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

Abstract

Racemic ketoprofen (KP) and β-cyclodextrin (β-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 β-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of β-CD and KP. NMR results indicated that KP/β-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M−1, showing that KP is quite strongly associated with β-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/β-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/β-CD complex, only method 3 is suitable.

The counteracting influence of 2-hydroxypropyl substitution and the presence of a guest molecule on the shape and size of the β-cyclodextrin cavity

“…[30][31][32][33] Yet, it is difficult to obtain single crystals of HP-b-CD-guest inclusion complexes, while there are several studies on single crystal X-ray diffractometry of native b-CD-guest inclusion complexes. [34][35][36][37][38] Commercially available samples of HP-b-CDs show high variability in their properties 15 because of the difference in the site of substitution and poly-dispersity in the DS of the samples. Two samples of HP-b-CDs with DS values of 4.2 and 4.3 showed a contrasting effect in the treatment of Niemann-Pick disease type C in mice; the former delayed the neurological symptoms while the latter did not.…”