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

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...

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Main Authors: Ansari, M., Batty, Kevin, Iqbal, Ijaz, Sunderland, Vivian
Format: Journal Article
Published: Pharmaceutical Society of Korea 2011
Online Access:http://hdl.handle.net/20.500.11937/43367
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author Ansari, M.
Batty, Kevin
Iqbal, Ijaz
Sunderland, Vivian
author_facet Ansari, M.
Batty, Kevin
Iqbal, Ijaz
Sunderland, Vivian
author_sort Ansari, M.
building Curtin Institutional Repository
collection Online Access
description 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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spelling curtin-20.500.11937-433672017-09-13T16:00:44Z Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes Ansari, M. Batty, Kevin Iqbal, Ijaz Sunderland, Vivian 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. 2011 Journal Article http://hdl.handle.net/20.500.11937/43367 10.1007/s12272-011-0509-1 Pharmaceutical Society of Korea restricted
spellingShingle Ansari, M.
Batty, Kevin
Iqbal, Ijaz
Sunderland, Vivian
Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes
title Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes
title_full Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes
title_fullStr Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes
title_full_unstemmed Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes
title_short Improving the Solubility and Bioavailability of Dihydroartemisinin by Solid Dispersions and Inclusion Complexes
title_sort improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes
url http://hdl.handle.net/20.500.11937/43367