Ionic Liquids: New Forms of Active Pharmaceutical Ingredients with Unique, Tunable Properties

Abstract

This Review aims to summarize advances over the last 15 years in the development of active pharmaceutical ingredient ionic liquids (API-ILs), which make up a prospective game-changing strategy to overcome multiple problems with conventional solid-state drugs, for example, polymorphism. A critical part of the present Review is the collection of API-ILs and deep eutectic solvents (DESs) prepared to date. The Review covers rules for rational design of API-ILs and tools for API-IL formation, syntheses, and characterization. Nomenclature and ionic speciation, and the confusion that these may cause, are highlighted, particularly for speciation in both ILs and DESs of intermediate ionicity. We also highlight in vivo and in vitro pharmaceutical activity studies, with differences in pharmacokinetic/pharmacodynamic depending on ionicity of API-ILs. A brief overview is provided for the ILs used to deliver drugs, and the Review concludes with key prospects and roadblocks in translating API-ILs into pharmaceutical manufacturing.

Development of Cholinium-Based API Ionic Liquids with Enhanced Drug Solubility: Biological Evaluation and Interfacial Properties

“…The liquid form of an active drug (at room temperature) can evade few issues of polymorphism that are related to the crystalline solids and, therefore, dramatically affect the solubility and dosage of the drug. 4,27,28 Additionally, some of the works that have been reported have taken a further step to develop ILs themselves as APIs. The first effort was taken by Rogers and co-workers who specifically prepared API-ILs.…”

“…A developing research field for ILs that is of great interest is to use them in pharmaceutical applications. Recently, ILs are combined with APIs and has emerged as the so-called third generation of ILs or API-ILs. ,, On comparing the solid pharmaceutical forms with their corresponding API-ILs, API-ILs offer improved properties, like solubility, stability, permeability, and drug delivery. The liquid form of an active drug (at room temperature) can evade few issues of polymorphism that are related to the crystalline solids and, therefore, dramatically affect the solubility and dosage of the drug. ,, Additionally, some of the works that have been reported have taken a further step to develop ILs themselves as APIs.…”

Facile Separation of Acetic Acid from 1-Ethyl-3-methylimidazolium Acetate Ionic Liquid with the Aid of a Protic Solvent

“…They are promising solvents whose properties can be adjusted by changing the molecular structure of their cations, anions, and their combinations. , Many researchers have tried and succeeded in tuning their high thermal stability, low flammability, wide electrochemical potential window, solubility, and solubility of biomass resources . Research on ILs has rapidly increased in recent years, and their applications have expanded to various fields such as energy storage, active pharmaceutical extractants and ingredients, and lubricant additives . Furthermore, research has focused on biomass conversion to polymeric materials, especially on the chemical modification of lignocellulose in ILs, ever since Rogers and co-workers discovered that cellulose can be dissolved in 1-butyl-3-methylimidazolium chloride at high concentrations .…”

Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms

“…Most surprisingly, whereas the other branches have been demonstrating evident growth (Energetics and Toxicity) or have reached a plateau (Green chemistry, Fine-tuned biological activity, and Medicine) during the last two decades, research on mechanistic aspects of IL-induced toxicity (Mechanisms of toxicity) seems stagnant in comparison. The topic of the biological activity of ILs, in particular, their toxicity toward various biological systems and organisms, has been addressed in details in numerous reviews, including recent reviews. ,,− Possible applications of ILs in medicine comprise a separate scientific branch, which has its share of reviews. ,− However, to the best of our knowledge, almost no attempts to systematize and generalize the available data from the viewpoint of mechanisms of IL-related toxicity have been made thus far. We think the time has come to present such a review to the IL-dedicated scientific society.…”

“…Task-specific, drug-oriented ILs and API-ILs are beyond the scope of the review, since currently there are not enough data to understand their mechanism of action in biological systems. Moreover, they often contain an API moiety (non-IL component), providing them with a specific mechanism of action …”