Benznidazole (BNZ) is the main drug used for the treatment of Chagas disease. However, its low aqueous solubility limits its efficacy. In this study, we have prepared host-guest inclusion complexes of BNZ with beta-cyclodextrin (beta-CD) in solid phase and assessed the influence of the co-solvents triethanolamine (TEA) and 1-methyl-2-pyrrolidone (NMP) for improving the drug dissolution performance. The physicochemical properties of prepared spray-dried (SD) particles and physical mixtures (PM) were carefully monitored using FTIR, XRD and SEM images. The used co-solvents affected beta-CD-drug interactions, the structural properties and drug dissolution behavior of particles. TEA did not improve the solubilizing effect of beta-CD, while NMP was able to enhance drug dissolution performance in both SD and PM complexes. These promising results support the use of specific co-solvents with CD as a new raw material for insoluble compounds. The studied solid dispersions showed promising features to improve BNZ efficacy against Chagas disease.