The low solubility of BTB in Dhaykol resulted in API clusters at higher concentrations (Figure and). The chemical map of cetyl palmitate in 14.3% (w/w) BTB shows spots with absence of both the drug and Dhaykol (deep blue in Figure , left and middle). In the BTB map it is clear that the API agglomerates in this region. In NLC, Dhaykol should work as a 'bridge' and it needs to be miscible with the solid lipid and to solubilize the drug, simultaneously. However, it can be clearly seen that, in this concentration, its solubilization capacity is poor and therefore there are clusters of pure BTB in cetyl palmitate. These clusters generated two populations in histograms of CP and BTB, and longer tails in Dhaykol histograms (Figure ). The presence of agglomerates caused a DHI increase of 1.5 or 2.0 units (Figure ). Figure shows the results for 25 % (w/w) BTB where the above-mentioned situation was confirmed. As a matter of fact, even at the visible image it was possible to see lumps (Figure ), that were confirmed by Raman imaging to be clusters of the drug. It is interesting to note that Raman spectroscopy allowed the detection of those clusters at the lower concentration of 14.3% (w/w) BTB, which is very interesting in preformulation studies. The miscibility problems were observed since the initial analysis and there were no alterations after 7 days (data no shown).