Comparative study of oxaprozin complexation with natural and chemically-modified cyclodextrins in solution and in the solid state

The complexing, solubilizing and amorphizing abilities toward oxaprozin (a poorly water-soluble anti-inflammatory agent) of some beta-cyclodextrin derivatives (hydroxypropyl-beta Cd, heptakis-2,6-di-O-methyl-beta Cd (DIMEB) amorphous randomly substituted methyl-beta Cd (RAMEB) and semi-crystalline methyl-beta Cd (CRYSMEI')) were investigated and compared with those of natural (alpha-, beta-, gamma-) cyclodextrins. The role of both the cavity size, the amorphous or crystalline state and the presence and type of substituent on the ability of cyclodextrins in establishing effective interactions with the drug has been evaluated. Equimolar drug-cyclodextrin solid systems were prepared by blending, kneading, co-grinding, sealed-heating, coevaporation, and colyophilization. Drug-carrier interactions were studied in both the liquid and solid state by phase-solubility analysis, differential scanning calorimetry, X-ray powder diffractometry, FT-IR spectroscopy and scanning electron microscopy. beta Cd showed the best performance among the natural Cds, indicating that its cavity was the most suitable for accommodating the drug molecule. The presence of substituents on the rim of the beta Cd cavity significantly improved its complexing and solubilizing effectiveness towards the drug, and methylated derivatives were better than the hydroxy-propylated ones The amorphous nature of the partner was also important: among the examined methyl-derivatives, RAMEB proved to be the most effective in performing solid state interactions and in improving drug wettability and dissolution properties.