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

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Review

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

Sónia N Pedro et al. Int J Mol Sci. 2020.

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.

Keywords: active pharmaceutical ingredients; drug delivery systems; formulations; ionic liquids; permeability; solubility.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1

Number of publications per year in a twenty years perspective related to ILs and active pharmaceutical ingredients (APIs) (number of articles, reviews and book chapters according to a ScienceDirect database search using as keywords “ionic liquids”, “active pharmaceutical ingredients”, and “drug delivery”) (left). Overview of the ILs’ applications in the pharmaceutical field reported hitherto (right).

Figure 2
Figure 2

Multiple roles of ILs in the synthesis of different APIs and their respective efficiency (adequate references are given along the current section).

Figure 3
Figure 3

Fast and acid-free one-pot IL-based microwave methodology for direct synthesis of lactams from lactones and primary amines proposed in [41].

Figure 4
Figure 4

Pravadoline synthesis in an IL media proposed in [51].

Figure 5
Figure 5

Synthesis of nucleoside-based antiviral drugs in IL media proposed in [56].

Figure 6
Figure 6

IL application as solvent and iodinating agent in the synthesis of clioquinol proposed in [57].

Figure 7
Figure 7

Schematic representation of naproxen’s electrosynthesis under CO2 atmosphere proposed in [60].

Figure 8
Figure 8

Applications of ILs in APIs’ crystallization processes (adequate references are given along the current section).

Figure 9
Figure 9

Biological activities reported for ILs and the respective studied cations (adequate references are given along the current section).

Figure 10
Figure 10

Schematic examples of API-ILs pharmaceutical formulations (adequate references are given along the current section).

Figure 11
Figure 11

Selected examples of cations and anions used in API-ILs preparation (adequate references are given along the current section).

Figure 12
Figure 12

Example of solubility enhancements provided by API-ILs in aqueous media in comparison with the parent APIs and their dissolution in water (mg mL−1) (adequate references are given along the current section).

Figure 13
Figure 13

Schematic representation of the formation of oligomeric ions based on salicylate/salicylic acid proposed in [153].

Figure 14
Figure 14

Synthesis of cationic acetaminophen prodrug ILs paired with the docusate anion proposed in [158].

Figure 15
Figure 15

Schematic representation on the use of ILs in drug delivery systems (adequate references are given along the current section).

Figure 16
Figure 16

Schematic illustration of the preparation of IL-polydopamine (PDA) nanoparticles loaded with doxorrubucin for combined chemotherapy and microwave thermal therapy proposed in [181].

Figure 17
Figure 17

Illustration of the API-IL self-assembling into vesicles in aqueous media proposed in [191].

Figure 18
Figure 18

IL applications in the development of drug delivery systems for topical and transdermal administration (adequate references are given along the current section).

Figure 19
Figure 19

IL-in-oil microemulsions based on [C1C1im][(MeO)2PO2] as drug carriers of acyclovir proposed in [198].

Figure 20
Figure 20

Illustration of BC-IL membranes’ with antioxidant and anti-inflammatory action for dermal application proposed in [202].

Figure 21
Figure 21

Schematic representation of IL effect and insertion into the lipid bilayer proposed in [214].

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