Proton magnetic resonance ((1)HNMR) spectroscopy and physicochemical studies of zaleplon-hydroxypropyl-β-cyclodextrin inclusion compounds.

Proton magnetic resonance spectroscopy ((1)HNMR) studies on inclusion compounds of zaleplon with hydroxypropyl-β- cyclodextrin (HPβCD) were carried out in order to elucidate the strength and binding mode of association. Chemical shift measurements revealed that inclusion complexes of zaleplon and HPβCD were formed by penetration of aromatic rings into the HPβCD cavity from the wider rim side with deep penetration of the amide-substituted ring while inclusion of the cyano-substituted pyrazole ring was shallow. A higher magnitude of ΔδH-3' and ΔδH-5' protons of HPβCD indicated higher stability of the lyophilized product than the kneaded one. Even from the values of ΔδH-5'/ΔδH-3', it could be concluded that zaleplon deeply penetrated inside the HPβCD cavity in the lyophilized product as compared to the kneaded product. The stoichiometry of the inclusion complexes was assessed to be a 1:1 molar ratio with an AL-type of phase solubility curve and a stability constant of 57.89 ± 1.82 M-1, according to Higuchi and Connors. In the case of dissolution experiments, a lyophilized product displayed a higher release rate of zaleplon (DE30: 77.64 ± 5.74) than the kneaded complex and physical mixture.