Phase Solution and Solution Recrystallization Equilibrium Constants of Hydroxypropyl-β-cyclodextrin Complexes with Nifedipine and Nicardipine Hydrochloride

DOI
  • Li Yingpeng
    Faculty of Pharmaceutical Sciences, Tokyo University of Science Research Institute for Science and Technology, Tokyo University of Science
  • Goto Satoru
    Faculty of Pharmaceutical Sciences, Tokyo University of Science Research Institute for Science and Technology, Tokyo University of Science
  • Shimada Yohsuke
    Faculty of Pharmaceutical Sciences, Tokyo University of Science Research Institute for Science and Technology, Tokyo University of Science
  • Makino Kimiko
    Faculty of Pharmaceutical Sciences, Tokyo University of Science Research Institute for Science and Technology, Tokyo University of Science

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抄録

The structure of a cyclodextrin (CD) complex depends on the factors such as the guest hydrophobic molecule, steric hindrance, and charge. Apart from thermal analysis, crystal analysis, and nuclear magnetic resonance (NMR), the phase solution graph can be used to analyze and insure this structure. In this study, solubility and dissolution rate of nifedipine (NIF) [or nicardipine (NIC) hydrochloride]/hydroxypropyl-β-cyclodextrin (HP-β-CD) complexes were investigated to surmise the structures of the complexes. Solubility improvements of NIF and NIC in HP-β-CD solution revealed the possible interaction between NIF/HP-β-CD and NIC/HP-β-CD complexes. The values of the solubility equilibrium constant and the recrystallization equilibrium constant indicated that NIF interacts with HP-β-CD in an equimolar fashion because of its hydrophobicity. In contrast, NIC interacts with HP-β-CD through multiple drug links, probably because of its ionization and hydrophilicity. The study on phase solution and dissolution rate of CD complex could be a novel aspect to distinguish the complex structure when there is neither UV/vis spectrum (Job's plot of spectroscopy) nor NMR data could quantify the distinction of the complexes, such as NIF or NIC/HP-β-CD complexes.

収録刊行物

  • 薬剤学

    薬剤学 76 (4), 267-273, 2016

    公益社団法人 日本薬剤学会

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