Enhanced absorption of indomethacin after oral or rectal administration of a self-emulsifying system containing indomethacin to rats.
A self-emulsifying system (SES), a mixture of an oil and a surfactant which forms an oil-in-water emulsion, is expected to improve the in vitro drug dissolution and enhance the in vivo drug absorption. In this study, a poorly water-soluble drug, indomethacin (IDM) was incorporated into the SES to increase bioavailability. The SES with 30% of Tween 85 and 70% of ethyl oleate, EO (w/w) was selected as an optimized formulation (high drug loading, low surfactant concentration, and small particle size). After an oral administration of the SES containing IDM and IDM suspension, (IDM was suspended in methyl cellulose), 22.5 mg/kg as IDM, to rats, the area under the plasma concentration-time curve from time zero to the last measured time in plasma, 12 h (AUC(0-12 h)) was significantly greater (57% increase) in the SES, suggesting that oral absorption of IDM increased significantly by the SES. After a rectal administration of gelatin hollow type suppositories, filled with the SES containing IDM and IDM powder physically mixed with the SES, 22. 5 mg/kg, to rats, the AUC(0-12 h) also increased significantly (41% increase) by the SES, suggesting that rectal absorption of IDM also increased significantly by the SES.
Kim
J Y
JY
Department of Pharmaceutics, College of Pharmacy, Ewha Womans University, 11-1 Daehyon-Dong, Sodaemun-Ku, Seoul, South Korea.
Ku
Y S
YS
D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D016503:Drug Delivery Systems; D004655:Emulsions; D007213:Indomethacin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D009829:Oleic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011136:Polysorbates / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013488:Suppositories; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014783:Viscosity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D009829:Oleic Acids; D011136:Polysorbates; D013488:Suppositories; D013501:Surface-Active Agents; D007213:Indomethacin; C033180:ethyl oleate