Indomethacin sustained-release suppositories containing sugar ester in polyethylene glycol base.
Indomethacin (IM) sustained-release suppositories were prepared by the fusion method using sugar ester and polyethylene glycol 4000 (PEG). The suppositories were evaluated by in vitro release testing, X-ray analysis and in vivo absorption testing in rabbits. X-ray analysis showed that IM was amorphous in PEG-base suppositories. In a release test, slow-release was obtained when the sugar ester content of a suppository was 60%. The IM plasma level following the administration of the suppository was well sustained in the absorption test. The main slow-release mechanism is considered to be the release of IM from the matrix composed of sugar ester and PEG, which is represented by the Higuchi equation. A good correlation between the release test and the absorption test was obtained. It is considered that the amorphous state of IM in this type of sustained-release suppository would enhance the release and absorption of IM in the rectum of the rabbit, whose rectal fluid volume is small.
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
T
T
Nakajima
Y
Y
Takashima
A
A
Furuya
Y
Y
Ozawa
Y
Y
Kawashima
D000818:Animals; D003692:Delayed-Action Preparations; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011092:Polyethylene Glycols; D011817:Rabbits; D013488:Suppositories
D003692:Delayed-Action Preparations; D013488:Suppositories; D011092:Polyethylene Glycols; D007213:Indomethacin