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.

Comparison of physicochemical properties of suppositories containing starch hydrolysates

“…Sustained release suppositories are preferable to conventional suppositories because they reduce the frequency of drug administration. Several approaches have been performed to prepare the controlled release suppositories by using various additives such as lecithin (Nishihata et al, 1985), sucrose fatty ester (Nakajima et al, 1990), carboxyvinyl polymer (Azechi et al, 2000, Yahagi et al, 2000) and various hydrogel formulations (Morimoto et al, 1989, Miyazaki et al, 1998).…”

Studies on Uniformity of the Active Ingredients in Acetaminophen Suppositories Re-solidified after Melting under High Temperature Conditions

“…Some reports have verified the role of additives in controlling sustained active ingredient dissolution from the base, including: solid fats such as the polyglycerol ester of fatty acids, 13) lecithin, 16) sucrose fatty acid ester, 17) carboxyvinyl polymer, 18,19) xyloglucan gels, 20) and polyvinyl alcohol hydrogel. 21) However, the only inactive pharmaceutical ingredient in the five products (Table 1; SUP-A, SUP-B, SUP-C, SUP-D andSUP-E)ishardfat.InSUP-FandSUP-G,whichhavelow dissolution profiles, SiO 2 and MCT were added in addition to the hard fat, but only the number of carbon atoms in the fatty acid was less (Table 1).…”

Symptom control in cancer patients: the clinical pharmacology and therapeutic role of suppositories and rectal suspensions

“…Peak plasma concentrations occur within 20 min with rectal solutions, 40 min with administration by mouth, and 60 min with rectal suppositories [76]. A sustained-release suppository can be produced by adding sugar esters to a lipophilic (Witepsol H-15) base [111]. Postoperative indomethacin suppositories (100 mg dosed every 12 h) reduce morphine consumption postoperatively by 38% compared with a placebo control [142].…”