Improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes

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.

Dihydroartemisinin-Loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

“…As shown in Figure 1F, the cumulative release of ART was about 45.5% and DHA was about 42.9% over 24 h, which confirmed that the capacities of MNP to hold ART and DHA in physiological environment were similar. Actually, the solubility of DHA was slightly lower than ART, so during the first 2 h of the release process, ART exhibited a distinct rapid release behavior, which DHA didn't (Wang et al, 2007;Ansari et al, 2011). In addition, the cumulative release of AS reached 72.1% over 24 h, indicating that AS was more hydrophilic than ART and DHA, which was consistent with the reported work (Xu R.J. et al, 2019).…”

Inclusion of terpenes in cyclodextrins: Preparation, characterization and pharmacological approaches

“…Consequently, this enhanced the therapeutic effectiveness of artemisinin (Wong & Yuen, 2003b). These results were also played out in others studies using the derivatives of dihydroartemisinin (DHA), which in a complexation with HP-β-CD, equally improved the pharmacokinetic parameters when compared with DHA alone (Ansari, Batty, Iqbal & Sunderland, 2011). Artesunate in β-CD conjugates with a cytotoxicity against three types of human colon cancer cell lines (Jiang et al, 2014).…”

Dihydroartemisinin-loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

“…As shown in Figure 1F, the cumulative release of ART was about 45.5 % and DHA was 226 about 42.9 % over 24 h, which confirmed that the capacities of MNP to hold ART and DHA in 227 physiological environment were similar. Actually, the solubility of DHA was slightly lower than ART, 228 so during the first 2 hours of the release process, ART exhibited a distinct rapid release behavior, which 229 DHA didn't (Wang et al, 2007;Ansari et al, 2011). In addition, the cumulative release of AS reached 230 72.1 % over 24 h, indicating that AS was more hydrophilic than ART and DHA, which was consistent 231…”