The Role of Ionic Liquids in the Pharmaceutical Field: An Overview of Relevant Applications

Pedro, Sónia N.; Freire, Carmen S. R.; Silvestre, Armando J. D.; Freire, Mara G.

doi:10.3390/ijms21218298

Cited by 133 publications

(108 citation statements)

References 211 publications

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“…Ionic liquids (ILs) have emerged as valuable tools to solve a wide range of challenges in the pharmaceutical field. Consequently, the number of studies that have considered their applicability in this area has increased considerably [ 1 , 2 , 3 ]. ILs are usually defined as organic salts, which are liquid at temperatures below 100 °C, or in some cases liquid at room temperature (RTILs) [ 4 , 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool

Caparica

Júlio

Fernandes

et al. 2021

IJMS

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Numerous studies are continuously being carried out in pursuit of formulations with higher performance. Problems such as poor drug solubility, which hinders drug incorporation into delivery systems and bioavailability, or limitations concerning the stability and performance of the formulations may cause difficulties, since solving all these drawbacks at once is a huge challenge. Ionic liquids (ILs), due to their tunable nature, may hypothetically be synthesized for a particular application. Therefore, predicting the impact of a particular combination of ions within an IL in drug delivery could be a useful strategy. Eight ILs, two choline amino acid ILs, two imidazole halogenated ILs, and four imidazole amino acid ILs, were prepared. Their applicability at non-toxic concentrations, for improving solubility and the incorporation of the poorly soluble, ferulic, caffeic, and p-coumaric acids, as well as rutin, into topical emulsions, was assessed. Next, the impact of the ILs on the performance of the formulations was investigated. Our study showed that choosing the appropriate IL leads to a clear upgrade of a topical emulsion, by optimizing multiple features of its performance, such as improving the delivery of poorly soluble drugs, altering the viscosity, which may lead to better sensorial features, and increasing the stability over time.

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Section: Introductionmentioning

confidence: 99%

Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool

Caparica

Júlio

Fernandes

et al. 2021

IJMS

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“…Given the huge number of possible cation/anion combinations, reports to date cover an immense panoply of different ILs that can be classified in many different ways, depending on the classification criteria ( Figure 9 ), as thoroughly reviewed elsewhere [ 123 ]. In general, three generations of ILs have been recognized, going from the earlier examples of ILs proposed as “greener” surrogates of classical organic solvents to the next generation of ILs whose chemical and physical properties were adjustable to their specific applications (task-specific ILs, or TSILs), and finally to ILs displaying low toxicity, biocompatibility, biodegradability and, in some cases, even bioactivity [ 120 , 121 , 123 , 124 , 125 ].…”

Section: Ionic Liquid-based Approaches In Dermal and Transdermal Drug Deliverymentioning

confidence: 99%

The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years

Gomes

Aguiar

Ferraz

et al. 2021

IJMS

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Topical and transdermal delivery systems are of undeniable significance and ubiquity in healthcare, to facilitate the delivery of active pharmaceutical ingredients, respectively, onto or across the skin to enter systemic circulation. From ancient ointments and potions to modern micro/nanotechnological devices, a variety of approaches has been explored over the ages to improve the skin permeation of diverse medicines and cosmetics. Amongst the latest investigational dermal permeation enhancers, ionic liquids have been gaining momentum, and recent years have been prolific in this regard. As such, this review offers an outline of current methods for enhancing percutaneous permeation, highlighting selected reports where ionic liquid-based approaches have been investigated for this purpose. Future perspectives on use of ionic liquids for topical delivery of bioactive peptides are also presented.

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“…To improve ILs' sustainabilityrelated issues, synthetic procedures for their preparation have been optimized, focusing on the replacement or elimination of polluting organic solvents and on the usage of reagents deriving from renewable sources [15]. In parallel to this approach, toxicity and biodegradation assessments pointed to structural elements of the cationic and anionic parts capable of ameliorating the overall impact profile of ILs [16,17] This new type of ILs, often referred to as the fourth generation of ILs, allowed for expanding the portfolio of possible applications in the fields of food science [18,19], medicine [20,21] and pharmaceutics [22,23].…”

Section: Introductionmentioning

confidence: 99%

Expanding the Chemical Space of Benzimidazole Dicationic Ionic Liquids

et al. 2021

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Benzimidazole dicationic ionic liquids (BDILs) have not yet been widely explored in spite of their potential. Therefore, two structurally related families of BDILs, paired with either bromide or bistriflimide anions and bearing alkyl spacers ranging from C3 to C6, have been prepared. Their thermal properties have been studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), while their electrical properties have been assessed by cyclic voltammetry (CV). TG analysis confirmed the higher stability of the bistriflimide BDILs over the bromide BDILs, with minor variation within the two families. Conversely, DSC and CV allowed for ascertaining the role played by the spacer length. In particular, the thermal behavior changed dramatically among the members of the bistriflimide family, and all three possible thermal behavior types of ILs were observed. Furthermore, cyclic voltammetry showed different electrochemical window (C3(C1BenzIm)2/2Tf2N < C4(C1BenzIm)2/2Tf2N, C5(C1BenzIm)2/2Tf2N < C6(C1BenzIm)2/2Tf2N) as well as a reduction peak potential, shape, and intensity as a function of the spacer length. The results obtained highlight the benefit of accessing a more structurally diverse pool of compounds offered by dicationic ILs when compared to the parent monocationic ILs. In particular, gains are to be found in the ease of fine-tuning their properties, which translates in facilitating further investigations toward BDILs as designer solvents and catalysts.

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The Role of Ionic Liquids in the Pharmaceutical Field: An Overview of Relevant Applications

Cited by 133 publications

References 211 publications

Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool

Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool

The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years

Expanding the Chemical Space of Benzimidazole Dicationic Ionic Liquids

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