Inclusion complexation of artemisinin with alpha-, beta-, and gamma-cyclodextrins.
The present study was conducted to investigate the inclusion complexation of artemisinin (ART) with natural cyclodextrins (CyD), namely alpha-, beta-, and gamma-CyDs with the aim of improving its solubility and dissolution rate. Complex formation in aqueous solution and solid state was studied by solubility analysis, dissolution, and thermal analysis. Solubility diagrams indicated that the complexation of ART and the three CyDs occurred at a molar ratio of 1:1, and showed a remarkable increase in ART solubility. Moreover, the thermodynamic parameters calculated by using the van't Hoff equation revealed that the complexation process was associated with negative enthalpy of formation and occurred spontaneously. The complexation capability of CyDs with ART increased in the order of alpha- < gamma- < beta-CyDs and could be ascribed to the structural compatibility between the molecular size of ART and the diameter of the CyD cavities. Dissolution profiles of the three complexes demonstrated an increased rate and extent of dissolution compared with those of their respective physical mixtures and a commercial preparation. In solid-state analysis, using differential scanning calorimetry, the gamma-CyD was capable of complexing the highest percentage of ART, followed by beta- and alpha-CyDs. The respective estimated percentage of ART complexed by the CyDs were 85%, 40%, and 12%.
Wong
J W
JW
School of Pharmaceutical Sciences, University of Science Malaysia, Minden, Penang, Malaysia.
Yuen
K H
KH
D037621:Artemisinins / Q000737:chemistry* / Q000378:metabolism; D003505:Cyclodextrins / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D012717:Sesquiterpenes / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins
D037621:Artemisinins; D003505:Cyclodextrins; D012717:Sesquiterpenes; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; C031327:artemisinin; C031215:betadex; C023792:gamma-cyclodextrin; C032613:alpha-cyclodextrin