Benznidazole and cyclodextrin benznidazole complexes studied by 13C solid state NMR

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

Congreso; III Reunión Internacional de Ciencias Farmacéuticas RICIFA; 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. The aim of this study was to evaluate the formation of such complexes by 13C solid-state NMR. This technique enables the analysis of these systems by probing local changes on electronic environment and/or mobility of carbon atoms, under non invasive and non destructive modes. The BZL-CDs complexes were prepared by the solvent evaporation method at 1:1 and 1:2 (mol:mol) drug:CD ratio. 13C cross polarization/ magic angle spinning (CP/MAS) NMR spectra were obtained from BZL and from the prepared BZL:b-cyclodextrin (CD), BZL:methyl ?Ò-CD and BZL:hydroxypropyl b-CD complexes. The results of this solid-state 13C NMR study allowed us to postulate 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 b-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 b-CD through its benzene ring. A similar species is assigned in BZL:hydroxypropyl b-CD spectra, which corresponds to a complex with lower concentration, owing to the presence of lower intense signals. In conclusion, solid-state NMR was a valuable approach to elucidate the different oral bioavailability of these systems.