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.
Brandl
M
M
Pharmaceutical Research Syntex Research Palo Alto, CA 94304, USA.
Conley
D
D
Johnson
D
D
Johnson
D
D
D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D020910:Ketorolac; D020911:Ketorolac Tromethamine; D007700:Kinetics; D012995:Solubility; D012996:Solutions; D013237:Stereoisomerism; D013696:Temperature; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000737:chemistry; D014325:Tromethamine / Q000031:analogs & derivatives* / Q000737:chemistry
D012996:Solutions; D014325:Tromethamine; D020911:Ketorolac Tromethamine; D014046:Tolmetin; D020910:Ketorolac