Enhanced Oral Bioavailability of Ibuprofen in Rats by Poloxamer Gel Using Poloxamer 188 and Menthol

Abstract

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.

Targeted nanoparticle-based drug delivery and diagnosis

“…As an example, Yong et al (2005) investigated the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen. In the presence of poloxamer, the solutions abruptly increased in the solubility of ibuprofen.…”

Development of novel ibuprofen-loaded solid dispersion with improved bioavailability using aqueous solution

“…The mobile phase consisted of acetonitrile and phosphate buffer (pH 3.5) (4:6, volume ratio). The eluent was monitored at 220 nm with a flow rate of 1.2 mL/min Newa et al, 2007;Rasenack and Muller 2002 b;Yong et al, 2005).…”

“…The supernatant layer (0.4 mL) was evaporated under N 2 (g). The residue was reconstituted with 50 µL of mobile phase, and 20 µL of the resulting solution was analyzed by HPLC as mentioned above Yong et al, 2005).…”

“…However, the bioavailability of ibuprofen is relatively low after oral administration, since it is practically insoluble in water (Greenhalgh et al, 1999;Glowka, 2000). Various oral formulations of ibuprofen such as prodrug (Murtha and Ando, 1994), inclusion complex (Charoenchaitrakool et al, 2002;Ghorab and Adeyeye, 2001), microcapsule (Kachrimanis et al, 2000;, solid dispersion (Greenhalgh et al, 1999;Newa et al, 2007;Rasenack and Muller 2002 a) and formation of eutectic mixture (Yong et al, 2005) were developed to improve the solubility of ibuprofen.…”

Supercritical Antisolvent Versus Coevaporation— Preparation and Characterization of Solid Dispersions

“…Many methods have been proposed in the literature to overcome such difficulties, including micronization (Miranda & Jaeger, 1998), surface modification (Cassidy et al, 1998), formation of complexes (Szente & Szejtli, 1999;Perrut et al, 2002;Lochard et al, 2004), eutectic mixtures (Yong et al, 2005), solvates, solid solutions and solid dispersions (Leuner & Dressman, 2000). In solid solutions and solid dispersions drug molecules or very fine drug crystals are dispersed in a biocompatible matrix.…”