Racemization of ketorolac in aqueous solution.

The racemization of ketorolac was studied in aqueous buffered solution at 25 and 80 degrees C and analyzed in detail with respect to the catalytic species in solution. The reaction has a U shaped pH rate profile at 80 degrees C with the pH of maximum stability occurring in the region of pH 3.0-7.5. A T90 value of 8 months was observed for a 1.5% (R)-ketorolac tromethamine solution at pH 7.4 and 25 degrees C. Additionally, the data shows that alternative salt forms are necessary in order to prepare a stable single isomer formulation. Alternative buffers, in particular phosphate buffer, provide formulations exhibiting a T90 greater than 2 years.