Biol. Pharm. Bull. 28(8) 1480—1484 (2005)

cancer pain. The oral route is the first choice in administering medication to relieve it, but clinical experience has shown that alternative routes of administration should be employed for patients suffering from nausea and vomiting. Furthermore, as morphine is subjected to the extensive first-pass metabolism after oral administration, the rectal administration of morphine, which can partially avoid the hepatic first-pass metabolism, leads to higher bioavailability, compared with the oral dosing. Therefore, the rectal route is very important for the management of severe pain by morphine. Morphine suppository preparations used clinically are not of the sustained-release type, so more than 3 doses per day are required to maintain the analgesic effect due to the rapid elimination of morphine. Therefore, controlled-release dosage forms are considered to be particularly appropriate for morphine. Sustained-release suppositories of morphine have been investigated, and the release of morphine was controlled by hydrogel, modified suppository base such as light anhydrous silicic acid (Aerosil) or alginic acid. In another case, a controlled-release morphine tablet was investigated for rectal use. Polyglycerol ester of fatty acid (PGEF) is a solid fat and has excellent characteristics as an additive of controlled-release suppository. PGEFs have a well affinity with the fatty suppository bases, and the matrix bases can be homogeneously prepared by adding PGEFs to suppository bases, which may provide a stable controlled-release system. In the present study, a novel type of controlled-release suppositories has been developed for morphine by using PGEF as an additive of suppository. Physicochemical characteristics of the suppositories and the release properties of morphine from the suppositories were evaluated in an in vitro study. Furthermore, in vivo absorption studies were performed in beagle dogs.