BENZNIDAZOLE AND CYCLODEXTRIN BENZNIDAZOLE COMPLEXES STUDIED BY 13C SOLID-STATE NMR

PRIOTTI, J.; FERREIRA, M; LAMAS, M. C.; LEONARDI, D.; SALOMON, C.; NUNES, T.

Córdoba

Congreso; III Reunión Internacional de Ciencias Farmacéuticas RICIFA 2014; 2014

Benznidazole, N-benzyl-2-(2-nitroimidazol-1-yl) acetamide (BZL) is the drug of choice for treating Chagas? disease but its absorption in gastrointestinal fluids is limited due to its poor aqueous solubility. The formation of water-soluble inclusion complexes of BZL with cyclodextrins (CDs), cyclic carbohydrates with a hydrophobic cavity and hydrophilic exterior, is expected to increase the drug solubility, which is strongly dependent on solid-state properties, like polymorphism. 13C solid-state NMR enables studying these systems by probing local changes on electronic environment and/or mobility of carbon atoms, under non invasive and non destructive modes. 13C cross polarization/ magic angle spinning (CP/MAS) NMR spectra were obtained from BZL and from BZL:cyclodextrin (CD), BZL:methyl -CD and BZL:hydroxypropyl -CD, in 1:1 and 1:2 (mol:mol) drug:CD ratio combinations, which were prepared by solvent evaporation. Solid-state 13C NMR presented evidence for the absence of chemical interaction between BZL and CD, because BZL carbon signals recorded from the pure drug and from BZL:CD can be superimposed. However, when BZL:CDs were prepared with methyl -CD, hence with higher CD hydrophobic cavity, BZL spectral changes occur, particularly in the benzene frequency region (namely, a new signal is identified at 139.4 ppm). Such effect, which appears not depend on the drug:CD ratio, clearly indicates the inclusion of BZL in methyl -CD through its benzene ring. A similar species is assigned in BZL:hydroxypropyl -CD spectra, which corresponds to a complex with lower concentration, owing to the presence of lower intense signals. Solid-state NMR was a valuable approach to elucidate the different oral bioavailability of these systems.