Enhanced oral bioavailability of ibuprofen in rats by poloxamer gel using poloxamer 188 and menthol.
To improve the oral bioavailability of poorly water-soluble ibuprofen 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 ibuprofen-loaded preparations 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 an 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, 1.2 mg/mL. The simultaneous addition of menthol and poloxamer 188 significantly improved the dissolution rates of ibuprofen from aqueous solution due to the ibuprofen solubility-improving effect of menthol in the presence of poloxamer. Furthermore, the ibuprofen-loaded preparation with menthol and poloxamer 188 gave significantly higher initial plasma concentrations, Cmax, and AUC of ibuprofen than did the preparation without menthol and poloxamer 188, indicating that the simultaneous addition of menthol and poloxamer 188 could improve the oral bioavailability of ibuprofen in rats. In modern pain management it is always desirable for the ibuprofen-loaded preparation with poloxamer 188 and menthol to show a rapid onset of action with a minimal phase of lag time to feel the decreased pain. From an industry point of view, it is more desirable for a formulation to be fast acting, easy to use, and cost effective. Thus, the ibuprofen-loaded preparation with poloxamer 188 and menthol was a more effective oral dosage form for poorly water-soluble ibuprofen.
Yong
Chul Soon
CS
College of Pharmacy, Yeungnam University, Gyongsan, South Korea.
Lee
Mi-Kyung
MK
Park
Young-Joon
YJ
Kong
Kyung-Hwan
KH
Xuan
Jing Ji
JJ
Kim
Ji-Hyun
JH
Kim
Jung-Ae
JA
Lyoo
Won Seok
WS
Han
Sung Soo
SS
Rhee
Jong-Dal
JD
Kim
Jong Oh
JO
Yang
Chae Ha
CH
Kim
Chong-Kook
CK
Choi
Han-Gon
HG
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D005782:Gels; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008610:Menthol / Q000008:administration & dosage* / Q000737:chemistry; D014677:Pharmaceutical Vehicles; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D014677:Pharmaceutical Vehicles; D020442:Poloxamer; D008610:Menthol; D007052:Ibuprofen