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

Abstract

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.