Lysis of human red blood cells 2: effect of contact time on cosolvent induced hemolysis

The degree of hemolysis induced by several cosolvent formulations is evaluated at various contact times using the dynamic in vitro method developed by Krzyzaniak (Krzyzanik, J.F., Raymond, D.M. and Yalkowsky, S.H., Lysis of Human Red Blood Cells 1: Effect of Contact Time on Water Induced Hemolysis. PDA J. Pharm. Sci. & Tech., 50 (1996) 223–226). Hemolysis is shown to increase with cosolvent concentration and to be sigmoidally related to the logarithm of the formulation:blood contact time. With this information, a physiologically realistic in vitro method with a formulation:blood ratio of 0.1 and a contact time of 1 s has been developed and used to estimate the amount of hemolysis occurring after an intravenous injection of some commonly used cosolvent formulations.