Diloxanide furoate binary complexes with β-, methyl-β-, and hydroxypropyl-β-cyclodextrins: inclusion mode, characterization in solution and in solid state and in vitro dissolution studies

Abstract

The purpose of this study was to investigate the effect on solubility and dissolution rate of binary complexes of β-(βCD), methyl-(MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) with diloxanide furoate (DF). The complexation in solution was evaluated by phase solubility studies and 1H nuclear magnetic resonance (NMR). Enhanced water solubility of DF was obtained with the DF:MβCD system (61-fold). The mode of inclusion was supported by NMR experiments, which indicated that real inclusion complexes were formed between DF and MβCD or HPβCD. Solid state analysis was performed using infrared and thermal methods, which suggested the formation of true inclusion complexes of DF with two derivatized cyclodextrins, MβCD and HPβCD, and an exclusion complex with βCD when the systems were prepared by freeze-dried technique. Dissolution studies conducted in simulated gastric fluid (2 h) and subsequent simulated intestinal fluid (next 4 h) showed increased dissolution rate of DF from the freeze-dried systems with βCD, MβCD, and HPβCD (85; 77 and 75% of dissolved drug at 5 min, respectively) and 100% of the drug dissolved at 150 min for the three systems. The enhancement of the solubility and the dissolution of DF observed make these complexes promising candidates for the preparation of oral pharmaceutical formulations.