Improvement of Solubility and Dissolution of Ketoconazole by Inclusion with Cyclodextrin

시클로덱스트린과의 포접에 의한 케토코나졸의 용해성 및 용출 증가

  • Park, Gee-Bae (College of Pharmacy, Chung-Ang University) ;
  • Ann, Hong-Jik (College of Pharmacy, Chung-Ang University) ;
  • Chang, Young-Soo (Narcotics Control Division, Bureau of Pharmaceutical Affairs, Ministry of Health and Social Affairs) ;
  • Seo, Bo-Youn (College of Pharmacy, Chung-Ang University) ;
  • Lee, Kwang-Pyo (College of Pharmacy, Chung-Ang University)
  • Published : 1994.06.20

Abstract

Inclusion complexes of ketoconazole (KT) with ${\alpha}-$, ${\beta}-cyclodextrin$ (CD) and dimethyl-${\beta}-cyclodextrin$ $(DM{\beta}CD)$ in a molar ratio of 1:2 were prepared by freeze-drying and solvent evaporation methods. The interactions of KT with ${\alpha}-CD$, ${\beta}-CD$ and $DM{\beta}CD$ in aqueous solution and in solid state were investigated by solubility study, infrared (lR) spectroscopy and differential scanning calorimetry (DSC). The stability constant of $KT-DM{\beta}CD$ inclusion complex (lC) was found to be the largest among three inclusion complexes. Clear differences in IR spectra and DSC curves were observed between inclusion complexes and physical mixtures (PM) of KT-CDs. It was also shown by IR spectra and DSC curves that solvent evaporation method might be. superior to the freeze-drying method in preparing the inclusion complexes of KT-CDs. The dissolution rate of KT was markedly increased by inclusion complex formation with CDs in the buffer solution at pH 4.0 and pH 6.8. The mean dissolution time (MDT,min), which represents the rapidity of dissolution, was in the order of $KT-DM{\beta}CD$ IC (3.20) < $KT-{\beta}-CD$ IC (4.36) < $KT-{\alpha}-CD$ IC (6.99) < $KT-{\alpha}-CD$ PM (17.46)< $KT-{\beta}-CD$ PM (19.36) < $KT-{\beta}-CD$ PM (28.53). The dissolution rates of KT-CD ICsprepared by solvent evaporation method were faster than those of KT-CD ICs prepared by freeze-drying method.

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