Stabilization of Bitolterol by the Use of Mixed Solvent Systems

Abstract

Analytical methods using thin-layer and high pressure liquid chromatographic techniques were developed and utilized for measuring decreases in bitolterol concentrations as a function of time. Pseudo first-order hydrolysis rate constants were determined and shown to be strongly dependent upon pH and solvent polarity for this catecholamine diester. The activation energy was calculated as 18 kilocalories per mole for bitolterol in aqueous buffer solution both with or without 25% alcohol. Large reductions in rate constants as a function of dielectric constant were demonstrated and illustrate that solvent polarity effects may be important for drug stabilization.