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    Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes

    Access Status
    Fulltext not available
    Authors
    Ansari, M.
    Batty, Kevin
    Iqbal, Ijaz
    Sunderland, Vivian
    Date
    2011
    Type
    Journal Article
    
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    Citation
    Ansari, Muhammad and Batty, Kevin and Iqbal, Ijaz and Sunderland, Vivian. 2011. Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes. Archives of Pharmacal Research 34(5): pp. 757-765.
    Source Title
    Archives of Pharmacal Research
    DOI
    10.1007/s12272-011-0509-1
    ISSN
    02536269
    School
    School of Pharmacy
    URI
    http://hdl.handle.net/20.500.11937/43367
    Collection
    • Curtin Research Publications
    Abstract

    Dihydroartemisinin (DHA) is a poorly water-soluble drug that displays low bioavailability after oral administration. Attempts have been made to improve the solubility of DHA. Yet, no information is available concerning improved bioavailability. This study aimed to improve the water solubility of DHA by two systems: solid dispersions with polyvinylpyrrolidone (PVPK30, PVPK25, PVPK15) and inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD), as well as improving the bioavailability of both systems. The phase transition of DHA with hydrophilic polymers was evaluated by X-ray diffraction (XRD) and differential scanning calorimetery (DSC). DHA became amorphous in DHA-HPβCD complexes and showed more amorphous behavior in XRD analyses with rise in molecular weight of PVP. Melting onset temperature of DHA decreased, while DSC thermograms revealed the peak area and enhanced enthalpy change (DH) in solid dispersions as well as inclusion complexes. DHA solubility was enhanced 84-fold in DHA-HPβCD complexes and 50-times in DHA-PVPK30. The improved solubility using the four polymers was in the following order: HPβCD > PVPK30 > PVPK25 > PVPK15. Values of area under curve (AUC) and half life (t(1/2)) of DHA-PVPK30 were highest followed by DHA-HPβCD, DHA-PVPK15 and DHA-PVPK25. V(d)/f of DHA-PVPK30 was 7-fold. DHA-HPβCD, DHA-PVPK15 and DHA-PVPK25 showed significantly different pharmacokinetic parameters compared with DHA solutions. The 95% confidence interval was meaningful in AUC and t(1/2). Pharmacokinetic parameters revealed that all four-test preparations were significantly more bioavailable than DHA alone.

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