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• W817647524 abstract "Artesunate, ART, is an antimalarial drug which is the only soluble artemisinin available on the market. ART has a low stability in aqueous solution. The degradation rate of ART in aqueous solution in a range of pH values (2.00-10.50) and selected IV fluids at 37 °C was studied. The temperature dependence was also investigated. High-performance liquid chromatography, HPLC, with detection at 210 nm was employed. There were significant effects on the rate degradation of ART according to the pH value employed and temperature. Shelf-lives of ART were 2.5, 1.2 and 1.0 h when reconstituted at 0.6 mg mL-1 in Hartman’s solution, 0.9% normal saline, and 5% glucose IV fluid at 37 °C respectively. The pH-rate profile demonstrated three general regions: decreased rate with pH fall to pH 7.50 followed by an increased rate. There was a combination of specific acid-base and carboxylate anion catalysis. Buffers may have a small effect on the degradation rates. The effect of ionic strength was slightly significant on the rat degradation of ART. A comparison in the rate degradation of ART with HPLC and LC-MS showed no significant difference in measured degradation rates.The effect of inclusion complexes of ART with hydroxypropyl-s-cyclodextrin (HPs- CD) at selected pH values on the phase solubility profile and stability of ART in aqueous solution was studied. The phase solubility profile of the complex was classified as AL- type, indicating the formation of a 1:1 stoichiometric inclusion complex. A complex of ART with HP-s-CD (272 mg mL-1) showed a 25-fold increase in solubility compared to ART at pH 3.00. Lineweaver-Burk plots were used to calculate the stability constants of the inclusion complexes (Kst) as well as the rate constants for degradation of the free and complexed drug. The stability constants Kst of the inclusion complexes were 83, 73 and 60 M-1 at pH 6.00, 7.00 and 8.00 respectively.The activation energies (Ea) were obtained from Arrhenius plots of degradation rate constants in the presence and absence of HP-s-CD. The thermodynamic parameters of activation enthalpy and entropy were obtained from Eyring Equation. The activation energies in the absence and presence of HP-s-CD were 93.4 and 95.8 Kjmol-1 respectively. The shelf-life of ART in the presence of HP-s-CD was increased five-fold. The shelf-life of ART at the pH minimum (pH 6.50) was 10.6 h. Then it was improved in the presence of 108 mg mL-1 HP-s-CD to 46 h." @default.
• W817647524 created "2016-06-24" @default.
• W817647524 creator A5032615256 @default.
• W817647524 date "2011-01-01" @default.
• W817647524 modified "2023-09-23" @default.
• W817647524 title "Degradation of Artesunate in Aqueous Solution" @default.
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