Electrochemical-Based Technologies for Removing NSAIDs from Wastewater: Systematic Review with Bibliometric Analysis

Abstract

Electrochemical-based processes have shown great promise in removing organic pollutants such as non-steroidal anti-inflammatory drugs (NSAIDs) from wastewater due to their effectiveness in addressing environmental pollution. This study conducts a bibliometric analysis of the most-cited articles in the field to systematically evaluate the progress and current state of electrochemical methods for NSAID removal from wastewater. Additionally, it highlights the potential of combining electrochemical techniques with other treatment methods to enhance the overall efficiency of NSAID removal. Research in this field has mainly focused on three technologies: electro-peroxone process (E-peroxone), electro-Fenton (EF), and electrochemical oxidation (EO). Early studies prioritized EO-based treatments, but interest has gradually shifted toward EF and E-peroxone. Future research is expected to focus on the development of cost-effective electrode materials, improving energy efficiency, and exploring hybrid systems for more effective treatment of wastewater contaminated with NSAIDs. An integrated bibliometric and systematic review framework presented in this study provides the first comprehensive assessment of electrochemical strategies for NSAIDs removal, highlighting the evolution of research focus and the potential of hybrid approaches.

1. Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs used to reduce body temperature (antipyretics), relieve pain (analgesics), and reduce inflammation (anti-inflammatory). NSAIDs’ wide range of applications can be attributed to their broad spectrum of uses, including the treatment of muscle pain, dysmenorrhea, arthritic conditions, pyrexia, gout, and migraines, as well as their role as opioid-sparing agents in specific cases of acute trauma. Their use plays a crucial role in ensuring the health and well-being of both humans and animals, with the global NSAID market valued at USD 15.58 billion in 2019 and projected to reach USD 24.35 billion by 2027 [1]. As a result of their accessibility and affordability, NSAIDs are among the most widely used medications, leading to their significant presence in water bodies and ecosystems. NSAIDs primarily enter water systems through wastewater treatment plants (WWTPs), which often fail to completely remove pharmaceutical pollutants. Consequently, NSAID residues persist in treated water that is discharged into rivers, lakes, and oceans. Moreover, these drugs are not always fully metabolized in the body, causing a portion of the NSAID compound or its conjugated derivatives to be excreted through bodily waste into sewage treatment facilities [2]. Additional sources include the disposal of unused or expired medications from human (households, industry, hospitals) and veterinary (livestock and pets) use, further contributing to environmental contamination [2]. Nowadays, NSAIDs enter the water cycle in large quantities and persist for extended periods due to their structural and physicochemical properties.

Ibuprofen, naproxen, acetaminophen, and diclofenac are among the emerging contaminants frequently detected in aquatic environments. These pharmaceuticals have also been added to the monitoring priority list of the European Union [3,4]. They have been detected in concentrations ranging from ng L⁻¹ to µg L⁻¹ across various water sources, including groundwater, seawater, and wastewater [5]. Even at low concentrations, they can impact non-target organisms. Diclofenac and naproxen, for example, have been linked to kidney and liver damage in fish, with histopathological analysis revealing hyaline droplet degeneration in the tubular cells of the kidneys and interstitial nephritis. The gills exhibited necrosis of pillar cells, resulting in damage to the capillary walls within the secondary lamellae [6,7]. Ibuprofen has been reported to cause nephrotoxicity and lead to immunosuppressive responses in species such as Rhamdia quelen [8]. Acetaminophen has also been reported to negatively affect embryonic and larval development through teratogenic, neurotoxic, and cardiotoxic effects [9]. The chronic exposure of aquatic organisms to such compounds, even at trace levels, raises serious concerns about long-term ecological effects and supports the need for improved removal techniques.

The presence of NSAIDs in the urban water cycle can negatively impact both human health and the environment. Although NSAIDs in aquatic environments can degrade through natural processes such as photolysis, hydrolysis, and microbial activity, many persist and accumulate over time, raising concerns about their toxic impact on aquatic organisms. Studies have shown that NSAID exposure triggers oxidative stress, disrupts immune function, and is associated with growth retardation and developmental abnormalities in aquatic species. Exposure to NSAIDs in various aquatic species, including fish, mollusks, and crustaceans, significantly increases reactive oxygen species (ROS) production, resulting in oxidative stress and cellular damage. This elevated ROS generation contributes to lipid peroxidation, which compromises cell membrane integrity, as well as protein oxidation that disrupts essential enzymatic functions and DNA damage that may lead to genetic mutations or impaired cellular processes [10,11,12,13,14,15,16,17,18,19]. A primary mechanism of NSAID action is the inhibition of cyclooxygenase (COX) enzymes, which play a crucial role in producing prostaglandins. These lipid molecules are essential for regulating inflammation and immune function. Decreased prostaglandin production due to NSAID exposure has been linked to immunosuppression, making these organisms more vulnerable to infections. Additionally, NSAID exposure affects the adaptive immune system, particularly antibody production, leading to disruptions in immune memory formation and a weakened ability to resist pathogens [20,21,22]. NSAIDs can interfere with hormone signaling pathways, particularly those involving prostaglandins, which not only control inflammation but also contribute to reproductive and developmental processes. They play a crucial role in regulating reproductive functions such as ovulation, sperm motility, and fertilization and prolonged exposure to NSAIDs has been associated with growth retardation and developmental abnormalities, particularly in aquatic species like fish and amphibians [20,23,24,25].

The exposure of aquatic organisms to NSAIDs is evident in their bioaccumulation and transfer through the food chain. As NSAIDs build up in primary consumers such as zooplankton and bivalves, oxidative stress can propagate to higher trophic levels, impacting fish, birds, and other predators, ultimately intensifying ecological disruptions. From a broader perspective, the negative effects of NSAIDs on growth and reproduction can disrupt entire ecosystems by reducing reproductive success and causing developmental impairments. This can lead to population declines, particularly among species vital to maintaining aquatic ecosystem balance, ultimately posing a direct threat to biodiversity.

Considering the increasing presence of NSAIDs in wastewater and their negative impact on the environment and human health, the researcher has been actively investigating various technologies for their removal. Several strategies have been developed and applied for the elimination of NSAIDs from wastewater, including chemical, physical, and biological treatment [26].

Chemical methods for NSAID removal include Ionic-Liquid-Based Systems [27], Fenton processes [28,29,30], and ozonation [31,32]. While these techniques can be effective, they are often associated with high reagent consumption and the formation of potentially toxic by-products. Physicochemical methods, such as advanced oxidation processes (AOPs) [33], membrane technologies [34,35], and adsorption [36,37,38], have shown high removal efficiency for organic pollutants. However, their practical implementation can be limited by operational costs and maintenance requirements. Adsorption, in particular, is a widely used technique due to its simplicity, affordability, and flexibility. Various materials—such as activated carbon, graphene-based substances, biochar, and modified natural clays—have proven effective in capturing NSAIDs and other pharmaceutical contaminants [39,40,41,42]. However, the key disadvantage of adsorption relates to the regeneration and disposal of used adsorbents. Regeneration processes can be costly and technically demanding, while unsafe disposal may lead to environmental concerns. Additionally, the adsorption capacity of certain materials may be inadequate under variable wastewater conditions, which can compromise removal efficiency. There’s also the potential for desorption, where captured pollutants are released back into the water, causing secondary contamination. In contrast, electrochemical treatments allow for complete degradation and mineralization of pollutants, significantly reducing the risk of secondary pollution. These methods often reach near-complete removal of NSAIDs without the need for added chemicals. Furthermore, their adaptability makes them suitable for diverse wastewater treatment scenarios [43,44]. Biological processes, including activated sludge [45] and biofiltration [46,47,48], offer environmentally friendly solutions but may have limited effectiveness in degrading pharmaceutical compounds.

Previous reviews have primarily focused on specific NSAID removal techniques, such as AOPs, adsorption processes, and biodegradation approaches [49,50,51]. Although these studies provide valuable insights, a comprehensive review specifically addressing electrochemical technologies for NSAID removal remains scarce. With the rapid development of wastewater treatment methods over the past decade, recent advancements need to be evaluated, and the role of electrochemical techniques in dealing with this challenge needs to be examined.

Among the available approaches, electrochemical-based technologies are prominent and promising solutions for treating wastewater contaminated with NSAIDs. These technologies encompass processes such as electro-Fenton (EF) oxidation, electrocoagulation, electrochemical oxidation, and combined-hybrid electrochemical methods. Their key advantages include high removal efficiency even in the presence of complex organic matter, operation under ambient temperature and pressure, and reduced need for chemical reagents compared to conventional methods.

In recent decades, electrochemical methods have attracted significant attention from researchers, leading to an increasing number of scientific publications and research projects in this field. To systematically assess the development and current status of electrochemical methods for NSAID removal from wastewater, this study employs bibliometric analysis of the most-cited articles in this domain. The aim of this work is to provide a comprehensive review of existing research, identify key trends and challenges in the field, and highlight potential directions for future studies.

2. Search Strategy

The Web of Science (WoS) database by Clarivate Analytics was used to search and extract relevant scientific publications related to applying electrochemical processes for removing NSAIDs from wastewater. The chosen literature search strategies involved searching for keywords in the titles of papers, their abstracts, and author keywords (keyword search within the topic), specifically Topic 1 (electrochemical* OR electro-chemical* OR anodic oxidation* OR electro-membrane* OR EAOP* OR electrocatalytic* OR electro-oxidation* OR electrooxidation* OR electro-Fenton* OR photoelectro* OR photo-electro* OR electro-peroxone* OR “sono-electro*” OR sonoelectro* OR electrocoagulation*), Topic 2 (wastewater treatment*) and Topic 3 (“Non-steroidal anti-inflammatory drug*” OR “NSAID*” OR “aspirin” OR “Diclofenac” OR “Naproxen” OR “celecoxib” OR “etoricoxib” OR “flurbiprofen” OR “indometacin” OR “mefenamic acid” OR “meloxicam” OR “parecoxib” OR “piroxicam” OR “sulindac” OR “ketorolac trometamol” OR “Ketoprofen” OR “ibuprofen”), while excluding Topic 4 (“Coffee Bean Husk Biochars” OR “zeolite” OR “adsorption*” OR “photodegradation” OR “photocatalytic*” OR “photocatalyst*” OR “peroxymonosulfate” OR “spatial” OR “heterostructure photocatalyst” OR “heterogeneous Activator of Sodium Persulfate” OR “solar light activated photodegradation” OR “Peroxymonosulfate oxidation” OR “4-fluorophenol” OR “Peracetic Acid Oxidation Processes” OR “adsorption*” OR “enzymatic*” OR “biofilm*” OR “peracetic acid” OR “methyl orange” OR “magnetically separable”). The study included papers published over the past decade, covering the period from 1 January 2014 to 31 December 2024. Data were collected on 27 January 2024, encompassing all relevant publications within this timeframe.

Additionally, to clarify, through a comprehensive review of the literature and detailed reading of the papers retrieved through Topics 1, 2, and 3, it was established that some did not align with the topic, and it was necessary to exclude them, which was executed using Topic 4. Taking this into account, the WoS search yielded 93 scientific papers, 87 of which were research articles and six review articles. The English language is the predominant language, with only one paper published in Chinese. This dominant language use is unsurprising, since English is universally accepted as the language of scientific communication. Therefore, the analysis focused on 92 papers published exclusively in English, which were extracted for further analysis.

For visualizations and network analysis, we used CiteSpace (version 6.4.R1) and VOSviewer (version 1.6.18). CiteSpace, developed by Dr. Chaomei Chen [51], is a tool that specializes in the visualization and analysis of trends and patterns in the scientific literature. This study was employed to identify the most co-cited articles, journal co-citations, and the evolution of keywords over the past ten years. VOSviewer, on the other hand, was used for bibliometric analysis of research on the application of electrochemical technology for removing NSAIDs from wastewater, focusing on the analysis of co-authorship networks (countries, organizations, and authors), cited articles, and co-cited authors.

3. Results and Discussion

3.1. Research Metrics

To explore the first research question, which concerns the relevance and state of the literature on electrochemical-based technologies for removing NSAIDs from wastewater, the evolution of related articles within these fields was tracked using WoS data. An analysis of the annual and cumulative number of publications from 2014 to 2024 reveals a general increase in the number of published articles over time, although the growth has fluctuated, as illustrated in Figure 1. From 2014 to 2017, the number of published articles was relatively low, with fewer than five publications per year, which indicates the period of initiation of research on this topic. After 2017, interest in the field grew, leading to an increase in the number of papers published each year. However, this growth was not linear. Some years saw a significant rise in the number of publications, while others experienced a slight decline. The maximum of publishing activity occurred in 2021, which was the most productive year, with the highest number of published works during the observed decade. After 2021, a slight decline in publications was observed, reaching a level in 2024 slightly higher than that in 2017. This fluctuation indicates changes in research priorities, funding availability, or varying interest in the topic over the years. The narrow scope of the topic, which focuses specifically on electrochemical methods for removing NSAIDs from wastewater, helps explain the evolving trend in scientific publications, which clearly shows a growing interest in this research area, despite occasional fluctuations in publication activity. The majority of articles were published in the Engineering Environmental (26%) WoS category, with Environmental Sciences (23%) being the second most prominent, followed by Engineering Chemical (20%) (see Figure 2).

3.2. The Collaboration Network Analysis of Countries, Organizations, and Authors

Through the collaboration country analysis, the global network of collaborations was examined, key countries in scientific research were identified, and their influence on the international scientific community was clarified. The network map of international collaboration between countries using CiteSpace is illustrated in Figure 3. The 40 nodes represent countries with published papers in this field, and the density value of 0.1 reflects the relationships between them. The size of each node indicates the level of research productivity, while the pink ring surrounding each node represents its centrality in the collaboration network. The analysis revealed significant connectivity between China, India, Spain, France, and North Africa, with each other or other countries. China shows the largest node in the network, which indicates their greatest scientific article production (number of papers 32), suggesting that its scientific community is highly active and engaged in extensive international collaboration. Furthermore, China demonstrates a high betweenness centrality (centrality 0.68), indicating its crucial role as an intermediary, connecting different parts of the global research network. India and Spain (number of papers 9) have a higher number of publications than other countries, but their nodes are smaller than China’s, suggesting they are somewhat less prominent in global scientific production. Regarding degree, China (degree 15) has the most direct links to other countries, indicating that it collaborates with a broad range of nations. India and France (degrees 13 and 12) exhibit a lower degree but still maintain significant direct connections, reflecting stable collaboration with several key countries. These countries also show higher betweenness centrality (centrality 0.41 and 0.36), underscoring their importance as intermediaries between different research groups.

On the other hand, the results of the co-authorship analysis of organizations (see Supplementary Table S1) indicate that no single organization dominates the collaboration network. Among active organizations with publications on this topic, the frequency ranges from 1–3 publications. Additionally, centrality values are low for all organizations, suggesting that their role in mediating connections between different research groups is minimal. Moreover, neither frequency nor degree is particularly high, indicating limited international collaboration and a dispersed network without distinct hubs. Nevertheless, Chinese Academy of Sciences exhibits a slightly higher frequency compared to others (3 vs. 1). The Chinese Academy of Sciences and Centre National de la Recherche Scientifique (CNRS) also maintain a moderate number of direct connections (degree 17 and 9, respectively), reflecting stable but not highly intensive collaboration within the scientific community. Overall, the analysis suggests that the research community in this field operates within a decentralized model, with no single organization serving as a central connector. While collaborations exist, they are not highly intensive, which may indicate that this is still a developing research area or that institutions primarily operate independently.

The author’s co-authorship network analysis reveals the structure of collaboration among researchers in the observed field. Key metrics presented in Supplementary Table S2, such as the number of publications (documents), citations, and total link strength (TLS), provide insight into both research impact and author connectivity. As illustrated in Figure 4, the co-authorship network consists of smaller, weakly connected groups. The most productive authors—Torres, Wang, and Yu—each have four publications. Wang and Yu have the highest number of citations (416) and a low TLS value (17), indicating the significance of their work in the scientific field of electrochemical-based technologies for removing NSAIDs. However, the TLS value demonstrates their limited collaboration with other researchers. In contrast, Torres, despite having the same number of publications as the previous authors, has significantly fewer citations (79), suggesting that his work has had a lesser impact on the academic community. The weak links among authors may result from the fact that the research topic is still in its initial development phase, leading researchers to work individually or in small groups. Additionally, the narrow research area—electrochemical processes focused solely on NSAIDs, a small group of pharmaceuticals—limits the number of potential co-authors, naturally restricting collaboration. Furthermore, localized research efforts, where authors predominantly collaborate within national or regional frameworks, contribute to weaker international connections, ultimately lowering overall TLS values.

3.3. Most-Cited Articles

The network map obtained using VOSviewer software 1.6.18, presented in Figure 5, consists of the 77 most influential articles, each with at least five citations. The analysis reveals five significant clusters that highlight key research topics in the field of electrochemical technologies. These clusters not only represent the primary technologies applied in the electrochemical removal of NSAIDs from wastewater but also reflect dominant research interests and leading studies in this area.

The red cluster comprises articles related to the electro-peroxone (E-peroxone) process, emphasizing the synergistic effect of electrochemical and ozonization techniques for NSAID degradation. The green cluster focuses on the EF and electro-oxidation (EO) processes, recognized for their efficiency in generating hydroxyl radicals. The yellow cluster highlights research on BDD (boron-doped diamond) and carbon electrodes, valued for their stability and high performance. The blue cluster covers electrochemical AOPs involving photoelectro-Fenton, integrating photocatalysis for enhanced contaminant removal. Finally, the purple cluster includes studies on electrocoagulation and electromembrane processes, essential for the separation and removal of dissolved pollutants.

Table 1. The most cited articles.

Nb.	Document	Citations	Links	Title	Journal
1	Li et al. (2014) [52]	149	6	Degradation of the anti-inflammatory drug ibuprofen by electro-peroxone process	Water Research
2	Yao et al. (2018) [53]	139	2	Pilot-scale evaluation of micropollutant abatements by conventional ozonation, UV/O3, and an electro-peroxone process	Water Research
3	Yao et al. (2016) [54]	114	5	Removal of pharmaceuticals from secondary effluents by an electro-peroxone process	Water Research
4	Nadais et al. (2018) [55]	102	3	Bio-electro-Fenton process for the degradation of Non-Steroidal Anti-Inflammatory Drugs in wastewater	Chemical Engineering Journal
5	Loos et al. (2018) [56]	96	1	Electrochemical oxidation of key pharmaceuticals using a boron doped diamond electrode	Separation and Purification Technology
6	Bu et al. (2019) [57]	95	0	Unraveling different mechanisms of persulfate activation by graphite felt anode and cathode to destruct contaminants of emerging concern	Applied Catalysis B: Environmental
7	Yu et al. (2020) [58]	91	1	Hydrothermal synthesis of FeS2 as a highly efficient heterogeneous electro-Fenton catalyst to degrade diclofenac via molecular oxygen effects for Fe(II)/Fe(III) cycle	Separation and Purification Technology
8	Yu et al. (2019) [59]	79	2	Removal of diclofenac by three-dimensional electro-Fenton-persulfate (3D electro-Fenton-PS)	Chemosphere
9	Fernanda Garcia-Montoya et al. (2015) [60]	72	3	Application of electrochemical/BDD process for the treatment wastewater effluents containing pharmaceutical compounds	Journal of Industrial and Engineering Chemistry
10	Ouarda et al. (2018) [61]	70	2	Synthetic hospital wastewater treatment by coupling submerged membrane bioreactor and electrochemical advanced oxidation process: Kinetic study and toxicity assessment	Chemosphere

presents the 10 most cited articles identified by VOSviewer, serving as direct indicators of future research trends. Leading articles, such as Li (2014) and Yao (2018) (2016) [52,53,54], focus on the E-peroxone process, underlining its prominence in current research. Additionally, highly cited works by Nadais [55] and Loos [56] explore the bio-electro-Fenton (Bio-EF) process and electrode materials, further highlighting their critical role in electrochemical wastewater treatment.

4. Mechanisms and Recent Progress in Electrochemical Technologies for NSAIDs Removal

Based on the analysis of the most cited articles (Figure 5), E-peroxone, EF, and EO have become the most extensively researched electrochemical technologies for removing NSAIDs from wastewater.

Table 2. Publications on NSAIDs removal from wastewater by electrochemical-based technology during the period 2014–2024.

Technologies Type	NSAID	Experimental Conditions	Removal, %	References
EO	Diclofenac	Electrolyte: Synthetic pharmaceutical wastewater (NaCl or Na2SO4 and amine containing pharmaceuticals); Pt/Ti electrodes; Current density of 0.8 mA cm−2;	56.1%	[62]
EO	Diclofenac	Electrolyte: 0.5 M NaClO4; Anode: BDD; Cathode: stainless steel plate; Current density of 10, 15 i 20 mA cm−2;	100%	[63]
EO	Diclofenac	Electrolyte: 0.1 M NaOH; CNT, Pt/CNT and Ru/CNT modified electrodes;	48%	[64]
EO	Diclofenac	Electrolyte: Na2SO4; Anode: boron-doped diamond; Cathode: stainless steel; Current densities: 1.56 to 6.25 mA cm−2;	80%	[60]
EO	Ibuprofen	Electrolyte: synthetic hospital wastewater; Anode: BDD; Cathode: Nb; Current: 0.5 A	>97%	[61]
EO	Ibuprofen	Electrolyte: 0.1 M NaCl; Anode: glassy carbon, carbon fibre; Cathode: TiO2, stainless steel mesh; Voltage: 1.5 V and 2.5 V;	86%	[65]
EO	Naproxen	Electrolyte: 0.5 M Pb(NO3)2, 0.1 M HNO3, and 0.05 M NaF; Anode: graphite sheet; Cathode: stainless steel sheet; Current density: 7.5 mA cm−2;	98.5%	[66]
EO	Piroxicam	Electrolyte: 0.1 M Na2SO4; Anode: BDD; Cathode: Pt; Current density: 26.7 mA cm−2;	>98%	[67]
Bio-EO	Diclofenac	Electrolyte: wastewater sample and a mixed culture BDD anode and cathode; Current density of between 20 and 30 mA cm−2	73.1–96.6%	[68]
Bio-EO	Diclofenac	Electrolyte: synthetic wastewater; Anode: cylindrical aluminum; Cathode: stainless-steel mesh; Current density of 0.5 mA cm−2	70%	[68]
Bio-EO	Ibuprofen	Electrolyte: wastewater sample and a mixed culture; BDD anode and cathode; Current density of between 20 and 30 mA cm−2	79–100%	[68]
Bio-EO	Ketoprofen	Electrolyte: wastewater sample and a mixed culture BDD anode and cathode; Current density of between 20 and 30 mA cm−2;	72–96%	[68]
Bio-EO	Naproxen	Electrolyte: wastewater sample and a mixed culture BDD anode and cathode; Current density of between 20 and 30 mA cm−2	82–100%	[68]
Solar-EO	Diclofenac	Electrolyte: 50 mM of Na2SO4; Anode: BDD film on a niobium mesh substrate; Cathode: carbon-PTFE; Current density of 74 mA cm−2	>80%	[69]
Sono-EO	Ibuprofen	Electrolyte: syntetic solution and wastewater sample with IBU; AnodeTi/PbO2; Cathode:Ti; Current: 70 A at an open circuit potential of 40 V	90%	[70]
PEC	Naproxen	Electrolyte: 200 mM phosphate buffer pH 7.0; photoanode TiO2/CdS; UV Lamp: 9 W; Potential: +2.0 V	95.3%	[71]
PEC	Diclofenac	Electrolyte: 0.1 M Na2SO4; photoanode: N, S co-doped TiO2 nanocrystals on TiO2 nanotube arrays; 35 W Xenon lamp; Potential: 0.4 V	71.4%	[72]
PEC	Naproxen	Electrolyte: 70 mM NaCl, photoanode: ZnO/TiO2/Ag2Se; 36 W blue LED lamp; Potential: 1.0 V	100%	[73]
PEC	Ibuprofen	Electrolyte: water solutions, photoanode: BiOI/TNTAs; 100 W Hg lamp; Potential: 1.2 V	100%	[74]
EF	Diclofenac	Electrolyte: sodium persulfate addition 1.50 mM and the Fe0 addition 0.20 mM. Anode: titanium mesh; Cathode: carbon fiber; Voltage: 8 V	96.3%	[59]
EF	Diclofenac	Eletrolyte: synthetic pharmaceutical wastewater; Two parallel plate ferrous electrodes; power supply (30 V and 10 A), Current density of 58.47 mA cm−2	97.21%	[65]
EF	Diclofenac	Electrolyte: 0,05 M Na2SO4; Anode: Pt mesh; Cathode: GDE; Current density: 47.77 mA cm−2,	88%	[58]
EF	Diclofenac	Electrolyte: Na2SO4; Anode: boron-doped diamond; Cathode: stainless steel; Current densities: 1.56 to 6.25 mA cm−2;	50%	[60]
EF	Aspirin	Electrolyte: 0.05 M Na2SO4; Anode: Ti4O7; Cathode: carbon felt; Voltage: 8 V	100%	[75]
Bio-EF	Diclofenac	Electrolyte: 0.05 M Na2SO4 and 0.012 M sodium acetate solution; Anode: carbon brush; Cathode: graphite plate; Voltage: 0.3 V	87–97%	[55]
Bio-EF	Ibuprofen	Electrolyte: 0.05 M Na2SO4 and 0.012 M sodium acetate solution; Anode: carbon brush; Cathode: graphite plate Voltage: 0.3 V	80–86%	[55]
Bio-EF	Ketoprofen	Electrolyte: 0.05 M Na2SO4 and 0.012 M sodium acetate solution; Anode: carbon brush; Cathode: graphite plate; Voltage: 0.3 V	59–61%	[55]
Bio-EF	Naproxen	Electrolyte: 0.05 M Na2SO4 and 0.012 M sodium acetate solution Anode: carbon brush; Cathode: graphite plate; Voltage: 0.3 V	75–81%	[55]
PEF	Diclofenac	Electrolyte: 50 mM NaCl; Anode: Ti/IrO2 doped with SnO2; Cathode: carbon-felt; Current density of 6.92 mA cm−2;	>80%	[76]
SPEF	Diclofenac	Electrolyte: Na2SO4 or NaCl; Anode: BDD or IrO2; Cathode: gas diffusion or inert Ti; Current density: 3.25 mA cm−2; The electric potential remained between 3.5 and 4.0 V;	>80%	[77]
SPEF	Diclofenac	Electrolyte: 0.05 M Na2SO4; Anode: Ti/Ru0.3Ti0.7O2 plate; Cathode: carbon-PTFE ADC; Current density of 20 mA cm−2;	55%	[78]
SPEF	Diclofenac	Electrolyte: 0.05 M Na2SO4 and heptahydrated FeSO4; Anode: Ti/Ru0.3Ti0.7O2 plate; Cathode: carbon-PTFE ADC; Current densities: 10, 25, and 50 mA cm−2;	Almost 100%	[79]
SPEF	Ibuprofen	Electrolyte: 0.05 M Na2SO4; Anode: Ti/Ru0.3Ti0.7O2 plate; Cathode: PTFE ADC; Current density of 20 mA cm−2;	55%	[78]
SPEF	Salicylic acid	Electrolyte: 0. 05 M Na2SO4 and heptahydrated FeSO4; Anode: Ti/Ru0.3Ti0.7O2 plate; Cathode: carbon-PTFE ADC; Current densities: 10, 25, and 50 mA cm−2;	Almost 100%	[79]
E-peroxone	Diclofenac	Electrolyte: surface water; Anode: Pt plate; Cathode: carbon-PTFE; Applied currents: 10–50 mA;	>90%	[80]
E-peroxone	Diclofenac	Electrolyte: groundwater, surface water, and secondary wastewater; Anode: RuO2/IrO2 coated Ti plate; Cathode: carbon C-PTFE; Current: 50–200 mA;	>90%	[53]
E-peroxone	Ibuprofen	Electrolyte: 0.05 M Na2SO4; Anode: platinum-coated titanium (Pt-Ti); Cathode: Graphene-coated nickel foam (Gr-NF);Current of 400 mA;	87%	[81]
E-peroxone	Ibuprofen	Electrolyte: 0.05 M Na2SO4; Anode: Pt plate; Cathode: carbon-PTFE; Current of 300 mA;	100%	[52]
E-peroxone	Ibuprofen	Electrolyte: surface water; Anode: Pt; Cathode: carbon-PTFE; Currents: 10–50 mA;	90%	[80]
E-peroxone	Ibuprofen	Electrolyte: 0.05 M Na2SO4; Anode: Pt plate; Cathode: carbon-PTFE; Current 80 mA;	>90%	[54]
E-peroxone	Naproxen	Electrolyte: groundwater, surface water, and secondary wastewater; Anode: RuO2/IrO2 coated Ti plate; Cathode: carbon-PTFE; Current: 50–200 mA;	90%	[53]
EC	Diclofenac	Electrolyte: synthetic water samples and real water samples;Each electrode was made of aluminum;Current: 0.5 A;	14%	[62]
EC	Ibuprofen	Electrolyte: WWTP effluent collected from a secondary sedimentation tank Anode: Al; Cathode: stainless steel; Current densities: 5, 10 and 15 mA cm−2	<25%	[82]
EC	Ibuprofen	Electrolyte: synthetic water samples and real water samples; Each electrode was made of aluminum; Current density of 0.5 A;	44%	[83]
EC	Ibuprofen	Electrolyte: raw water; Anode: Al; Cathode: stainless steel; Current density: 15 mA cm−2;	58.6%	[84]
EC	Ketoprofen	Electrolyte: synthetic water samples and real water samples; Each electrode was made of aluminum; Current density of 0.5 A;	10%	[62]

provides a comparative overview of publications on NSAID removal from wastewater using electrochemical-based technology from 2014 to 2024.

Research initially concentrated on EO-based treatment, gradually shifting to EF, and more recently, hybrid approaches such as bio-EF and photo-electro-Fenton (PEF). To provide a complete overview of advancements in this area, we have summarized key studies on EO, EF, and emerging electrochemical combined technologies, emphasizing their mechanisms and recent progress in NSAID degradation.

Although the bibliometric analysis in this review focuses on publications from 2014 to 2024, selected earlier foundational studies are also included to provide essential background on the evolution of electrochemical technologies for NSAID removal.

4.1. Electrochemical Oxidation

The EO is a key technology widely used for the effective degradation of organic pollutants through electrochemical-based processes [85,86]. Organic pollutants that undergo electrochemical degradation include pharmaceuticals, pesticides, phenolic compounds, polycyclic aromatic hydrocarbons (PAHs), and other persistent organic pollutants [87,88,89,90,91,92,93,94]. Its mechanism encompasses both direct (through the transfer of electrons from organic pollutants adsorbed on the electrode surface to the anode) and indirect (by ROS generated at the anode) oxidation pathways, as presented in Figure 6.

According to the literature [95], the direct oxidation of organic pollutants is a rare phenomenon and generally exhibits low efficiency. In contrast, indirect electrochemical oxidation plays a dominant role in pollutant degradation, primarily occurring through hydroxyl radicals (•OH) generated at the anode surface via water oxidation. This environmentally sustainable approach is highly valued for wastewater treatment due to its reliance on electrons as “clean” reagents. Moreover, it is a safe and highly effective method for eliminating a broad spectrum of pollutants, including pharmaceutical residues such as NSAIDs.

The degradation efficiency of organic pollutants, including NSAIDs, is affected by the competition between their reaction with •OH and the oxygen evolution reaction (OER), which can reduce the overall oxidation efficiency. Studies [96] indicate that the reactivity of OH radicals is strongly influenced by their interaction with the electrode surface, which in turn depends on the nature of the anode material and its specific oxygen evolution potential (OEP). Comninellis [97] classified anodes into two primary categories: active anodes and non-active anodes. Active anodes are characterized by a low oxygen evolution potential, resulting in strong interactions between •OH and the electrode surface. When water undergoes oxidation, the generated OH radicals strongly adsorb onto the anode surface, forming metal-oxygen intermediates (M(•OH)). These adsorbed •OH can subsequently transform into chemisorbed “active oxygen” species, which include oxygen incorporated into the oxide lattice or superoxide (MO). Since these oxygen species have weaker oxidation potential compared to free OH radicals, they primarily facilitate the partial oxidation of organic pollutants, including NSAIDs, producing intermediate compounds such as short-chain carboxylic acids, aldehydes, and ketones. Non-active anodes, on the other hand, exhibit high oxidation power and possess a high OEP. Due to the weak interaction between the electrode surface and hydroxyl radicals, OH radicals desorb more easily, forming solvated hydroxyl radicals (•OH(aq)). These free •OH exhibit strong oxidation capacity, allowing them to efficiently degrade NSAIDs and other pharmaceutical residues, ultimately leading to their complete mineralization into carbon dioxide (CO₂) and water.

The selection of anode material plays a crucial role in determining the efficiency of electrochemical oxidation. Various types of anodes have been investigated for the degradation of NSAIDs via EO, such as Pt and boron-doped diamond (BDD) [56,98,99,100,101,102,103,104,105,106,107,108,109,110]. BDD is regarded as one of the most efficient anode materials due to its exceptional oxidation potential and high durability. Based on this fundamental knowledge, researchers initially conducted conventional EO treatment of NSAIDs, examining their degradation and mineralization efficiency, kinetics, and the influence of key parameters (such as solution pH, applied current or potential, electrolyte concentration, and type). They also identified by-products to establish the reaction mechanism. Research has primarily focused on BDD electrodes, comparing them with Pt anodes, and demonstrating that BDD exhibits superior oxidative properties and higher mineralization efficiency in NSAID removal [98]. Brillas [98] was among the first to investigate the electrochemical oxidation of NSAIDs using a BDD anode. In his 2005 study [98], he examined the degradation of paracetamol (1 g L⁻¹), examining the effects of applied current, temperature, and pH (2–12), in 0.05 M Na₂SO₄. The process is pH-independent due to the high concentration of •OH generated at the electrode surface. His findings demonstrated that BDD enables complete mineralization (T-35 °C, I = 450 mA, time 4 h) due to the high generation of hydroxyl radicals, whereas degradation on a Pt anode was significantly less efficient. The process followed pseudo-first-order kinetics, with higher current and temperature accelerating degradation, while increased initial paracetamol concentration slowed it down. Expanding on this research, Brillas explored diclofenac degradation in 2010 [99], showing that EO with BDD in a neutral buffer (pH 6.5) ensures complete removal, whereas Pt results in poor mineralization. Further studies, such as the work of Zhao et al. (2009) [100], reinforced these findings by analyzing diclofenac degradation on a BDD electrode in aqueous solutions. Their results indicated that EO effectively breaks down diclofenac (30 mg L⁻¹), achieving 72% mineralization after 4 h at 4.0 V. The study highlighted the role of applied potential and NaCl addition in the degradation process, revealing that chloride ions facilitate the formation of chlorinated byproducts like dichlorodiclofenac, temporarily increasing total organic carbon levels. Identified intermediates included 2,6-dichlorobenzenamine, 2,5-dihydroxybenzyl alcohol, benzoic acid, and 1-(2,6-dichlorocyclohexa-2,4-dienyl)indolin-2-one, which gradually disappeared as the reaction progressed, leaving small organic acids as final products. These insights contributed to a proposed degradation pathway, further demonstrating the effectiveness of EO with BDD for diclofenac removal. In 2010, Murugananthan et al. [101] investigated the mineralization of ketoprofen (KP) using EO with BDD and Pt electrodes. His study found that the degradation of ketoprofen was influenced by the electrolyte, pH, and applied current density, with the process primarily driven by the generation of hydroxyl radicals, peroxodisulfate (S₂O₈²⁻), and active chlorine species. While complete mineralization of ketoprofen was achieved with Na₂SO₄ as the supporting electrolyte, the presence of NaCl led to poor mineralization due to the formation of refractory chlorinated organic compounds. In 2013, Ambuludi et al. [102] investigated the electrochemical abatement of ibuprofen using anodic oxidation with both Pt and BDD anodes. The study showed that ibuprofen degradation followed pseudo-first-order kinetics, with BDD achieving higher removal rates due to the greater generation of •OH. The degradation process was not significantly affected by ibuprofen concentration but was influenced by the applied current and choice of supporting electrolyte, with NaCl enhancing the process. After 8 h of electrolysis, total organic carbon (TOC) removal ranged from 91% to 96%, and the primary intermediates identified were aliphatic acids, including oxalic, formic, and acetic acids.

Following these initial studies, research has continued over the past decade to optimize operating parameters, explore alternative electrode materials and the type of reactor, and address the formation of transformation by-products. The majority of the research focuses on coupling EO with other techniques, such as EF, which will be discussed in a separate section. While it is well established that the degradation of NSAIDs follows first-order kinetics and is primarily driven by hydroxyl radicals, later studies have further examined how factors like electrolyte composition, applied potential, and competing reactions influence the efficiency and selectivity of the process. For instance, Qui et al. [103] expanded on Brillas’ findings by systematically analyzing the effects of pH, electrolyte concentration, and chloride presence on diclofenac degradation using BDD anodes. Their study confirmed that •OH dominates the process, contributing 76.5% to total degradation, while sulfate radicals play a minor role. However, the study also highlighted the potential for unwanted by-product formation in the presence of chloride, leading to transient increases in TOC levels. Similarly, Loos et al. [56] investigated the performance of BDD electrodes in real hospital wastewater, reinforcing the superiority of BDD over Pt anodes. Their findings showed that while diclofenac degradation followed expected pseudo-first-order kinetics, persistent transformation products required extended treatment times to achieve full mineralization, underscoring the need for process optimization. Alternative electrode materials have also been explored. Iovino et al. [104] examined platinum-coated cylindrical electrodes and found that while they achieved high initial removal efficiencies, mineralization remained incomplete due to lower hydroxyl radical generation. In contrast, Ferreira’s work [64] with Ru/CNT and Pt/CNT electrodes revealed that electrode composition significantly influences degradation efficiency and by-product formation. Beyond diclofenac, studies have extended EO applications to other NSAIDs. García-Montoya et al. [60] demonstrated that EF with BDD electrode treatment enhances mineralization efficiency for paracetamol and DCF, achieving up to 80% TOC removal compared to conventional EO. Similarly, Feng’s work on naproxen degradation [105] revealed the formation of previously unreported toxic intermediates, emphasizing the need for toxicity assessments alongside degradation studies. Recent efforts have also focused on optimizing BDD electrode performance for large-scale applications. Corria’s study [63] identified an optimal current density range (10–20 mA cm⁻²) for diclofenac mineralization, balancing energy efficiency and degradation rates. His findings highlight the potential of EO as a viable wastewater treatment solution, if process parameters are carefully controlled to minimize by-product toxicity. These advancements confirm electrochemical oxidation, particularly with BDD electrodes, as a robust technique for NSAID removal. However, challenges remain, particularly in managing persistent intermediates and optimizing treatment conditions for real wastewater matrices. To assure complete mineralization and minimize toxicological impact, priority research over the last 10 years has focused on integrating EO with complementary treatment processes.

4.1.1. Bio-Electrooxidation (Bio-EO) Process

Bio-EO of NSAIDs offers a promising and sustainable solution for removing pharmaceutical contaminants from wastewater by combining the benefits of biological degradation and EO. One such approach, proposed by Jiménez-Bambague [68], combines a high-rate algal pond with an EO system utilizing BDD electrodes, demonstrating high efficiency in removing various NSAIDs. The effectiveness of NSAID removal followed this order: naproxen > fenofibric acid > ibuprofen > diclofenac > ketoprofen. Notably, integrating EO as a post-treatment significantly enhanced the degradation of these compounds, achieving removal rates exceeding 80% for anti-inflammatory drugs.

4.1.2. Sono-Electrooxidation (Sono-EO) Process

The combination of ultrasound and EO technology offers a promising solution for treating pharmaceutical and municipal wastewater by enhancing the degradation of NSAIDs. Ultrasound, through its cavitation effects, accelerates the mass transport rate and chemical reactions, while also mitigating electrode passivation and fouling [67]. Kouskouki’s study [67] demonstrated that coupling ultrasound with electrochemical oxidation using BDD electrodes significantly improved the degradation of piroxicam, achieving a synergy effect of 44.6%. Similarly, Tran’s research [70] using the same process achieved up to 90% ibuprofen removal. However, further cost analysis is necessary to assess the practical feasibility of this hybrid method on a larger scale.

4.1.3. Solar-Electrooxidation (Solar–EO) Process

The integration of an electrochemical device with a solar photoreactor significantly enhances the removal of micropollutants compared to traditional electrooxidative processes. This improvement is mainly due to the increased generation of oxidative species, which accelerate the degradation of various contaminants. In solar-assisted electrochemical treatments, ethylenediamine-N,N′-disuccinic acid (EDDS) plays a crucial role in keeping iron in solution during the process. However, its effectiveness is limited to the early stages of treatment, as EDDS degrades due to the electrochemical reactions. For wastewaters with high chloride concentrations, the use of Fe³⁺: EDDS can be avoided. In these cases, the Solar-EO process alone generates enough oxidizing agents to completely degrade micropollutants, including diclofenac, without the need for additional complexing agents. When combined with nanofiltration, Solar-EO demonstrates high efficiency, removing up to 80% of micropollutants. This makes it a promising method for wastewater treatment, producing high-quality effluent suitable for reuse. However, it is important to note that this hybrid process is not effective for removing dissolved organic carbon, which limits its use for reducing the total organic load [69].

4.1.4. EO and Ion Exchange Resins

The combination of EO and ion exchange resins has shown significant potential for the effective removal of NSAIDs, particularly Ibuprofen, from water, positioning it as a promising solution for future wastewater treatment applications. In the study conducted by Martins et al. [65], EO using carbon fiber electrodes was demonstrated to achieve a remarkable 71% degradation of ibuprofen within two hours. The reaction rate was notably enhanced by the addition of sodium chloride, which increased ionic conductivity and facilitated the generation of chlorine species, thereby almost doubling the reaction rate. Further improvements were observed when EO was paired with a mixed-bed ion exchange resin. This combined approach led to the near-complete removal of ibuprofen, bringing its concentration to levels close to undetectable. These results underscore the potential of integrating EO with ion exchange technology for the efficient elimination of pharmaceutical contaminants, marking a significant advancement in the development of sustainable and effective water treatment methods for micropollutants.

4.1.5. Photoelectrochemical (PEC) Process

PEC represents an AOP that effectively combines photocatalytic and EO techniques to enhance the removal efficiency of organic pollutants, including NSAIDs. This approach typically involves a semiconductor material—commonly titanium dioxide (TiO₂)—which, when exposed to ultraviolet or visible light, generates ROS, such as hydroxyl radicals. These highly reactive molecules are capable of initiating oxidation reactions that lead to the degradation of a wide spectrum of organic contaminants.

In PEC systems, an external bias voltage is applied to support the separation of photogenerated electron-hole pairs, thereby extending their lifetime and increasing the production of ROS. This synergy not only elevates the oxidative potential of the system but also accelerates the rate at which pharmaceutical residues are degraded [106].

Recent studies have emphasized the strong potential of PEC technology in removing NSAIDs from aqueous environments. For instance, PEC treatment of naproxen using a TiO₂/CdS photoanode under UV light (9 W) achieved a notable removal efficiency of 95.3% [71]. However, during this process, both toxic and less toxic transformation products may form. One study demonstrated that a ZnO/TiO₂/Ag₂Se thin-film composite electrode could completely degrade naproxen within 150 min, but this leads to the formation of naphthalenic by-products [73].

The practicality of PEC systems has been confirmed through various experimental setups. A PEC reactor employing N, S co-doped TiO₂ nanocrystals on TiO₂ nanotube arrays achieved a 71.4% reduction in diclofenac concentration under optimized pH conditions (pH 5) [72]. Another study utilized BiOI-deposited TiO₂ nanotube arrays (BiOI-TNTAs) and reported complete removal of ibuprofen within 120 min [74].

These findings not only validate the high effectiveness of PEC processes but also highlight their promise for broader application in wastewater treatment. Moreover, continuous innovations in this field, particularly in the synthesis of hybrid photocatalysts, are expanding the photo-response range into the visible spectrum, allowing for greater adaptability under variable lighting conditions [107]. This advancement increases the feasibility of integrating PEC systems into existing treatment infrastructures and enhances their resilience to fluctuations in contaminant loads and environmental factors.

4.2. Electro-Fenton

The EF method has emerged as a highly effective technology for the degradation of persistent organic pollutants, including non-steroidal anti-inflammatory drugs [93,108,109,110]. This electrochemical approach relies on the in situ generation of •OH within the bulk solution, making it a powerful alternative to direct electrochemical oxidation. The EF process is classified into different categories based on the method of Fenton reagent (H₂O₂ and Fe²⁺) production within the electrochemical system, as illustrated in Figure 7.

In the classic EF process, hydrogen peroxide (H₂O₂) is electrogenerated at a carbon-based cathode through oxygen reduction, while Fe²⁺ is externally added as a catalyst to initiate Fenton-like reactions. The resulting •OH effectively degrades NSAID molecules, facilitating their oxidation and potential mineralization. Several studies have demonstrated the efficiency of this method in breaking down NSAIDs into biodegradable intermediates, highlighting its applicability in pharmaceutical wastewater treatment.

The peroxy-coagulation (PC) process integrates the EF mechanism with iron-based coagulation. In this approach, H₂O₂ is electrogenerated at the cathode, while Fe²⁺ ions are released into the solution through anodic iron dissolution. This simultaneous production of reactive species enhances the oxidative degradation of NSAIDs while also promoting coagulation, which can aid in the removal of reaction by-products. The synergistic effect of oxidation and coagulation has been reported to improve NSAID mineralization efficiency, reducing the formation of toxic intermediates.

In contrast, the Fered–Fenton process involves the direct addition of Fenton’s reagent (a mixture of Fe²⁺ and H₂O₂) into the solution. Unlike conventional EF methods, this approach does not rely on the electrogeneration of H₂O₂ but rather utilizes external dosing. Although it remains an effective strategy for NSAID degradation, its reliance on chemical additives limits its sustainability compared to in situ electrochemical processes [111].

Another modification of the EF process is electrochemical peroxidation, which employs an iron anode for the electrochemical generation of Fe²⁺, while H₂O₂ is externally supplied. This method benefits from continuous Fe²⁺ regeneration at the anode, ensuring a sustained Fenton reaction without requiring external iron dosing. Studies have shown that electrochemical peroxidation can achieve high NSAID degradation rates, particularly when optimized anode materials are employed.

The choice of cathode material significantly influences the efficiency of EF processes. While mercury electrodes were historically used due to their high electrocatalytic activity, their toxicity has led to a shift toward carbon-based cathodes such as carbon black, carbon sponge, carbon nanotubes, active carbon fiber, carbon felt, and graphene oxide [112,113,114,115,116]. These materials exhibit excellent stability, high surface area, and strong catalytic properties for H₂O₂ production, making them suitable for large-scale applications. In addition, carbon materials provide numerous advantages, including structural flexibility, accessibility, environmental friendliness, and low cost.

Therefore, the EF processes can be divided into two categories based on the catalyst’s physical characteristics: homogeneous EF (homo-EF) and heterogeneous EF (hetero-EF). In homo-EF, iron is used in its soluble form as the catalyst, while in hetero-EF, solid catalysts provide the iron source [117,118]. Although homo-EF remains widely applied for wastewater treatment, hetero-EF is gaining attention as a more efficient method The hetero-EF process offers significant advantages by effectively overcoming pH range limitations, allowing easier separation of the catalyst from the liquid phase after treatment, reducing or eliminating iron sludge formation, and enhancing the durability and consistency of the catalyst [119,120]. The development of cathodes has enhanced H₂O₂ production efficiency, improving the overall oxidation capacity of the system.

Recent advancements in EF-based NSAID degradation focus on cathode modification, catalyst and process optimization, and process integration with complementary treatment technologies. Muzenda [75] proposed a method to improve heterogeneous EF water treatment by immobilizing magnetite nanoparticles, synthesized through coprecipitation with varying Fe²⁺/Fe³⁺ molar ratios, on a carbon felt cathode using magnetic bars. The approach enhanced catalyst stability and efficiency, with a 23% improvement in aspirin degradation and complete degradation achieved within 140 min at the optimal Fe²⁺/Fe³⁺ ratio of 1:4. The magnetized magnetite catalyst was reusable for up to 10 cycles, demonstrating its potential to prevent catalyst leaching in EF processes. Yu’s study [58] demonstrated that hydrothermally synthesized FeS₂ effectively catalyzes H₂O₂ decomposition, improving diclofenac sodium degradation across a wide pH range (3–9) in a heterogeneous EF process. The Pyrite-EF method showed superior performance compared to traditional EF, with enhanced degradation rates due to the activation of molecular oxygen and increased surface-bound ferrous ions on FeS₂. Also, toxicity testing revealed that the treated solution was non-toxic, confirming the effectiveness of the Pyrite-EF process in removing DCF from wastewater.

Additionally, hybrid approaches that combine EF with other electrochemical AOPs, such as PEF and sono-electro-Fenton, have been explored to further enhance degradation rates and minimize the formation of harmful by-products.

4.2.1. The Bio-Electro-Fenton

The Bio-EF process is an advanced electrochemical treatment method that integrates biological degradation with the Fenton reaction to enhance the removal of pharmaceutical contaminants, particularly NSAIDs, from wastewater. This hybrid approach leverages microbial activity to facilitate in situ production of Fenton’s reagent (H₂O₂ and Fe²⁺), thereby increasing the availability of •OH for the oxidative breakdown of persistent pollutants. A key advantage of the Bio-EF process over conventional EF treatment lies in its reduced reliance on external chemical inputs. The microbial community within the system contributes to continuous Fe²⁺ regeneration, while also promoting biodegradation of intermediate oxidation products, resulting in a more efficient and environmentally friendly treatment [121,122].

Author Nadais [55] investigated the Bio-EF process for the degradation of NSAIDs, focusing on the microbial electrolysis cell (MEC) system for treating low-concentration NSAIDs in municipal wastewater. The study focused on an MEC-based system designed to treat low concentrations of NSAIDs. The system demonstrated the ability to efficiently degrade various NSAIDs, with removal efficiencies ranging from 59% to 61% for Ketoprofen, 87% to 97% for Diclofenac, 80% to 86% for Ibuprofen, and 75% to 81% for Naproxen after 5 h of reaction time. The process was influenced by several factors, including pH, Fe²⁺ concentration, airflow rate, initial NSAID concentration, and the applied voltage. The results indicated that the Bio-EF system holds promise as a viable and sustainable alternative for treating wastewater contaminated with persistent micropollutants. Compared to traditional EF treatments, this system offers improved pollutant removal rates and reduces the toxicity of residual by-products.

4.2.2. Photo-Electro-Fenton Process and Solar Photo-Electro-Fenton

PEF process is an advanced oxidation technology that enhances conventional EF treatment by incorporating light irradiation, typically in the form of ultraviolet (UV) or visible light exposure [123,124]. This hybrid approach significantly improves pollutant degradation efficiency through additional photochemical reactions that regenerate Fe²⁺, promote the breakdown of persistent contaminants, and accelerate the mineralization of organic pollutants such as NSAIDs.

One of the key advantages of the PEF process over standard EF treatment is its ability to continuously regenerate Fe²⁺ via photoreduction of Fe³⁺ under UV or solar irradiation. This prevents the accumulation of Fe³⁺ in the reaction medium, maintaining optimal Fenton activity and increasing the yield of •OH. Additionally, photodegradation of intermediates formed during EF oxidation further enhances treatment efficiency, reducing the formation of toxic by-products.

In the study conducted by Martínez-Pachón [76], the PEF process was evaluated for the removal of diclofenac from municipal wastewater effluents. The findings revealed that the combination of electrochemically produced H₂O₂ and UV-assisted regeneration of Fe²⁺ played a key role in significantly accelerating the degradation of diclofenac, offering improved performance over traditional EF methods. Optimized conditions in the PEF system resulted in near-total mineralization of diclofenac while maintaining lower energy consumption. Moreover, this treatment effectively reduced bacterial populations, including pathogenic species, thereby minimizing the environmental threat posed by diclofenac contamination. This research underscores the potential of the PEF process as a viable solution for treating wastewater contaminated with diclofenac, offering dual benefits by addressing both pharmaceutical and microbial pollutants efficiently.

The solar photo-electro-Fenton (SPEF) process is an enhanced version of the traditional PEF method, which utilizes solar energy as the primary light source. This makes the process more sustainable compared to the conventional PEF, which relies on artificial UV or visible light. By leveraging natural sunlight, SPEF reduces energy consumption and environmental impact while promoting the regeneration of Fe²⁺ ions, essential for •OH production. As a result, the SPEF process provides an eco-friendly and cost-effective alternative for degrading pollutants like NSAIDs, achieving similar degradation rates to PEF but with lower energy demands [78,125].

Several studies have explored the effectiveness of the SPEF process in degrading NSAIDs in wastewater. For instance, Bugueño-Carrasco [79] investigated the removal of diclofenac and salicylic acid using SPEF. Their results showed that the process successfully degraded these pharmaceuticals within the first 10 min, achieving an impressive 99.2% TOC removal after 100 min of treatment. The degradation followed pseudo-first-order kinetics, with energy consumption recorded at 534.23 kWh (kgTOC)⁻¹ and 7.15 kWh m⁻³, indicating that the SPEF process is highly efficient in terms of energy use. This makes it a promising and cost-effective solution for treating NSAID contamination in wastewater, particularly in real-world applications. Campos [78] also explored the potential of SPEF for degrading NSAIDs, focusing on diclofenac and ibuprofen. Their study demonstrated that the process could reduce the concentration of these pharmaceuticals by over 90% in just one hour. The treatment was conducted in a solar electrochemical raceway pond reactor (SEC-RPR) under optimized conditions, which included a current density of 20 mA cm², Na₂SO₄ at 0.05 mM, Fe²⁺ at 0.05 mM, and a pH of 3. In addition to significantly lowering the organic load in wastewater, the SPEF process also promotes the mineralization of pollutants, making it a sustainable solution for addressing NSAID pollution. In a similar vein, Manrique-Losada’s [77] research further investigated the degradation of various pharmaceuticals, including acetaminophen, diclofenac, ciprofloxacin, and sulfamethoxazole, using the SPEF process. The study found that the BDD anode system achieved about 49% degradation, while the IrO₂ anode system in NaCl resulted in a higher degradation rate of around 99%. Manrique-Losada [77] also examined the role of copoazu (COPE), an Amazonian fruit extract, in enhancing the SPEF process. The addition of COPE improved the process’s efficiency, particularly by helping maintain iron in solution at near-neutral pH. COPE, rich in polyphenols and citric acid, acted as a natural complexing agent that facilitated the regeneration of ferrous ions and supported the catalytic cycle of iron. This led to a significant improvement in pharmaceutical removal, with around 70% degradation observed. The study highlighted the potential of integrating COPE into the SPEF system, positioning it as an effective strategy for enhancing pharmaceutical degradation in wastewater treatment. Together, these studies demonstrate the versatility and efficiency of the SPEF process in addressing NSAID contamination in wastewater. Whether through optimizing process conditions or incorporating natural additives like COPE, the SPEF method shows great promise as a sustainable and energy-efficient solution for the degradation of pharmaceutical pollutants.

From an environmental perspective, PEF and SPEF has been recognized as a promising alternative to conventional wastewater treatment methods due to its ability to achieve near-complete mineralization of NSAIDs without the excessive use of chemical reagents. However, challenges such as the optimization of irradiation conditions, scaling up reactor configurations, and minimizing secondary waste production remain critical areas of ongoing research.

Bibliometric trends indicate growing interest in PEF and SPEF applications for pharmaceutical wastewater treatment, with recent studies focusing on improving reactor designs, exploring alternative light sources, and integrating PEF with other AOPs. Future research directions are expected to emphasize further energy optimization, the development of novel photoactive materials, and the assessment of long-term environmental impacts to enhance the practical applicability of PEF and SPEF technology.

4.3. The Electro-Peroxone Process

The E-peroxone process has emerged as a particularly effective electrochemical method for the removal of pharmaceutical pollutants from wastewater, including NSAIDs. This technology combines electrochemically generated H₂O₂ with ozone to enhance the oxidation of persistent organic compounds, such as NSAIDs [126,127,128]. The mechanism of this process is based on the enhanced transformation of ozone into highly reactive hydroxyl radicals, which possess a strong oxidative capacity, enabling the effective degradation of NSAIDs. Compared to conventional ozonation, the E-peroxone process demonstrates higher efficiency in removing pharmaceutical residues due to the synergistic action of H₂O₂ and ozone, resulting in faster and more complete degradation of pollutants. Research indicates that this process not only increases the efficiency of NSAID removal but also reduces energy consumption compared to standard AOPs [129,130,131].

Building on this, studies have highlighted the broader potential of the E-peroxone process. For instance, Li [52] postulated that the combination of in-situ H₂O₂ generation through electrolysis with ozone significantly accelerates the degradation of pharmaceuticals like diclofenac and ibuprofen. The E-peroxone process achieves the complete breakdown of ibuprofen in just 5–15 min, a remarkable improvement compared to traditional ozonation (about 30 min) and electrolysis (several hours). The process is driven by hydroxyl radicals, which effectively break down the drugs and mineralize any toxic byproducts. Moreover, the effluent from the E-peroxone treatment showed much lower toxicity, with only 5% inhibition of bioluminescence in Vibrio fischeri, compared to 22% for ozonation and 88% for electrolysis. These results demonstrate that E-peroxone is not only efficient but also environmentally safer. Further examination of the process has shown that in-situ H₂O₂ and •OH production are essential for enhancing the degradation of pharmaceuticals. A chemical kinetic model proposed by Wang [80], used in the analysis, helped simulate the removal of NSAIDs such as diclofenac and ibuprofen from various water sources, including surface water, secondary wastewater effluent, and groundwater. This model successfully predicted degradation rates and allowed for the optimization of ozone doses, making the E-peroxone process a cost-effective and energy-efficient method for wastewater treatment. Yao [53] compared the E-peroxone method to traditional ozonation and UV/O₃ processes, finding that it is more effective in reducing highly reactive micropollutants like diclofenac and naproxen by over 90%. For more ozone-resistant compounds such as ibuprofen and chloramphenicol, the E-peroxone process increased removal efficiency by 15–43%, while consuming 10–53% less energy than conventional ozonation and significantly reducing bromate formation. These results make it a promising, energy-efficient alternative for micropollutant removal and bromate control in water treatment. Additional research has shown that the E-peroxone process can be especially effective in situations where traditional purification methods are inadequate for eliminating pharmaceutical contaminants. For example, Yao [54] observed that the E-peroxone process significantly improved the degradation of ozone-resistant drugs like ibuprofen by electrochemically producing H₂O₂, which then generates hydroxyl radicals. This approach enhanced the removal rate of these substances by approximately 40–170% compared to conventional ozonation, with the most noticeable improvements occurring in secondary effluents containing lower levels of effluent organic matter (EfOM). Additionally, the E-peroxone process reduced the time and energy required to remove 90% of pharmaceuticals from the effluent, making it a more energy-efficient option than traditional methods. However, higher concentrations of EfOM in the effluent can hinder the process, as it can scavenge the hydroxyl radicals, diminishing the effectiveness of the E-peroxone process, especially in effluents with higher organic content. Srinivasan’s [81] investigation into the E-peroxone process demonstrated the effectiveness of a novel graphene-coated nickel foam (Gr-NF) electrode for removing ibuprofen. The Gr-NF electrode outperformed the Reticulated Vitreous Carbon (RVC) electrode by generating 1.7 times more •OH and achieving 87.0% ibuprofen mineralization in 60 min. This system also showed significant performance in treating real pharmaceutical wastewater, including reductions in total organic carbon, disinfection, decolorization, and turbidity, positioning the Gr-NF electrode as a more efficient and stable option for wastewater treatment.

The advantages of the E-peroxone process include the potential for integration into existing wastewater treatment systems, reduced generation of toxic by-products, and optimized chemical consumption. However, challenges such as the optimization of operational parameters (e.g., pH, ozone, and H₂O₂ concentrations, electrical current) and the economic feasibility of this approach remain subjects of ongoing research. Further bibliometric analysis shows a growing interest from the scientific community in the application of the E-peroxone process for wastewater treatment, indicating its potential as a sustainable and effective technology for removing pharmaceutical pollutants, including NSAIDs.

Recent trends in E-peroxone research suggest its expanding application not only in the treatment of pharmaceutical contaminants but also in the removal of other persistent organic compounds. Bibliometric analysis of the available literature reveals a significant increase in publications on this topic over the past decade, with a particular focus on process optimization, by-product reduction, and improved energy efficiency. Further research is expected to contribute to a better understanding of the degradation mechanisms of NSAIDs through the E-peroxone process and enable its broader application in wastewater treatment plants.

4.4. Environmental Implications and Potential Applications

The presence of NSAIDs in aquatic environments poses a growing environmental concern due to their persistence, potential toxicity to aquatic organisms, and ability to disrupt ecosystems even at low concentrations. Conventional wastewater treatment plants are often ineffective in removing these micropollutants, leading to their accumulation in surface and groundwater. Electrochemical-based technologies offer a promising solution due to their high degradation efficiency, minimal chemical use, and potential for complete mineralization of pharmaceutical compounds. These technologies align with the principles of green chemistry and can be integrated into existing wastewater treatment infrastructure. Potential applications include the treatment of effluents from hospitals and pharmaceutical industries, as well as the polishing step in municipal wastewater treatment to ensure safer discharge or water reuse.

5. Conclusions and Future Directions

In the past decade, electrochemical-based methods have gained significant global attention for their potential in environmental remediation, particularly for treating wastewater contaminated with NSAIDs. Research in this field has primarily focused on three key technologies: E-peroxone, EF, and electrochemical oxidation. Initially, EO-based treatments received the most attention, but over time, research has gradually shifted towards EF and E-peroxone. There is also a growing interest in improving efficiency and integrating electrochemical techniques with other remediation technologies.

China has contributed the majority of research in this field, while developing countries have played a comparatively smaller role. Notably, the Chinese Academy of Sciences has published the highest number of studies on this topic.

Despite significant advancements, several challenges persist in electrochemical-based technologies for the treatment of pharmaceutical pollutants like NSAIDs, including: (1) ensuring electrode stability and durability, (2) reducing energy consumption, (3) minimizing the formation of toxic byproducts, (4) scaling up from laboratory to industrial applications, (5) integrating electrochemical processes with other treatment methods, (6) improving economic viability, and (7) ensuring environmental and operational sustainability.

To enhance the efficiency, sustainability, and practical applicability of electrochemical technology for NSAID removal from wastewater, future research should focus on the following key areas: (1) development of innovative electrode materials; (2) enhancement of electrochemical reaction mechanisms; (3) reduction of energy demand and integration of renewable energy sources; (4) prevention of toxic byproduct formation and ensuring complete degradation; (5) scaling up electrochemical systems for real-world applications; (6) integration of electrochemical treatment with other technologies; (7) ensuring environmental and economic sustainability.

This review adds scientific value by providing a comprehensive bibliometric and content-based analysis that highlights key technological transitions, leading contributors, and thematic research clusters. By identifying current gaps, emerging trends, and future priorities, it offers a structured overview that can support more targeted, efficient, and sustainable development of electrochemical technologies for pharmaceutical wastewater treatment.