Bioavailability of powdered inclusion compounds of nonsteroidal antiinflammatory drugs with .BETA.-cyclodextrin in rabbits and dogs.

Abstract

Freeze-dried inclusion compounds of nonsteroidal antiinflammatory drugs with .beta.-cyclodextrin were administered orally to rabbits and beagle dogs in comparison with simply freeze-dried drugs. The antiinflammatory drugs used were flufenamic acid, ibuprofen, ketoprofen and indomethacin. Freeze-dried inclusion compounds showed higher levels of blood concentration and cumulative urinary excretion compared with simply freeze-dried drugs, except for indomethacin. In general, freeze-dried inclusion compounds of drugs with .beta.-cyclodextrin showed a high dissolution rate and high bioavailability. As an exceptional case, no enhancement of the bioavailability was observed in rabbits for the inclusion compound of indomethacin compared with the simply freeze-dried drug. A double maxima phenomenon in blood concentration was observed in the cases of flufenamic acid and indomethacin.