Artemether/hydroxypropyl-beta-cyclodextrin host-guest system: characterization, phase-solubility and inclusion mode

Bioorg Med Chem. 2009 Sep 1;17(17):6311-7. doi: 10.1016/j.bmc.2009.07.060. Epub 2009 Jul 28.

Abstract

An inclusion complex of the antimalarial artemether (ATM) in hydroxypropyl-beta-cyclodextrin (HPbetaCD) was prepared and characterized. The phase-solubility diagram for the drug showed an increase in water solubility and gave an apparent binding constant of 220 M(-1). According to (1)H NMR and 2D NMR spectroscopy (ROESY), the inclusion mode involves two CH(3) from the drug orientated in the HPbetaCD cavity. The complex was characterized by Powder X-ray diffraction and thermal analysis. In addition, the complex produces a 1.81-fold enhancement in apparent bioavailability compared to artemether.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / pharmacokinetics
  • Artemether
  • Artemisinins / chemistry*
  • Artemisinins / pharmacokinetics
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Chemistry, Pharmaceutical
  • Magnetic Resonance Spectroscopy
  • Rats
  • Solubility
  • X-Ray Diffraction
  • beta-Cyclodextrins / chemistry*

Substances

  • Antimalarials
  • Artemisinins
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Artemether