Study on absorption of indomethacin from sustained-release suppositories containing hydrogenated soybean lecithin in rabbits.
The absorption of indomethacin (IM) from suppositories containing hydrogenated soybean lecithin (HL) after rectal administration in rabbits was investigated with the aim of producing sustained-release suppositories. The suppositories were prepared by the fusion method with IM, HL and Witepsol H-15 (H-15). The IM release rate from the suppositories (IM 10 mg, HL 200 mg, total weight 1 g) was faster than that of the control suppositories without HL. The release of IM from the suppositories (IM 10 mg, HL 300 mg or 350 mg) showed slow-release profiles. In absorption studies in rabbits, sustained-plasma levels of IM were obtained when suppositories having an HL content of more than 300 mg were administered. The suppositories composed of Witepsol E-85 (melting point approximately 43 degrees C), 10 mg of IM, and 200 mg of HL, showed slow-release profiles in the release test, but did not show sustained plasma levels of IM in the absorption test. These results indicate that sustained-release suppositories able to release IM gradually from the surface of the suppositories can be obtained when HL, IM and H-15, whose melting point is lower than body temperature, are used in the preparation of the suppositories, provided that the HL content is high enough in relation to IM.
Nakajima
T
T
Takashima
Y
Y
Furuya
A
A
Ozawa
Y
Y
Kawashima
Y
Y
D000818:Animals; D003692:Delayed-Action Preparations; D005079:Excipients; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D010713:Phosphatidylcholines; D011817:Rabbits; D013025:Glycine max / Q000032:analysis; D013488:Suppositories
D003692:Delayed-Action Preparations; D005079:Excipients; D010713:Phosphatidylcholines; D013488:Suppositories; D007213:Indomethacin