First solid-state NMR spectroscopy evaluation of complexes of benznidazole with cyclodextrin derivatives

•Evidences for one molecule in the asymmetric unit of crystalline benznidazole.•Solid dispersions of benznidazole (BZL) and cyclodextrins (CDs) were studied.•Evidences for the inclusion complex formation between BZL and Me-β-CD.•BZL conformation differs from raw crystal and benzene is encapsulated into the CD.•Formation of the inclusion complex enables stabilizing amorphous benznidazole. Complexation of benznidazole (BZL), a drug of choice for the treatment of Chagas’neglected disease, with cyclodextrin (CD) derivatives was analyzed by solid-state NMR. 13C cross polarization/magic angle spinning spectra were recorded from BZL and from BZL:β-CD, BZL:methyl β-CD and BZL:hydroxypropyl β-CD complexes, which were obtained by the solvent evaporation technique. No significant evidence was obtained on BZL inclusion complexes involving either β-CD or hydroxypropyl β-CD. Conversely, BZL:methyl β-CD displayed BZL resonances characteristic of an amorphous drug and data analysis confirmed the presence of stable BZL:methyl β-CD inclusion complexes, with benzene encapsulated into the host cavity. Further evidences on complex structure and dynamics were obtained from proton and carbon spin–lattice relaxation times in the rotating frame. These data are consistent with a common guest–host spin reservoir. The BZL interaction with methyl β-CD provided a route to stabilize amorphous BZL. Physical mixtures with identical BZL and CD compositions were also studied for comparison.