Indomethacin sustained-release suppositories containing sugar ester.

Abstract

We prepared indomethacin (IM) sustained-release suppositories using sugar ester (SE) as an additive. The suppositories were prepared by the fusion method with IM, SE, and Witepsol H-15 (H-15) and their availabilities in vitro and in vivo were evaluated mainly by the drug release test and the absorption test in rabbits, respectively. The softening point of the suppositories increased with increasing SE content. In the release test with the Muranishi method, slow-release profiles were obtained when the SE content was more than 52.5%. The absorption of IM from these suppositories, however, was very little. In the other release test, e.g. immersion method with gauze, all of the suppositories with SE showed slow-release profiles, and the drug release rates clearly depended on the SE content. The drug was released from the suppositories by the following leaching-type mechanism proposed by Higuchi. The suppository with a 30% SE content showed a sustained-plasma level of IM, but the other suppositories did not. It was concluded that an appropriate content of SE (i.e. 30%) in the suppository base was required to obtain sustained-release because it reasonably regulated the infiltration of rectal fluid into the suppository and the mechanical strength of the suppository against disintegration.