Abstract
Solubility, bioavailability, permeation, polymorphism, and stability concerns associated to solid-state pharmaceuticals demand for effective solutions. To overcome some of these drawbacks, ionic liquids (ILs) have been investigated as solvents, reagents, and anti-solvents in the synthesis and crystallization of active pharmaceutical ingredients (APIs), as solvents, co-solvents and emulsifiers in drug formulations, as pharmaceuticals (API-ILs) aiming liquid therapeutics, and in the development and/or improvement of drug-delivery-based systems. The present review focuses on the use of ILs in the pharmaceutical field, covering their multiple applications from pharmaceutical synthesis to drug delivery. The most relevant research conducted up to date is presented and discussed, together with a critical analysis of the most significant IL-based strategies in order to improve the performance of therapeutics and drug delivery systems.
Highlights
Pharmaceuticals play a major role in medical care, boosting life quality and expectancy, especially when considering chronic diseases [1]
Promising results have been reported in terms of active pharmaceutical ingredients (APIs) solubility, comparisons between the results obtained in ionic liquids (ILs) media with the ones that were obtained with other common solvents, such as water or ethanol, are shortly explored along with the bioavailability profiles
To overcome some of these drawbacks, ILs have been investigated as solvents, reagents, or catalysts in the synthesis of APIs and applied in the crystallization process of drugs
Summary
Pharmaceuticals play a major role in medical care, boosting life quality and expectancy, especially when considering chronic diseases [1]. Promising results have been reported in terms of APIs solubility, comparisons between the results obtained in IL media with the ones that were obtained with other common solvents, such as water or ethanol, are shortly explored along with the bioavailability profiles These assays should be considered in order to support the advantageous use of IL-based solvents alternatives. In order to evaluate the influence of the IL anion on ibuprofen’s solubility, [C4C1im]- and sodium-based hydrotropes were investigated, where a higher hydrotropic activity was disclosed with 1-butyl-3-methylimidazolium thiocyanate ([C4C1im][SCN]) and 1-butyl-3-methylimidazolium dicyanamide ([C4C1im][N(CN)2]) These ILs increase the aqueous solubility of ibuprofen by 60- and 120-fold, respectively, in comparison to the API in pure water. More biocompatible combinations are expected to be studied and more complete studies are still required to boost IL research and enable their use in pharmaceutical formulations
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