Nasal formulations of ketorolac tromethamine: technological evaluation--bioavailability and tolerability in rabbits.
This paper describes the development of a novel formulation of the powerful non narcotic analgesic ketorolac tromethamine. This drug is given orally three to four times/day to deliver a total of 30 to 60 mg of drug. Higher doses cannot be given orally because of gastrointestinal side effects and intramuscular injections, three times/day must then be used. The need for injections limits the drug to a clinical setting. Nasal delivery offers a method of achieving the high blood levels of repeated intramuscular injections in a formulation that can be easily applied by the patients. Four formulations were evaluated in "in vitro" and "in vivo" rabbit tests. The best formulation consisted of a 5% solution of ketorolac tromethamine containing 0.3% sodium glycocolate as a known mucosal drug absorption enhancer. Ketorolac applied in this way had a bioavailability greater than 80%. The controlled release nature of nasal delivery also doubled the drug's apparent half life. The drug formulation was stable in three-months stability tests and produced minimal nasal irritation.
Santus
G
G
Recordati SpA, Milano, Italy.
Rivolta
R
R
Bottoni
G
G
Testa
B
B
Canali
S
S
Peano
S
S
D000281:Administration, Intranasal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D004355:Drug Stability; D006207:Half-Life; D007275:Injections, Intravenous; D020911:Ketorolac Tromethamine; D008297:Male; D009296:Nasal Cavity / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D014046:Tolmetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D014325:Tromethamine / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D014325:Tromethamine; D020911:Ketorolac Tromethamine; D014046:Tolmetin