Physicochemical compatibility and stability of nebulizable drug admixtures containing dornase alfa and tobramycin

Abstract

The objective of this in-vitro study was to determine whether admixtures of the inhalation solutions Pulmozyme® (Dornase alfa) and either Bramitob® or Tobi® (both containing Tobramycin) are physicochemically compatible and to analyze the aerodynamic parameters of these admixtures. After mixing, test solutions were stored at room temperature and under ambient light conditions over a period of 24 h. Tobramycin concentrations were determined by using a fluorescence immunoassay. Stability of dornase alfa was determined by size-exclusion high performance liquid chromatography, ultraviolet spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis and tentacle strong cation-exchange chromatography. In addition, pH values and osmolality of the admixtures were measured and test solutions were visually examined for any changes up to 24 h. Aerosols of Pulmozyme®/Bramitob® or Pulmozyme®/TOBI® admixtures were generated with the PARI eFlow® rapid and aerodynamic particle sizing was performed via cascade impaction with the Next Generation Pharmaceutical Impactor. The stability tests revealed that neither the stability of tobramycin nor the stability of dornase alfa was affected by mixing the inhalation products. Cascade impaction showed no relevant changes in particle size distribution, Mass Median Aerodynamic Diameter, Geometric Standard Deviation and Fine Particle Fraction in comparison to aerodynamic parameters of the unmixed solutions. Thus, admixtures of Pulmozyme® and either Bramitob® or TOBI® can be designated as compatible for a 24 h period and simultaneous inhalation is feasible.