Physicochemical properties of the novel heteropolyanion antiviral hexapotassium-alpha-vanado-11-tungstoborate (DuP 925).
Hexapotassium-alpha-vanado-11-tungstoborate (DuP 925) is a yellow irregular-shaped crystalline powder. The DSC thermogram indicates that decomposition begins to occur above 250 degrees C. The compound exhibits a volatile loss of 3.7% by thermogravimetric analysis. The drug substance adsorbs water reaching a 7.1% volatile loss after 3 weeks at 85% relative humidity. The solubility of DuP 925 in water is high (1.6 g/ml at pH 4.8). Changes in pH have a negligible effect on the solubility with values of 1.3 g/ml in 0.1 N HCl and 1.4 g/ml in 0.1 N NaOH. The solubility is minimally affected by changes in sodium ion concentration. The compound ion pairs with tetrabutyl-ammonium ions at 1:2 and 1:6 ratios, with the 1:6 ion pair having an affinity over six orders of magnitude greater than that of the 1:2 ion pair. The degradation of DuP 925 in solution follows apparent first-order kinetics over the pH range of 0.6 to 12.6 at 80 degrees C. Citrate, EDTA, and phosphate buffers are catalytic at the pH minimum, with citrate and EDTA being stronger catalysts than phosphate. Acetate buffers appear to have negligible catalytic effects at pH 4 to 5. The degradation proceeds through the formation of the symmetrical dodecatungstoborate [BW12O40]-5. In acid, the dodecatungstoborate is stable, while in base it degrades further. Increasing the ionic strength has a catalytic effect on the degradation of DuP 925, while changes in the initial concentration of DuP 925 have a negligible effect on the stability. The pH-rate profile indicates a pH minimum of approximately 3.
Maurin
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MB
Pharmacy R&D, Du Pont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0336.
Vickery
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RD
Bryant
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WM
Hussain
M A
MA
D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D012995:Solubility; D013818:Thermogravimetry; D014414:Tungsten / Q000032:analysis*; D017973:Tungsten Compounds; D014638:Vanadates / Q000032:analysis*
D017973:Tungsten Compounds; D014638:Vanadates; C076004:DuP 925; D014414:Tungsten