This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol (CAR), cinnarizine (CIN) or R3040 on drug solubilization in a two-compartment lipolysis model. Correlation of drug log or solubility in SNEDDS with drug solubilization during lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1 (1:1, /) and Kolliphor RH40, with ethanol at 10% (/) were used. SNEDDS were named F65, F55 and F20 (numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS (F0) were also analyzed. While the ranking order of drug solubilization was F65=F55=F20>F0 for CAR; F65=F55>F20>F0 for CIN and F65=F55=F20>F0 for R3040 - with higher CAR solubilization than for R3040 and CIN - the ranking of of CAR, CIN and R3040 in SNEDDS was F65F20 and F65>F55>F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high in SNEDDS did not reflect high drug solubilization. As CAR (log 3.8) showed higher solubilization than CIN (log 5.8) and R3040 (log 10.4), a correlation between drug log and drug solubilization was observed.