Physicochemical properties of binary organic cosolvent-water mixtures and their relationships to muscle damage following intramuscular injection.

Using an in vitro model for the assessment of muscle damage after intramuscular injection of pharmaceutical preparations, we examined the muscle damage caused by three series of binary cosolvent mixtures as functions of their dielectric constant, apparent pH, surface tension, and viscosity. The cosolvent systems we examined were propylene glycol-water, ethanol-water and polyethylene glycol 400-water mixtures. Muscle damage was measured by the in vitro release of creatine kinase from the isolated rat skeletal muscle. Although isolated correlations exist between muscle damage and the physicochemical properties of a particular series of cosolvent mixtures, no single property, or combination of those examined, can provide a unified prediction of the degree of muscle damage incurred. This result suggests that muscle damage caused by the organic cosolvents may arise from complex interactions of a given cosolvent with the biochemical processes occurring in the skeletal muscle rather than from the four physicochemical factors examined.