Improved Solubility and In Vitro Dissolution of Ibuprofen from Poloxamer Gel Using Eutectic Mixture with Menthol

Abstract

To improve the solubility and in vitro dissolution 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 study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were 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 4 parts of ibuprofen formed eutectic mixture with 6 parts of menthol. In the presence of poloxamer 188, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without poloxamer and that without menthol, respectively. 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. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Dissolution mechanism showed that the dissolution rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixture with menthol, which gave the improved solubility and dissolution of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.

A fundamental investigation into the effects of eutectic formation on transmembrane transport

“…It was proven to be highly effective when applied to mucosal surfaces but a clear mechanistic understanding of permeation was not described (Carrasco et al, 1993). More recently similar effects have been shown when ibuprofen was combined with terpenes (Stott et al, 1998), menthol (Yong et al, 2003) and methyl nicotinate (Woolfson et al, 2000) to form a eutectic. This resulted in an increase in its permeation through the skin.…”

Insights into the Nature of Eutectic and Deep Eutectic Mixtures

“…Terpenes are a class of natural compounds widely used in the pharmaceutical field and their interactions with drugs have been extensively evaluated since well before the advent of DES. Mixtures of borneol/menthol [20][21][22], and camphor/menthol [23,24], were proposed as vehicles for transdermal delivery [5] while mixtures of thymol with ibuprofen [25] or meloxicam [26] and of menthol with ibuprofen [7,25,27], testosterone [28], lidocaine [29], or ubiquinone [30] have been investigated as analgesic, antimicrobial and anti-inflammatory vehicles. Under the new DES perspective menthol-based eutectic mixtures with pyruvic, acetic, l-lactic and lauric acids were reported as hydrophobic, low viscosity, DES, and applied to the extraction of caffeine, tryptophan, isophthalic acid, and vanillin [31].…”

Microemulsions based on paeonol-menthol eutectic mixture for enhanced transdermal delivery: formulation development and in vitro evaluation

“…Among the eutectic mixtures, the pae:men 4:6 system showed the highest solubility of paeonol (593.3 ± 26.6 lg/ml), which was even higher than the solubility of pure paeonol itself (537.9 ± 42.3 lg/ml). Similarly, Yong et al (2003) observed that the solubility of ibuprofen in water increased as the ratio of menthol to ibuprofen increased from 0:10 to 4:6, and then decreased as the ratio increasing from 4:6 to 10:0. These results suggested that the improved solubility of paeonol might be contributed by the formation of eutectic mixture of paeonol with menthol in the aqueous solution.…”

“…Eutectic mixtures can be formed between excipients [borneol and menthol (Shen et al 2011)], between drug and excipient [Ibuprofen and menthol (Yong et al 2003)] or between drugs [lidocaine and prilocaine (Chun et al 2012)]. Each of them has proven to be effective in facilitating drug transport through the skin corneum.…”