Effect of self-association on rate of penicillin G degradation in concentrated aqueous solutions.

The apparent rate of degradation of penicillin G potassium micellar solutions of 500,000 units/ml, a concentration commonly encountered in vials reconstituted for storage in the refrigerator, was investigated and compared to that of nonmicellar solutions of 8000 units/ml at 25 degrees, ionic strength of 1.1 M, and pH range from 5.0 to 9.5. In the micellar solutions the apparent rate of the H+-catalyzed degradation was increased twofold but that of water- and OH minus-catalyzed hydrolysis was decreased two- to three-fold. Consequently, the pH-rate profile of the micellar solutions was shifted to higher pH values and the pH of minimum degradation was found to be at 7.0 compared to 6.5 for the nonmicellar solution of the same ionic strength. Compared at their respective pH-rate profile minima, micellar penicillin G is 2.5 times as stable as the nonmicellar solution under the conditions of constant pH and ionic strength.