Recovery of Nonsteroidal Anti-Inflammatory Drugs from Wastes Using Ionic-Liquid-Based Three-Phase Partitioning Systems

Abstract

Aiming at outlining new strategies for the valorization of solid pharmaceutical wastes as viable alternatives to incineration, this work proposes the use of ionic liquids-based three phase partitioning (IL-based TPP) systems. Ibuprofen, naproxen, and ketoprofen, all belonging to the class of nonsteroidal anti-inflammatory drugs (NSAIDs), were adopted as model compounds. An integrated process has been conceptualized based on three steps: (1) extraction and purification of NSAIDs using the IL-based TPP systems, (2) drug isolation by precipitation with antisolvents, and (3) recycling and reusing the solvents. With the optimization of steps 1 and 2 as objects of this investigation, aqueous biphasic systems (ABS) composed of three distinct ILs (tetrabutylammonium chloride, 1-butyl-3-methylimidazolium chloride, and benzyldimethyl(2-hydroxyethyl)ammonium chloride) and potassium citrate buffer were studied. The corresponding IL-based TPP systems were further applied in the purification of each NSAID, and different antisolvents (citric acid aqueous solutions for ibuprofen and naproxen and aluminum sulfate aqueous solutions for ketoprofen) were evaluated as precipitating agents to isolate each drug. The success of the process developed is demonstrated by extraction efficiencies higher than 83.8 ± 7.7% attained in step 1 and isolation efficiencies higher than 76.2 ± 1.8% in step 2. The stability of the three NSAIDs in IL-based aqueous matrices was additionally checked by using a protocol adapted from the OECD guidelines. The economic efficiency and environmental benignity of the process herein developed is underlined, based on not only the low cost of the solvents chosen but also the possibility of recycling and reusing the phase-forming components and antisolvents employed.

Selective and mild fractionation of microalgal proteins and pigments using aqueous two‐phase systems

“…Ionic liquid‐based three phase partitioning (ILTPP) has been investigated because it combines the advantages of the IL‐ATPS and TPP for the concentration and recovery of different molecules including proteins . ILTPP is capable of inducing the formation of a dense and stable protein layer in the middle with IL‐ATPS phase‐forming components.…”

“…Ionic liquid-based three phase partitioning (ILTPP) has been investigated because it combines the advantages of the IL-ATPS and TPP for the concentration and recovery of different molecules including proteins. [48][49][50] ILTPP is capable of inducing the formation of a dense and stable protein layer in the middle with IL-ATPS phase-forming components. Alvarez-Guerra and Irabien 51 suggested that the salt concentration has the greatest influence on the amount of lactoferrin recovered at the interface.…”

How imidazolium‐based ionic liquids solubilize the poorly soluble ibuprofen? A theoretical study

“…In order to solve the problem, some scientists have suggested that it is of great value to replace the widely used toxic organic solvents by safely, biodegradable, and environmentally friendly neoteric solvents for the development of sustainable pharmaceutical processes . Ionic liquids (ILs) as neoteric solvents, with the advanced characteristics of non‐volatility, non‐flammability, and high recyclability, have been proposed as green solvents for the extraction, separation, crystallization, and purification of drugs . Particularly, existing experimental data showed that most of imidazolium‐based ILs were considered to be a biodegradable IL and to exhibit quite a low toxicity on human body, which made them even as the component of the active pharmaceutical ingredients (APIs) .…”

“…These studied ILs include 1‐ethyl‐3‐methylimidazolium ([Emim] + ), 1‐butyl‐3‐methylimidazolium ([Bmim] + ), and 1‐hexyl‐3‐methylimidazolium ([Hmim] + ) cations paired with tetrafluoroborate ([BF 4 ] − ), hexafluorophosphate ([PF 6 ] − ), trifluoromethanesulfonate ([TfO] − ), and acetate ([AcO] − ) anions. They are known to be highly effective in dissolving nonsteroidal anti‐inflammatory drugs, for example, ibuprofen, which are environmentally friendly and widely available commercially . Herein, we first explore the nature of the first solvation structural shell of ibuprofen and find that its structure is mainly determined by the interactions of anions or cations with ibuprofen.…”

“…3,4,9,10 Ionic liquids (ILs) as neoteric solvents, with the advanced characteristics of non-volatility, non-flammability, and high recyclability, have been proposed as green solvents for the extraction, separation, crystallization, and purification of drugs. [11][12][13][14][15][16][17][18] Particularly, existing experimental data showed that most of imidazolium-based ILs were considered to be a biodegradable IL and to exhibit quite a low toxicity on human body, which made them even as the component of the active pharmaceutical ingredients (APIs). 19,20 Meanwhile, the number of possible ILs has reached 10 18 due to their outstanding tunable nature, which makes it possible to develop tailormade specific solvents for drugs in pharmaceutical applications.…”