Ternary naproxen:β-cyclodextrin:polyethylene: glycol complex formation

Abstract

[EN]The aim of this study was to investigate the effect of the presence of the water-soluble polymer polyethylene glycol (PEG)—MW=35000 g/mol—on the complexation of the phototoxic anti-inflammatory drug naproxen, in its sodium salt form, with β-cyclodextrin (β-CD). The data revealed that the polymer does not interact with the uncomplexed naproxen whereas it does with the β-CD. The presence of different proportions of PEG, in the 0–1% (w/w) range, systematically lowers Kapp of the formation of the naproxen:β-CD inclusion complex. The reason for the decrease in the complexed drug is the presence of other competing equilibria, the first one is an interaction of the polymer with the β-CD, which in turn reduces the amount of free CD available for including the naproxen, and the second is the formation of a naproxen:β-CD:PEG ternary complex with lower affinity than the binary complex. The binding constant of these processes are K2=(4.5±1.0)×105 M−1 and K3=870±19 M−1, respectively. In addition the presence of the PEG produces an important change in the driving force of the complex formation. In this case the process is enthalpically unfavoured and entropically favoured; these are typical characteristics of processes governed by hydrophobic interactions.