Comprehensive Characterisation of the Ketoprofen-β-Cyclodextrin Inclusion Complex Using X-ray Techniques and NMR Spectroscopy

Racemic ketoprofen (KP) and beta-cyclodextrin (beta-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of beta-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of beta-CD and KP. NMR results indicated that KP/beta-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M-1, showing that KP is quite strongly associated with beta-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/beta-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/beta-CD complex, only method 3 is suitable.