Enhanced rectal bioavailability of ibuprofen in rats by poloxamer 188 and menthol.
To improve the bioavailability of poorly water-soluble ibuprofen in the rectum with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the poloxamer gels composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Release mechanism showed that the release rate of ibuprofen from the poloxamer gels without menthol was independent of the time but the drug might be released from the poloxamer gels with menthol by Fickian diffusion. Furthermore, the poloxamer gel with menthol (poloxamer/menthol/ibuprofen (15%/0.25%/2.5%)) gave significantly higher initial plasma concentrations, C(max) and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the poloxamer gel with poloxamer 188 and menthol was a more effective rectal dosage form for ibuprofen.
Yong
Chul Soon
CS
College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan 712-749, South Korea.
Yang
Chae Ha
CH
Rhee
Jong-Dal
JD
Lee
Beom-Jin
BJ
Kim
Dong-Chool
DC
Kim
Dae-Duk
DD
Kim
Chong-Kook
CK
Choi
Jun-Shik
JS
Choi
Han-Gon
HG
D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D004339:Drug Compounding; D005079:Excipients / Q000494:pharmacology; D005782:Gels; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D020442:Poloxamer / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013488:Suppositories; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D005782:Gels; D013488:Suppositories; D013501:Surface-Active Agents; D014867:Water; D020442:Poloxamer; D008610:Menthol; D007052:Ibuprofen