Enhancement of water solubility of poorly water-soluble drugs by new biocompatible N-acetyl amino acid N-alkyl cholinium-based ionic liquids

Jesus, Ana Rita; Soromenho, Mário R. C.; Raposo, Luís R.; Esperança, José M. S. S.; Baptista, Pedro V.; Fernandes, Alexandra R.; Reis, Patrícia M.

doi:10.1016/j.ejpb.2019.03.004

Cited by 72 publications

(29 citation statements)

References 47 publications

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“…General procedure for the determination of the solubility limit of Paracetamol and Sodium Diclofenac in IL/water solutions. The solubility limit for paracetamol and sodium diclofenac were determined as described previously [12]. Briefly, aqueous solutions (5 mL) of ionic liquids (1 mol% or 0.2 mol%) were prepared, and paracetamol or sodium diclofenac (325 mg or 500 mg) was added to each sample (at this concentration we are above the solubility limit for all the samples).…”

Section: Methodsmentioning

confidence: 99%

“…In the reported literature, to the best of our knowledge, there are almost no data available for the solubility enhancement of sodium diclofenac mediated by ionic liquids. Formerly, our group showed that N-acetyl amino acid N-alkyl cholinium-based ILs were able to significantly increase the water solubility of two poorly water-soluble drugs, paracetamol and sodium diclofenac [12].…”

Section: Introductionmentioning

confidence: 99%

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New Non-Toxic N-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs

et al. 2021

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In this work, we prepared new biocompatible N-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclofenac and paracetamol. In this set of ionic liquids, we intend to understand the effect of increasing the asymmetry of the ionic liquid cation/anion by growing the length of one of the alkyl chains attached to the nitrogen center/sulfonate center on the dissolution capacity of the ionic liquid. The addition of these new ionic liquids to water increased the dissolution capacity of the drugs up to four-times that in water, and improved the pharmacodynamic properties of these drugs, especially the case of sodium diclofenac. The intermolecular interactions between the drugs and ionic liquids were investigated by NMR. Two-dimensional 1H/1H nuclear overhauser effect spectroscopy (NOESY) revealed an interaction between sodium diclofenac and the alaninate anion from the [C2Ch]2[SucAla]. In the case of paracetamol and [C4Ch][C2SO3], it was possible to observe two intermolecular interactions between the hydroxyl group of paracetamol and two protons from the cation [C4Ch]+. Interestingly, the ionic liquid bearing a succinyl-DL-alaninate anion, [SucAla]2−, and a N-ethyl cholinium cation, [C2Ch]+, which presented the highest ability to dissolve sodium diclofenac, showed no cytotoxicity up to 500 mM. Therefore, this ionic liquid is a potential candidate for drug delivery applications.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New Non-Toxic N-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs

et al. 2021

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“…The capacity of delivering macromolecules through the skin is an important achievement for TDD because it has been one of the most difficult obstacles to overcome. Jesus et al (2019) also synthesized amino acid-based ILs, combining anionic N -acetyl amino acid derivatives with cationic N -alkyl choline derivatives [ 119 ]. The goal was to use these biocompatible ILs as co-solvents to enhance the solubility of highly hydrophobic drugs in aqueous environments.…”

Section: Amino Acid-based Enhancersmentioning

confidence: 99%

Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery

et al. 2021

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Transdermal drug delivery (TDD) presents many advantages compared to other conventional routes of drug administration, yet its full potential has not been achieved. The administration of drugs through the skin is hampered by the natural barrier properties of the skin, which results in poor permeation of most drugs. Several methods have been developed to overcome this limitation. One of the approaches to increase drug permeation and thus to enable TDD for a wider range of drugs consists in the use of chemical permeation enhancers (CPEs), compounds that interact with skin to ultimately increase drug flux. Amino acid derivatives show great potential as permeation enhancers, as they exhibit high biodegradability and low toxicity. Here we present an overview of amino acid derivatives investigated so far as CPEs for the delivery of hydrophilic and lipophilic drugs across the skin, focusing on the structural features which promote their enhancement capacity.

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“…Furthermore, imidazolium or pyridinium ions can be used as organic cations of RTILs, combined with a variety of anions such as hexafluorophosphate or tetrafluoroborate ( Figure 1) [18]. In addition, RTILs appear as promising candidates for enhancing the aqueous solubility of hydrophobic drugs via the selection of the adequate cation/anion combinations [20]. RTILs are hydrotropic compounds, which are capable of substantially increasing the solubility of hydrophobic substances in water.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Evaluation of Self-Nano-Emulsifying Drug Delivery Systems (SNEDDS) Containing Room Temperature Ionic Liquids (RTILs) for the Oral Delivery of Amphotericin B

et al. 2020

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Amphotericin B (AmpB), one of the most commonly used agents in the treatment of severe fungal infections and life-threatening parasitic diseases such as visceral Leishmaniasis, has a negligible oral bioavailability, primarily due to a low solubility and permeability. To develop an oral formulation, medium chain triglycerides and nonionic surfactants in a self-nano-emulsifying drug delivery system (SNEDDS) containing AmpB were combined with room temperature ionic liquids (RTILs) of imidazolium. The presence of ionic liquids significantly enhanced the solubility of AmpB, exhibited a low toxicity and increased the transport of AmpB across Caco-2 cell monolayers. The combination of RTILs with a lipid formulation might be a promising strategy to improve the oral bioavailability of AmpB.

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Enhancement of water solubility of poorly water-soluble drugs by new biocompatible N-acetyl amino acid N-alkyl cholinium-based ionic liquids

Cited by 72 publications

References 47 publications

New Non-Toxic N-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs

New Non-Toxic N-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs

Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery

In Vitro Evaluation of Self-Nano-Emulsifying Drug Delivery Systems (SNEDDS) Containing Room Temperature Ionic Liquids (RTILs) for the Oral Delivery of Amphotericin B

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