Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms
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This work aimed to synthesize a novel β-cyclodextrin derivative, itaconyl-β-cyclodextrin to evaluate whether albendazole inclusion complexes with the new β-cyclodextrin derivative-improved albendazole dissolution efficiency and its anthelminthic activity. The new derivative was thoroughly evaluated and characterized, and an average degree of substitution of 1.4 per cyclodextrin molecule was observed. Albendazole:itaconyl-β-cyclodextrin complexes were prepared by spray drying procedures and investigated using phase solubility diagrams, dissolution efficiency, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared, scanning electronic microscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Phase solubility diagrams and mass spectrometry studies showed that the inclusion complex was formed in an equimolar ratio. Stability constant values were 602 M−1 in water, and 149 M−1 in HCl 0.1 N. Nuclear magnetic resonance experiments of the inclusion complex showed correlation signals between the aromatic and propyl protons of albendazole and the itaconyl-β-cyclodextrin inner protons. The studies indicated solid structure changes of albendazole included in itaconyl-β-cyclodextrin. The maximum drug release was reached at 15 min, and the inclusion complex solubility was 88-fold higher than that of the pure drug. The in vitro anthelmintic activity assay showed that the complex was significantly more effective than pure albendazole.
KeywordsCyclodextrins Synthesis Poorly water-soluble drug Albendazole Physicochemical characterization
J.P. and A.G. are grateful to CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas) for a Doctoral and a Posdoctoral Fellowship.
This work was supported by the Universidad Nacional de Rosario, CONICET (Project No. PIP 112-201001-00194) and Agencia Nacional de Promoción Científica y Tecnológica (Project No. PICT 2006-1126).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All institutional and national guidelines for the care and use of laboratory animals were followed.
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