Inclusion complex of cinnarizine withβ-cyclodextrin in aqueous solution and in solid state

Abstract

Inclusion complex formation of cinnarizine (CN) with β-cyclodextrin (β-CD) in aqueous solution and in solid state was confirmed by the solubility method, powder X-ray diffractometry, differential scanning calorimetry (DSC) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy. The apparent stability constant, K′, of the complex in water at 20°C was estimated as 6.2×10³M⁻¹. The stoichiometry of the complex was given as the ratio 1∶2 of CN to β-CD. The dissolution rate of CN/β-CD complex which could be prepared three different methods, coprecipitation method, neutralization method and spray-drying method, was much more rapid than intact CN, i.e., about 30 times or more. The degradation of CN in acidic solution was found to be of pseudo first-order reaction. The pseudo first-order rate constant with β-CD decrease with an increase in concentration of β-CD at pH 1.20. The inclusion complex prepared by spray-drying method was very stable under heating conditions and under high humid conditions. There was no difference in the bioavailability of CN between oral administration of β-CD complex and that of CN alone. The absorption of CN decreased significantly when CN administered with NaHCO₃. However, there was observed no decrease in the case of CN/β-CD inclusion complex.