Nasal formulations of ketorolac tromethamine: technological evaluation--bioavailability and tolerability in rabbits
Santus, G.; Rivolta, R.; Bottoni, G.; Testa, B.; Canali, S.; Peano, S.
Farmaco 48(12): 1709-1723
1993
ISSN/ISBN: 0014-827X PMID: 8135994 Document Number: 420651
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.