Interactions between naproxen and maltoheptaose, the non-cyclic analog of?-cyclodextrin

Abstract

The crystallinity of naproxen in solid combinations with amorphous maltoheptaose, the non-cyclic analog of β-cyclodextrin, was assessed using differential scanning calorimetry supported by X-ray powder diffractometry. Cogrinding induced a decrease in drug crystalinity to an extent which depended on the grinding time, and was most pronounced for the combination of equimolecular composition. Thermal analysis showed that the mechanism behind the conversion of crystalline naproxen into the amorphous state by cogrinding with maltoheptaose differed from that with randomly substituted, amorphous β-cyclodextrins. Interactions of naproxen with maltoheptaose in aqueous solution were studied by means of fluorescence spectroscopy, phase-solubility analysis, and computeraided molecular modelling. Maltoheptaose can wrap up naproxen, taking on a cyclic conformation and forming a ‘pseudo’ inclusion complex (apparent binding constant K1: 1 = 1.0 × 103 (−20%) L mol−1 at 25 °C) which is about as stable as the true inclusion complex with β-cyclodextrin in the lowest temperature range (0-100 K). A better complexing ability for naproxen in terms of binding constant values, however, was displayed by both native and derivatized β-cyclodextrins, the ‘hosts’ with covalently-bound cyclic structures.