This study aimed to prepare a complex of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and 6CN10, a poorly water soluble 2-aminothiophene derivative with antifungal properties, by freeze-drying technique. The complex was characterized by thermal analysis, infrared/Raman spectroscopy, X-ray diffraction and scanning electron microscopy. In addition, we used the data of the phase solubility study, 1 H, and 2D NMR spectroscopy and molecular modeling in order to investigate the interactions between 6CN10 and HP-β-CD. The apparent solubility of 6CN10 with HP-β-CD increased more than 29 fold. The phase solubility assay in water at 25 ºC showed an A P -type curve, with an apparent stability constant K 1:1 and K 1:2 of 96 and 0.1989 M -1 , respectively. The results of IR, NMR and docking indicate that 6CN10 is able to form complexes with HP-β-CD (1:1 and 1:2 stoichiometric ratios), generating the formation of inclusion and preferably, non-inclusion complexes. The antifungal activity against Cryptococcus neoformans demonstrated the superior performance of the complex (46.66 μg mL -1 ) when compared with the free drug (166.66-333.33 μg mL -1 ). The present study provides useful information for the potential application of complexation with low soluble compounds and about the type of complex formation between 6CN10 and HP-β-CD.