Dipolar motions and ionic conduction in an ibuprofen derived ionic liquid

Abstract

It was demonstrated that the combination of the almost water insoluble active pharmaceutical ingredient (API) ibuprofen with the biocompatible 1-ethanol-3-methylimidazolium [C2OHMIM] cation of an ionic liquid (IL) leads to a highly water miscible IL-API with a solubility increased by around 5 orders of magnitude. Its phase transformations, as crystallization and glass transition, are highly sensitive to the water content, the latter shifting to higher temperatures upon dehydration. By dielectric relaxation spectroscopy the dynamical behavior of anhydrous [C2OHMIM][Ibu] and with 18.5 and 3% of water content (w/w) was probed from well below the calorimetric glass transition (Tg) up to the liquid state. Multiple reorientational dipolar processes were detected which become strongly affected by conductivity and electrode polarization near above Tg. Therefore [C2OHMIM][Ibu] exhibits mixed behavior of a conventional molecular glass former and an ionic conductor being analysed in this work through conductivity, electrical modulus and complex permittivity. The dominant process, σα-process, originates by a coupling between both charge transport and dipolar mechanisms. The structural relaxation times were derived from permittivity analysis and confirmed by temperature modulated differential scanning calorimetry. The temperature dependence of the β-secondary relaxation is coherent with a Johari-Goldstein (βJG) process as detected in conventional glass formers.

Ionic Liquids and Salts from Ibuprofen as Promising Innovative Formulations of an Old Drug

“…CationAppearance [30] Pale-yellow solid -1 To each meltings tep there is ac rystallization phenomenon in the consequentc ooling step, which is consistent with the presence of differentpolymorphs. All RTILs display vitreous transitiont emperatures (T g )b etween À29.1 and À24.8 8C, while no crystallization peaks were observedd uring the heating/cooling cycles.…”

“…Furthermore, the polymorphism of ag iven API can be decreased to ac ertaine xtent or even eliminated (e.g.,b yb ecoming liquid at room temperature), tackling one of the most important issues in the pharmaceutical industry responsible for limitations in ag iven drug's solubility and dosage. [28][29][30] Hence, herein we report the synthesis of eight new ILs and organic salts from ibuprofen, plus one already reported, [30] in quantitative yields by deprotonation of the carboxylic acid from ibuprofen by the hydroxide salt of the cations. Scheme 1d epicts the methodology and the structure of the imidazolium, ammonium, and pyridiniumc ations used.The selected cations were 1-ethyl-3-methylimidazoliumt etraethylammonium [TEA],c holine [Cholin],2 -hydroxy-N-(2-hydroxyethyl)-N,N-dimethylethanaminium[ N 1,1,2OH,2OH ], N-ethyl-2-hydroxy-N,Ndimethylpropan-1-aminium [N 1,1,2,2OH1 ], and cetylpyridinium [C 16 Pyr].The most straightforward methodology for the preparation of ILs consists of the metathesis reaction of an organic cation halide with an alkaline salt, in which the desired product must be separated from the halide salt by-product by precipitation and filtrationo ft he later.…”

“…Furthermore, the polymorphism of ag iven API can be decreased to ac ertaine xtent or even eliminated (e.g.,b yb ecoming liquid at room temperature), tackling one of the most important issues in the pharmaceutical industry responsible for limitations in ag iven drug's solubility and dosage. [28][29][30] Hence, herein we report the synthesis of eight new ILs and organic salts from ibuprofen, plus one already reported, [30] in quantitative yields by deprotonation of the carboxylic acid from ibuprofen by the hydroxide salt of the cations. Scheme 1d epicts the methodology and the structure of the imidazolium, ammonium, and pyridiniumc ations used.…”

“…The selected cations were 1-ethyl-3-methylimidazolium [EMIM], 1-hydroxy-ethyl-3-methylimidazolium [C 2 OHMIM] [30] ,1 -…”

Ionic and conformational mobility in poly(vinylidene fluoride)/ionic liquid blends: Dielectric and electrical conductivity behavior

“…The 0 factor for samples with IL amount is of the order > 10 -13 s, as the typical values for non-cooperative Debye process originated by local orientational fluctuations [55].…”