Pharmacokinetics of Sulfisoxazole Solid Dispersions in Rabbis

Abstract

The approach of solid dispersion was found useful for optimizing the pharmacokinetics of sulfisoxazole in Rabbits. This was illustrated on the example of bicomponent solid dispersions containing water-soluble, urea and pvp 25000, and water insoluble, DCA and GMS, carriers. The effect of the type and concentration of the inert carrier was investigated and found to influence the pharmacokinetic parameters studied to different extents. The multicomponent (Tri and quaternary) solid dispersions implied different effects on the pharmacokinetics of sulfisoxazole according to the nature and the proportion of the carrier used. Dispersing sulfisoxazole in the solid state in innert carriers such as GMS, DCA, urea and PVP was shown to influence significantly the dissolution rate of the drug to different extents. Dispersion of sulfisoxazole in soluble carriers resulted in significant enhancement of the dissolution rate whatever the equipment used. Correlation of sulfisoxazole in-vitro dissolution rate parameters, D.E. and t_75%, to the pharmacokinetic parameters revealed no or very poor correlation.However, the t_75% parameter by the USP disintegration tester may be considered to exhibit the most reasonable correlation to the pharmacokinetic parameter K_e.