Improved transdermal permeability of ibuprofen by ionic liquid technology: Correlation between counterion structure and the physicochemical and biological properties

Wu, Hao; Deng, Zhaizhu; Zhou, Bijiang; Qi, Ming‐Hui; Hong, Minghuang; Ren, Guobin

doi:10.1016/j.molliq.2019.03.046

Cited by 62 publications

(46 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[IBU] were white solids at room temperature, which was opposite of the series of ibuprofen salts with counterions, such as phosphonium, imidazolium, ammonium, procaine, lidocaine, or ranitidine that were recently reported by Wu et al 27 which were liquids at ambient temperature. As shown in Table 1, the melting point of [ValOR][IBU], which was determined using the DSC method as a peak temperature, depended on the alkyl chain R in the ester group and it was between 67.4 and 79.8 C. The lowest melting point was for ibuprofen paired with L-valine hexyl ester and the highest melting point was for L-valine propyl ester.…”

Section: Salts Of Ibuprofen With L-valine Alkyl Esters [Valor]mentioning

confidence: 99%

“…Moreover, a straightchain n-propyl in the L-valine ester group resulted in better solubility than a branched-chain isopropyl ( Compared to the water solubility of the known ibuprofen organic salts, the solubility of L-valine ester ibuprofenates was higher than for tetrahexylammonium, trihexyltetradecylphosphonium, and didecyldimetylammonium ibuprofenates, while was close to lidocaine or procaine ibuprofenates but lower than for butylmetylimidazolium or tetrabutylphosphonium salts. 27…”

Section: Solubilitymentioning

confidence: 99%

“…There are some data about the ux for various ibuprofen salts in the literature, but permeation experimental conditions were different than those in this study. For example, Wu et al 27 26 measured the steady-state ux through a PDMS membrane with a buffer at pH 7.0 as the acceptor phase for the ibuprofen triethylammonium salt, which was over 15-fold higher than for sodium ibuprofenate. Furukawa et al reported that the rate of permeation of ibuprofen-ProOEt through pig skin was ten-times higher than for free ibuprofen and variation in skin permeation depends on strong ion-pairing between a cation and an anionic drug.…”

Section: Skin Penetrationmentioning

confidence: 99%

“…EC 50 values for conjugates with lipophilic cations were two-three orders of magnitude lower than for that with hydrophilic cations. 27 Counterions with longer alkyl chains and higher log P values may interact with cell membrane more extensively and cause more severe cytotoxicity.…”

Section: Skin Accumulationmentioning

confidence: 99%

“…All the synthesised ibuprofen ionic liquids showed improved skin permeability compared to the conventional sodium salt. 27 Furukawa et al 28 combined ibuprofen with proline ethyl ester as the base to form an ionic liquid, which showed signicant enhancement in the cumulative amount of drug in the permeation experiments using pig skin compared to the acid form. Rogers et al 29 revealed that ibuprofen with lidocaine form liquid co-crystals in a deep eutectic form, and both components can be simultaneously transported through the model membrane at much higher rates than the corresponding commercially available crystalline salts, i.e.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Enhancement of ibuprofen solubility and skin permeation by conjugation with l-valine alkyl esters

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Salts Of Ibuprofen With L-valine Alkyl Esters [Valor]mentioning

confidence: 99%

Section: Solubilitymentioning

confidence: 99%

Section: Skin Penetrationmentioning

confidence: 99%

Section: Skin Accumulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Enhancement of ibuprofen solubility and skin permeation by conjugation with l-valine alkyl esters

et al. 2020

View full text Add to dashboard Cite

show abstract

Comparison of Ionic Liquids and Chemical Permeation Enhancers for Transdermal Drug Delivery

Duffy

Curreri

et al. 2020

Adv Funct Materials

View full text Add to dashboard Cite

Transdermal delivery offers a patient-friendly method of drug administration. An ideal formulation for transdermal drug delivery should have high potency to enhance skin permeation and low tendency to induce skin irritation. Ionic liquids (ILs) and deep eutectic solvents (DESs) have recently been proposed to serve as an excellent platform to enable transdermal delivery of various therapeutics including proteins and siRNA. In spite of their success, general safety-efficacy behavior of ILs/DESs is not reported. Using safety and efficacy as two design criteria, a Fourier transform infrared (FTIR) spectroscopy study is conducted to compare the performance of 31 ammonium-based ILs/DESs and 44 conventional chemical permeation enhancer (CPE) molecules. FTIR analysis of skin stratum corneum exposed to ILs/DESs and CPEs is performed to extract features indicative of their safety and efficacy. ILs/DESs, as a class, outperformed conventional CPEs in terms of both potency and safety. Analysis of ILs/DESs and CPEs based on Hansen solubility parameters indicates that ILs/DESs possess solubility parameters close to those of skin, which may explain their superiority over CPEs. These studies support ILs/ DESs as promising materials for novel drug delivery systems.

show abstract

Recent Advances in Ionic Liquids in Biomedicine

2021

View full text Add to dashboard Cite

The use of ionic liquids and deep eutectic solvents in biomedical applications has grown dramatically in recent years due to their unique properties and their inherent tunability. This review will introduce ionic liquids and deep eutectics and discuss their biomedical applications, namely solubilization of drugs, creation of active pharmaceutical ingredients, delivery of pharmaceuticals through biological barriers, stabilization of proteins and other nucleic acids, antibacterial agents, and development of new biosensors. Current challenges and future outlooks are discussed, including biocompatibility, the potential impact of the presence of impurities, and the importance of understanding the microscopic interactions in ionic liquids in order to design task-specific solvents.

show abstract

Improved transdermal permeability of ibuprofen by ionic liquid technology: Correlation between counterion structure and the physicochemical and biological properties

Cited by 62 publications

References 45 publications

Enhancement of ibuprofen solubility and skin permeation by conjugation with l-valine alkyl esters

Enhancement of ibuprofen solubility and skin permeation by conjugation with l-valine alkyl esters

Comparison of Ionic Liquids and Chemical Permeation Enhancers for Transdermal Drug Delivery

Recent Advances in Ionic Liquids in Biomedicine

Contact Info

Product

Resources

About