Physicochemical determinants of incompatibility and instability in injectable drug solutions and admixtures

Several physicochemical conditions or phenomena most commonly causing incompatibility, instability or related difficulties in parenteral drug solutions and admixtures are reviewed. The following factors involved in chemical incompatibilities are reviewed: concentration, pH, acid-base character, reduction-oxidation, photolysis, epimerization, temperature, dextrose catalysis and hydrolysis. The following factors involved in visual incompatibilities are discussed: pH, acid-base character, solvent system, color change, complexation, adsorption and adherence, dissolution rate, salting-out and leaching, and foaming. Pharmacists may recognize, predict and avoid parenteral imcompatibilities based on their experience, an understanding of physicochemical principles and reference to pertinent publications.