Effect of Substitution Degree and Homogeneity on Cyclodextrin-Ligand Complex Stability: Comparison of Fenbufen and Fenoprofen Using CD and NMR Spectroscopy.

The stability of host-guest complexes of two NSAID drugs with similar physicochemical properties, fenbufen and fenoprofen, was investigated by comparing induced circular dichroism and 1 H nuclear magnetic resonance methods using eight cyclodextrins of different degrees of substitution and isomeric purity as guest compounds. These cyclodextrins include native β-cyclodextrin (BCyD), 2,6-dimethyl-β-cyclodextrin 50 (DIMEB50), 80 (DIMEB80) and 95% (DIMEB95) isomerically pure versions, low-methylated CRYSMEB, randomly methylated β-cyclodextrin (RAMEB) and 4.5 and 6.3 average substitution grade hydroxypropyl-β-cyclodextrin (HPBCyD). The stability constants obtained by the two methods show good agreement in most cases. For fenbufen complexes, there is a clear trend that the stability constant increases with the degree of substitution while isomer purity has a smaller effect on the magnitude of stability constants. A significant difference was found in the case of DIMEB50 when compared to DIMEB80/DIMEB95, while the latter two are similar. In the fenbufen-fenoprofen comparison, fenbufen, with its linear axis, gives a more stable complex, while fenoprofen shows lower constants and poorly defined trends.