Solid-state NMR Studies on Albendazole and Cyclodextrin Albendazole Complexes

FERREIRA, M; GARCÍA, A.; LEONARDI, D.; SALOMON, C.; LAMAS, M. C.; NUNES, T.

Cordoba

Congreso; Ricifa 2014; 2014

Ricifa

Albendazole (ABZ), methyl [5-(propylthio)-1-H-benzimidazol-2-yl] carbamic acid methyl ester is one of the most effective broad-spectrum anthelmintic agents, albeit its poor solubility in water. This fact has been of major concern regarding the preparation of ABZ formulations. ABZ:beta-cyclodextrin complexes are among the several approaches that have been used to improve the physicochemical properties of ABZ. However, solubility is strongly dependent on solid-state properties, particularly when polymorphism occurs, which solid-state NMR enables probing under non invasive and non destructive modes. 13C cross polarization/ magic angle spinning (CP/MAS) and 15N CP/MAS NMR spectra were obtained from ABZ and from ABZ:beta-cyclodextrin (CD), ABZ:methyl beta-CD, ABZ:hydroxypropyl beta-CD and ABZ: citrate beta-CD systems, which were obtained by solvent evaporation. Solid-state 13C and 15N NMR spectra suggest two different kinds of chemical interaction between ABZ and the CDs used in the present study. For CDs with higher hydrophobic cavity (methyl beta-CD and hydroxypropyl beta-CD), were detected three ABZ molecules with different imidazole ring electronic environments, most probably corresponding to free ABZ and to two ABZ tautomers. On the other hand, the spectra from complexes of ABZ with beta-CD and citrate beta-CD are consistent with ABZ carbamate NH groups being involved in hydrogen bonding, and this effect is more pronounced for ABZ: citrate beta-CD. Solid-state NMR data has contributed therefore to explain the differences in ABZ solubility enhancement found with the different CDs. Acknowledgements: The authors express their gratitude to Fundação para a Ciência e a Tecnologia - Portugal (project RECI/QEQ-QIN/0189/2012) for the financial support. Keywords: Albendazole, cyclodextrin, solid-state NMR.