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In vivo and in vitro release of indomethacin from water-soluble and fatty base suppositories.

The plasma concentration of indomethacin was measured after the rectal administration of water-soluble and fatty base suppositories in rats. The results were compared with the in vitro indomethacin release from suppositories determined by Paddle method using three different types of membranes: cellulose membrane, artificial sausage membrane and natural sausage membrane. The plasma concentrations of indomethacin during the first 4h after the rectal administration were higher in rats that received water-soluble base suppositories than in those that received fatty base types. When either a cellulose membrane or an artificial sausage membrane of cow protein was used in the Paddle method, the amount of indomethacin released from fatty base suppositories was significantly higher than that from water-soluble base ones. However, the results were reversed when a natural sausage membrane of pig colon was used. The discrepancy in the in vitro experiments using water-soluble base suppositories seemed to be due to the difference of pore size of membrane used. Careful consideration should be given to the membrane used in the Paddle method especially when this method is employed to examine the release of poorly soluble drugs like indomethacin in both water-soluble and fatty base suppositories.