Ionic Liquid Aqueous Two-Phase Systems From a Pharmaceutical Perspective

Abstract

Aqueous Two-Phase Systems (ATPSs) have been extensively studied for their ability to simultaneously separate and purify active pharmaceutical ingredients (APIs) and key intermediates with high yields and high purity. Depending on the ATPS composition, it can be adapted for the separation and purification of cells, nucleic acids, proteins, antibodies, and small molecules. This method has been shown to be scalable, allowing it to be used in the milliliter scale for early drug development to thousands of liters in manufacture for commercial supply. The benefits of ATPS in pharmaceutical separations is increasingly being recognized and investigated by larger pharmaceutical companies. ATPSs use identical instrumentation and similar methodology, therefore a change from traditional methods has a theoretical low barrier of adoption. The cost of typical components used to form an ATPS at large scale, particularly that of polymer-polymer systems, is the primary challenge to widespread use across industry. However, there are a few polymer-salt examples where the increase in yield at commercial scale justifies the cost of using ATPSs for macromolecule purification. More recently, Ionic Liquids (ILs) have been used for ATPS separations that is more sustainable as a solvent, and more economical than polymers often used in ATPSs for small molecule applications. Such IL-ATPSs still retain much of the attractive characteristics such as customizable chemical and physical properties, stability, safety, and most importantly, can provide higher yield separations of organic compounds, and efficient solvent recycling to lower financial and environmental costs of large scale manufacturing.

Fungi as a Potential Source of Pigments: Harnessing Filamentous Fungi

“…Separation of different hydrophilic solutes into two immiscible aqueous phases is mainly based upon their differential selectivity toward different polymer-polymer, polymer-salt, or salt-salt and solute combinations formed in these two phases. Aqueous twophase systems offers several advantages for downstream control of biomolecules (1) both the phases are composed of water compared to organic solvents in conventional extraction thus provides favorable environment to molecules and supports the stability of their structure and bioactivity, (2) an environmental friendly process, (3) are economically favorable (McQueen and Lai, 2019).…”

Aqueous Two-Phase System Extraction of Polyketide-Based Fungal Pigments Using Ammonium- or Imidazolium-Based Ionic Liquids for Detection Purpose: A Case Study

“…Fungal fermentation broths are complex biological matrices containing various complex compounds, from proteins to lipids and other excretable secondary metabolites, including fungal pigments. Such diversity represents a burden for the development of fast, efficient and cost-effective detection and extraction processes, for which IL-ATPSs are expected to offer realistic options [ 19 , 21 ]. A brief description of the overall extraction process is shown in Figure 1 .…”

“…Thus, a rigorous selection of ILs and salt families and structures must be carried out beforehand based on the type of target biomolecules to be extracted, in order to make the most sustainable choice [ 14 , 16 , 17 , 18 ]. Imidazolium-based ILs such as [C4Mim]Br − and [C4Mim]Cl − are the most frequently used IL cores and are, therefore, well documented [ 19 , 20 ], hence we chose to study these in association with harmless salts. They were proven to have higher hydrophilicity than tetra-alkyl ammonium-based ILs ([N4444]Br − ) because of their aromatic characteristics allowing a stronger interaction with water due to the delocalization of the positive charge over the aromatic ring [ 21 ].…”

Evaluation of Aqueous Biphasic Electrophoresis System Based on Halide-Free Ionic Liquids for Direct Recovery of Keratinase

“…The IL containing halide anions such as chloride, bromide, iodide, tetrafluoroborate and hexafluoroborate has been commonly used to form biphasic system for biomolecules extraction [ 6 ]. However, the halide-containing IL demonstrates poor biodegradability and hazardous effects to the environment due to the release of toxic and corrosive by-products upon decomposition [ 7 , 8 ].…”