Approaches for improving the stability of ketorolac in powder blends.
Methods for improving the stability of ketorolac powder blends under elevated humidity and temperature conditions were investigated. The approaches that were examined for potentially increasing the stability of ketorolac were varying the ketorolac salt form, altering the excipient ratios, and adding antioxidants or pH modifiers to the formulation. The ketorolac powder blends were stored for 3 months at 75% relative humidity (RH) and 40, 50, and 60 degrees C. The results showed that the salt form of ketorolac had a large impact on stability after 3 months of storage at 50 degrees C/75% RH. The calcium salt powder blend and the free acid powder blend exhibited only 0.2% and 0.5% drug loss, respectively, whereas the tromethamine salt powder blend showed a 10.2% drug loss. Varying the ratios of lactose, microcrystalline cellulose, and croscarmellose sodium in the powder blends of ketorolac tromethamine showed that croscarmellose sodium and microcrystalline cellulose destabilized ketorolac. Addition of propyl gallate (1% w:w) to ketorolac tromethamine powder blends increased the stability of the ketorolac significantly. Addition of pH modifiers caused a modest improvement in the stability of ketorolac.
Brandl
M
M
Pharmaceutical Research, Syntex Research, Palo Alto, CA 94304, USA.
Magill
A
A
Rudraraju
V
V
Gordon
M S
MS
D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D006863:Hydrogen-Ion Concentration; D020911:Ketorolac Tromethamine; D007785:Lactose / Q000737:chemistry; D010592:Pharmaceutic Aids / Q000737:chemistry; D011208:Powders; D013696:Temperature; D014046:Tolmetin / Q000031:analogs & derivatives / Q000737:chemistry; D014325:Tromethamine / Q000031:analogs & derivatives / Q000737:chemistry
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010592:Pharmaceutic Aids; D011208:Powders; D014325:Tromethamine; D020911:Ketorolac Tromethamine; D002482:Cellulose; D014046:Tolmetin; D007785:Lactose; D002266:Carboxymethylcellulose Sodium