A Research Paper Published in Journal of Molecular Liquids

This study represents detailed investigation of the influence of β-cyclodextrin as well as its hydroxypropylated, randomly methylated, and alkylsulfonated derivative on the solubility of the drug nabumetone in water and in simulated biorelevant media. Nabumetone with the mentioned β-cyclodextrins forms inclusion complexes in aqueous solutions, and the complexation was investigated by fluorescence spectroscopy, isothermal titration microcalorimetry, high-resolution mass spectrometry, and 1D and 2D NMR spectroscopy. All used β-cyclodextrins increased the solubility of nabumetone several times, with the fact that the alkylsulfonated derivative increased it by as much as 170 times. It has been unequivocally proven that nabumetone forms inclusion complexes with β-cyclodextrin and its derivatives in a stoichiometric ratio of 1:1, and the values of the stability constants calculated using different techniques and methods showed a very good mutual agreement. The simultaneous existence of two different structures of the inclusion complex with different orientations of nabumetone in the cavity of β-cyclodextrin was experimentally proven for the first time based on detailed investigations by NMR spectroscopy, which was confirmed earlier in silico investigations. These results are the basis for the following investigations of the complexation of nabumetone with β-cyclodextrins in the solid state, which would potentially obtain new formulations of this drug with improved properties.

The published results are part of David Klarić's doctoral dissertation. The research was carried out within the Croatian Science Foundation project entitled "Preparation, characterization, and biocompatibility studies of novel drug/cyclodextrin and drug/dextrin-based nanosponge supramolecular complexes with enhanced functionality" (IP-2022-10-6033).