New ibuprofen derivatives were made via conjugation with L-valine alkyl esters (ValOR), where R was changed from an ethyl to a hexyl group. The ionic structure was confirmed using NMR and FTIR. Specific rotation, solubility in commonly used solvents, thermal properties including phase transitions temperatures, and thermal stability were also determined. The ionic structure with a protonated amine group on an L-valine ester and melting points below 100 °C allowed inclusion of these ibuprofen derivatives into the pharmaceutically active protic ionic liquids. The ibuprofen salt solubility in deionised water and two buffer solutions at pH 5.4 and 7.4 were established and compared with the parent acid solubility. The octanol/water (buffer) partition coefficient, permeation through porcine skin, and accumulation in the skin were also measured. Ibuprofen pairing with L-valine alkyl esters [ValOR][IBU], caused higher solubility and a greater drug molecule absorption through biological membranes. log P was lower for ibuprofen salts than for the acid and it increased with a longer L-valine ester cation alkyl chain. In vitro porcine skin tests showed that ibuprofen salts with a propyl or isopropyl ester in L-valine are particularly relevant for topical application. They provide transport for ibuprofen through the skin at much higher rate than the unmodified acid and a higher permeated ibuprofen concentration, which can improve efficacy. Thus, synthesised ibuprofen derivatives could be used as drug carriers in transdermal systems to provide better drug bioavailability, and they can be also be the source of exogenous L-valine.

Ionic liquids based on different l-amino acids (glycine, l-valine, l-leucine, l-isoleucine, l-histidine, l-methionine, l-tyrosine, l-tryptophan, l-arginine, and l-threonine) and different cations (tetrabutylammonium (TBA), tributylmethylammonium (tBMA), didecyldimethylammonium (DDA), (2-hydroxyethyl)trimethylammonium (choline) (Chol), alkyl(C₁₂-C₁₄) dimethylbenzylammonium (benzalkonium) (BA), dodecyltrimethylammonium (DDTMA), hexadecyltrimethylammonium (HDTMA), octadecyltrimethylammonium (ODTMA) and 1-ethyl-3-methylimidazolium (EMIM)) have been synthesized and characterized by NMR and FTIR. Viscosity, specific rotation, surface activity, thermal stability (TG), and phase transformations (DSC) have been determined and compared with available data. Furthermore, benzalkonium, didecyldimethylammonium, dodecyltrimethylammonium, hexadecyltrimethylammonium, and octadecyltrimethylammonium amino acid ionic liquids have been shown to exhibit surface activity. The dissolution of cellulose in amino acid ionic liquids (AAILs) composed of various cations was also investigated. Cellulose was only dissolved in EMIM salts of amino acids. In particular, the influence of the cation type on selected physicochemical and spectroscopic properties were discussed. The article is a mini review on amino acid ionic liquids.

The effect of various alcohols as vehicles on skin permeability was compared for unmodified ibuprofen (IBU) and ion pairs of ibuprofen with L-valine alkyl esters [ValOR][IBU], in which the alkyl chain R was changed from C1 to C8. In vitro permeation experiments were conducted in a Franz cell with porcine skin. Methanol, ethanol, and isopropanol solutions of 70% (v/v) were chosen as vehicles for penetrants and a buffer solution of pH 5.4 or 7.4 as the acceptor phase. The comparisons of permeation profiles for various [ValOR][IBU] from different alcohols were determined. The cumulative mass, skin accumulation, steady-state flux, diffusion coefficient, and lag time were investigated and compared. It was observed that i-propanol was the best enhancer of skin permeation of both unmodified ibuprofen and its salts with L-valine alkyl esters for both acceptor phases. The permeability of the various carriers increases with increasing chain-length of the alcohol. In most cases, significantly higher cumulative mass was found in the acceptor buffer of pH 7.4. The conjugate of ibuprofen with L-valine propyl ester [ValOPr][IBU] permeated the skin to the highest degree in comparison to unmodified ibuprofen. The accumulation of ibuprofen was higher for all salts in relation to the parent acid applied onto the skin. The greatest amounts of ibuprofen were accumulated in the skin when ibuprofen was used as the ionic pair with L-valine butyl ester, [ValOBu][IBU] in the i-propanol solution and pH 7.4 buffer as the acceptor phase.

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.