Solid-state characterization and dissolution profiles of the inclusion complexes of omeprazole with native and chemically modified β-cyclodextrin

The aim of this work was to investigate the formation of the inclusion complex between omeprazole (OME), a benzimidazolic derivative and a methylated cyclodextrin, methyl-beta-cyclodextrin (M beta CD), with an average degree of substitution of 0.5. Inclusion complex between OME and beta-cyclodextrin (beta CD), a natural cyclodextrin, was used as reference. In aqueous media, apparent stability constants (K-s), which describe the extent of formation of the complexes, have been determined by UV spectroscopy and H-1 NMR experiments. The stoichiometry of the complexes was found to be 1: 1 mol:mol OME:cyclodextrin (CD) and the value of Ks was higher for OME:M beta CD than for OME:beta CD inclusion complexes. Solid binary systems of OME and CDs were prepared by different techniques, namely kneading, spray-drying and freeze-drying. The formation and physicochemical characterization of solid inclusion complexes were investigated by differential scanning calorimetry (DSC), Fourier transform-infrared (FTIR), X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The results show that freeze-drying method produces true inclusion complexes between OME and both CDs. In contrast, crystalline drug was detectable in kneaded and spray-drying products. The dissolution of OME from the binary systems was studied to select the most appropriate system for the development of a buccal drug delivery formulation. It was concluded that the preparation technique played an important role in the dissolution behaviour of the drug and the inclusion complex between OME and M beta CD obtained by spray-drying and freeze-drying allowed better performances. (C) 2007 Elsevier B.V. All rights reserved.