Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

Two different formulations of cyclodextrin nanosponges (CDNS), obtained by polycondensation of β-cyclodextrin with ethylenediaminetetraacetic acid dianhydride (EDTAn), were treated with aqueous solutions of ibuprofen sodium salt (IbuNa) affording hydrogels that, after lyophilisation, gave two solid CDNS-drug formulations. ¹H fast MAS NMR and ¹³C CP-MAS NMR spectra showed that IbuNa was converted in situ into its acidic and dimeric form (IbuH) after freeze-drying. ¹³C CP-MAS NMR spectra also indicated that the structure of the nanosponge did not undergo changes upon drug loading compared to the unloaded system. However, the ¹³C NMR spectra collected under variable contact time cross-polarization (VCT-CP) conditions showed that the polymeric scaffold CDNS changed significantly its dynamic regime on passing from the empty CDNS to the drug-loaded CDNS, thus showing that the drug encapsulation can be seen as the formation of a real supramolecular aggregate rather than a conglomerate of two solid components. Finally, the structural features obtained from the different solid-state NMR approaches reported matched the information from powder X-ray diffraction profiles.