Artemether/hydroxypropyl-beta-cyclodextrin host-guest system: characterization, phase-solubility and inclusion mode.
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.
Yang
Bo
B
School of Chemistry, Key Laboratory of Medicinal Chemistry for Natural Resource (Ministry of Education), Yunnan University, Kunming 650091, PR China.
Lin
Jun
J
Chen
Yong
Y
Liu
Yu
Y
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000493:pharmacokinetics; D000077549:Artemether; D037621:Artemisinins / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D012995:Solubility; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000962:Antimalarials; D037621:Artemisinins; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077549:Artemether