오메프라졸과 gamma-시클로덱스트린과의 복합체 형성 및 제제학적 특성

Interaction between Omeprazole and gamma-Cyclodextrin

The interaction of omeprazole(OMP) with gamma-cyclodextrin(gamma-CyD) was investigated by solubility study and the complexation was confirmed by means of UV/VIS spectrophotometer, circular dichroism, differential scanning calorimeter, and 1H nuclear magnetic resonance spectra. The stability, dissolution rate, and partition coefficient of the complex were measured. The results present that the benzimidazole moiety and a part of pyridine ring containing sulfur atom of OMP might be included into the cavity of gamma-CyD and the formation type of inclusion complex appeared to be Bs. The stoichiometric ratio of OMP to gamma-CyD in the complex was found to be 1 : 1 and the stability constant of the complex was found to be 97.1M-1. And the dissolution rate of OMP was markedly increased by inclusion complex formation with gammer-CyD, and so it was above 90% in 5 min, from solid complex. Oil to water partition coefficient of OMP-gamma-CyD complex was 60, which is significantly higher than that of OMP itself, 36.4. The degradation rate constant of OMP were greater than OMP-gamma-CyD complex in aqueous solutions of various pHs, and the half lives of OMP and OMP-gamma-CyD at pH 9 were 279.2 and 509.9 days, respectively, showing that the complex was more stable than OMP, therefore it was thought that OMP was stabilized by inclusion formation with gamma-CyD.