overload regions; in cases of unsuitable solubilization, heterogenous surface were generated and DHI works well as an indicative of immiscibility. However, in cases of good solubility between drug and excipient, as showed by butamben and Capryol ® 90, the good dispersion of API in the liquid lipid, caused it to be homogeneously distributed throughout the analyzed surface. Therefore, DHI values were low when they should be high. This can be an indicative of phase separation and just a surface analysis