Pluronic F-127 Gels as a Novel Vehicle for Rectal Administration of Indomethacin

Abstract

Polyoxyethylene-polyoxypropylene surface-active block copolymers (Pluronics®) were evaluated as a vehicle for rectal administration of indomethacin. The effects of the concentration of Pluronic F-127, temperature, and drug concentration on the drug release were studied by means of an in vitro release method using a cellulose membrane. With increasing concentration of Pluronic F-127 in the vehicle, a corresponding decrease in the apparent release rate of the drug occurred. The apparent release rate increased with increasing temperature from 20 to 44 °C. Increase in drug concentration increased the drug release rate. Indomethacin gel preparations made by dissolving the drug in Pluronic F-127 aqueous gel were administered rectally to rabbits and the drug plasma levels were compared with those after rectal administration of commercial suppositories. When a commercial suppository was given to rabbits, the plasma concentration reached the maximum level 30 min after administration. On the other hand, the gel preparation did not show a sharp peak of plasma concentration and produced a sustained plateau level of indomethacin from 15 min to 10 h without a lag time. Thus, it appeared that indomethacin preparations based on Pluronic F-127 aqueous gel may be practically useful as a rectal preparation with prolonged action and with reduced side effects. © 1986, The Pharmaceutical Society of Japan. All rights reserved.