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.

Keywords:

• Diloxanide furoate
• cyclodextrin
• complexation
• mode of interaction
• solid state characterization
• in vitro dissolution

Acknowledgements

Dr Gloria M. Bonetto’s assistance and her helpful discussion in NMR measurements is highly appreciated. We also want to thank Ferromet S.A. (Roquette’s agent in Argentina) for their donation of cyclodextrins.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

Consejo Nacional de Investigaciones Científicas y Técnicas

Universidad Nacional de Córdoba

‘Fondo para la Investigación Científica y Tecnológica’Préstamo BID PICT 2012-1461The authors wish to acknowledge the support from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and the Universidad Nacional de Córdoba, both of which provided grants and facilities for this investigation. Financial support from ‘Fondo para la Investigación Científica y Tecnológica’ (FONCYT) Préstamo BID PICT 2012-1461 and ‘Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba’ (SECyT-UNC), is greatly acknowledged.