Enhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropes

Abstract

The therapeutic effectiveness of a drug largely depends on its bioavailability, and thus ultimately on its aqueous solubility. Hydrotropes are compounds able to enhance the solubility of hydrophobic substances in aqueous media and therefore are extensively used in the formulation of drugs and personal care products. Recently, some ionic liquids were shown to display a strong ability to enhance the solubility of biomolecules through hydrotropy. In this work, the impact of the ionic liquid chemical structures and their concentration on the solubility of ibuprofen was evaluated and compared with the performance of conventional hydrotropes. The results obtained clearly evidence the exceptional capacity of ionic liquids to enhance the solubility of ibuprofen. [CCim][SCN] and [CCim][N(CN)] seem to be the most promising ionic liquids for ibuprofen solubilisation, where an increase in the solubility of 60- and 120-fold was observed with ionic liquid concentrations of circa 1 mol kg, respectively. Dynamic light scattering and molecular dynamics simulations were used to investigate the mechanism of the IL-mediated drug solubility and the results obtained indicate that the structure of aqueous solutions of ionic liquids and the role it plays in the formation of ionic liquid-drug aggregates is the mechanism driving the hydrotropic dissolution.

How imidazolium‐based ionic liquids solubilize the poorly soluble ibuprofen? A theoretical study

“…Such result indicates that the polarity of cations plays an important role for ibuprofen dissolution. Recently, Coutinho et al found that ibuprofen showed a higher solubility in the imidazolium‐based ILs than that in the pyridinium‐, piperidinium‐, pyrrolidinium‐, tetrabutylammonium‐, and tetrabutylphosphonium‐based ILs. The obvious difference actually came from imidazolium cation with higher polarity due to a sp2 nitrogen heteroatom in the imidazolium rings that induce a dipolar character .…”

“…Recently, various computational methods have been used to investigate the solute‐solvent interaction at the molecular level in order to understand the major factors contributing to the favorable solvation of drugs in various ILs . For example, Paluch et al used molecular dynamics (MD) simulations to study the solvation mechanism of acetaminophen in 21 imidazolium‐based ILs.…”

“…In addition, Coutinho et al illustrated that the solvation mechanism of vanillin was observed to be most likely the formation of π–π interactions between vanillin and cations. However, another MD study performed by them pointed out that π–π interactions between ibuprofen and cations were not the dominant driving force for the mechanism of the increased solubility of ibuprofen . According to above studies, the underlying solvation mechanism of drugs in imidazolium‐based ILs is still unclear and controversial.…”

“…Recently, various computational methods have been used to investigate the solute-solvent interaction at the molecular level in order to understand the major factors contributing to the favorable solvation of drugs in various ILs. [35][36][37][38][39][40][41][42][43][44] For example, Paluch et al 38 used molecular dynamics (MD) simulations to study the solvation mechanism of acetaminophen in 21 imidazolium-based ILs. They found that the strong solvation of acetaminophen in ILs was dominated by the strong HB interaction between acetaminophen and anions, while the cations played a minor role.…”

“…However, another MD study performed by them pointed out that π-π interactions between ibuprofen and cations were not the dominant driving force for the mechanism of the increased solubility of ibuprofen. 42 According to above studies, the underlying solvation mechanism of drugs in imidazolium-based ILs is still unclear and controversial. Clearly, much more simulation studies are necessary to expose the solvation structure details of drugs in imidazolium-based ILs as well as the role of cations and anions in the interaction with drugs during the solvation process, including the π-π interactions, van der Waals interaction, electrostatic interaction and HB interactions.…”