Hybrid Solar Photoelectro-Fenton and Ozone Processes for the Sustainable Removal of COVID-19 Pharmaceutical Contaminants

Abstract

This study explores a hybrid advanced electrochemical oxidation process (EAOP) intensified by solar irradiation and ozone for the treatment of wastewater containing COVID-19-related pharmaceuticals. Pilot-scale trials were performed in a 30 L compound parabolic collector (CPC)-type photoreactor with a boron-doped diamond (BDD–BDD) electrode configuration. Under optimal conditions (50 mg L⁻¹ paracetamol, 0.05 M Na₂SO₄, 0.50 mM Fe²⁺, pH 3.0, and 60 mA cm⁻²), the solar photoelectro-Fenton (SPEF) process achieved 78% chemical oxygen demand (COD) reduction within 90 min, with catechol and phenol detected as the main aromatic intermediates. When applied to a four-drug mixture (dexamethasone, paracetamol, amoxicillin, and azithromycin), the solar photoelectro-Fenton (SPEF–ozone (O₃)) system reached 60% degradation and 41% COD removal under solar conditions. The results highlight the synergistic effect of ozone and solar energy in enhancing the electrochemical oxidation process (EAOP) performance and demonstrate the potential of these processes for scalable and sustainable removal of pharmaceutical contaminants from wastewater.

1. Introduction

In December 2019, a novel coronavirus disease (COVID-19), caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), rapidly spread worldwide [1]. Since the emergence of COVID-19, the most important challenge for researchers and healthcare professionals has been to find the best treatment options for the new disease. In this regard, the World Health Organization published general guidelines to deal with the SARS-COV-2 disease, which included palliative care [2,3]. To combat this threat, anti-inflammatory drugs have emerged as a symptomatic treatment option for COVID-19. The use of anti-inflammatory drugs such as paracetamol and ibuprofen is currently considered one of the most effective approaches for the treatment of the symptoms of COVID-19 [4,5]. In this regard, related studies have shown that up to 85% of COVID-19 patients develop fever, and paracetamol is commonly used as the first treatment [6].

Despite the high importance of these drugs for COVID-19 patients, one aspect that must be considered is the environmental impact that these chemical substances are causing upon disposal. In this way, after being administered to patients, a variable proportion of these chemicals have been detected in effluents, wastewater plants, and even in surface and underground water bodies that, at some point in time, are recharged with treated water [7]. The most frequently employed cocktail of drugs used for the symptomatic treatment of COVID-19 includes different medications that depend on the location in which the medical treatment takes place. In this regard,

Table 1. CAS Registry Number, Molecular Formula, and Molecular Weight, and Water Solubility of Some Drugs Used During the COVID-19 Pandemic.

Drug	CAS	Molecular Formula	Molecular Weight	Solubility in Water (mg (100 mL)−1)
Paracetamol	103-90-2	C8H9NO2	151.16 g mol−1	1.4
Dexamethasone	50-02-2	C22H29FO5	392.46 g mol−1	1000
Azithromycin	83905-01-05	C38H72N2O12	749 g mol−1	514
Amoxicillin	26787-78-0	C16H19N3O5S	365.4 gmol−1	10.7

summarizes some of the most commonly used drugs whose consumption became popular during the COVID-19 pandemic, along with some of their physicochemical properties [8]. Further information is provided in Figures S1–S3.

The presence of pharmaceuticals in the environment, such as paracetamol, is mainly due to their incomplete removal during wastewater treatment and inadequate management, leading to their persistence in treated effluents and eventual discharge into surface waters.

According to previous studies, the concentration of paracetamol in natural water bodies varies widely around the world due to factors such as local consumption habits, the effectiveness of wastewater treatment systems, and various environmental conditions [9,10]. The problem arises since some chemical substances, such as hydroquinone, p-aminophenol, n-acetyl-benzoquinone, and 1,4-benzoquinone, are often intermediates with high liver toxicity. In this context, paracetamol concentrations ranging from 1 to 100 μg L⁻¹ have been detected in wastewater in countries such as Korea, Spain, and the Western Balkans, raising concerns about the potential ecological impacts on aquatic life, long-term accumulation, emergence of resistance, and human exposure through water consumption. Despite this situation, many countries lack specific regulations on permitted levels of paracetamol discharge, particularly in areas close to pharmaceutical plants [11].

During the COVID-19 pandemic, efforts focused on mitigating the number of fatalities and trying to provide early treatment to individuals in “at-risk groups”. In 2020, during the health crisis, the use of different non-antiviral drugs also became popular [12], and their presence and that of their related by-products have become an important environmental issue. In this context, over the previous three decades, Advanced Oxidation Processes (AOPs) have been identified as options for removing organic compounds from wastewater and water bodies. These processes include a variety of chemical, photochemical, electrochemical, and photoelectrochemical methods where organic compounds are oxidized and frequently mineralized due to the attack of reactive oxygen species (ROS) [13,14].

Electrochemical Advanced Oxidation Processes (EAOPs) constitute a subgroup within advanced oxidation processes that have demonstrated high efficiency in removing persistent and toxic pollutants from wastewater, mainly due to their ability to generate strong oxidizing species under relatively mild operating conditions [15]. Among them, anodic oxidation (AO) represents the most straightforward approach, in which organic contaminants are degraded through direct electron transfer or via hydroxyl radicals (M(^•OH)) weakly adsorbed on the surface of the anode (M), as expressed in Equation (1) [16]. Common electrode materials used for this purpose are boron-doped diamond (BDD) and dimensionally stable anodes (DSA). Another frequently applied strategy is the electro-Fenton (EF) process, which involves the cathodic generation of hydrogen peroxide (H₂O₂) through Equation (2), followed by its reaction with added Fe²⁺ ions to produce hydroxyl radicals (^•OH) via the classical Fenton reaction (Equation (3)) [17,18]. The Fe²⁺ consumed in this process can be continuously regenerated by cathodic reduction of Fe³⁺, according to Equation (4). Contaminants are thus eliminated by a combination of direct anodic oxidation, mediated oxidation through M(^•OH), and homogeneous ^•OH attack. Nevertheless, the EF process often achieves limited mineralization due to the persistence of stable Fe(III)-carboxylate complexes (Fe(OOCR)²⁺), which are poorly reactive towards ^•OH [19,20]. To overcome this limitation, irradiation with UV light has been introduced, leading to the photoelectro-Fenton (PEF) process, which significantly enhances mineralization efficiency [21]. In particular, the use of sunlight as an irradiation source (solar PEF, SPEF) provides an attractive and sustainable option, since it promotes the photolysis of Fe(OH)²⁺ complexes (Equation (5)) to regenerate Fe²⁺ and produce additional ^•OH, as well as the photodecomposition of Fe(III)-carboxylates (Equation (6)), thereby improving overall pollutant removal.

$$\mathrm{M}+{\mathrm{H}}_2\mathrm{O}\to \mathrm{M}\left({}^{•}\mathrm{O}\mathrm{H}\right)+{\mathrm{H}}^{+}+{\mathrm{e}}^{-}$$

(1)

$${\mathrm{O}}_2+2{\mathrm{H}}^{+}+2{\mathrm{e}}^{-}\to {\mathrm{H}}_2{\mathrm{O}}_2$$

(2)

$${\mathrm{F}\mathrm{e}}^{2+}+{\mathrm{H}}_2{\mathrm{O}}_2\to {\mathrm{F}\mathrm{e}}^{3+}+{}^{•}\mathrm{O}\mathrm{H}+{\mathrm{O}\mathrm{H}}^{-}$$

(3)

$${\mathrm{F}\mathrm{e}}^{3+}+{\mathrm{e}}^{-}\to {\mathrm{F}\mathrm{e}}^{2+}$$

(4)

$$\mathrm{F}\mathrm{e}{\left(\mathrm{O}\mathrm{H}\right)}^{2+}+\mathrm{h}\mathrm{v}\to {\mathrm{F}\mathrm{e}}^{2+}+{}^{•}\mathrm{O}\mathrm{H}$$

(5)

$$\mathrm{F}\mathrm{e}{\left(\mathrm{O}\mathrm{O}\mathrm{C}\mathrm{R}\right)}^{2+}+\mathrm{h}\mathrm{v}\to {\mathrm{F}\mathrm{e}}^{2+}+{\mathrm{C}\mathrm{O}}_2+{\mathrm{R}}^{•}$$

(6)

In contrast, it is widely recognized that the application of ozone alone often results in a relatively slow degradation of pollutants in wastewater, mainly because this process produces limited amounts of hydroxyl radicals (^•OH), which are far more powerful oxidants [22]. However, when ozone treatment is combined with ultraviolet (UV) irradiation, the oxidative efficiency of the system is markedly improved. In aqueous solution, ozone exhibits a maximum molar absorption coefficient (εmax) of 3600 L·mol⁻¹·cm⁻¹ at a wavelength of 253.7 nm. Under these conditions, ozone molecules can be photoactivated by solar UV light, enabling their reaction with water to generate hydrogen peroxide (H₂O₂) according to Equation (7). Subsequently, H₂O₂ can undergo reduction, giving rise to homogeneous hydroxyl radicals (^•OH) as described by Equation (8) [23,24].

$${\begin{array}{c}\mathrm{O}\end{array}}_3+{\mathrm{H}}_2\mathrm{O}+\mathrm{h}\mathrm{v}\to {\mathrm{H}}_2{\mathrm{O}}_2+{\mathrm{O}}_2$$

(7)

$${\mathrm{H}}_2{\mathrm{O}}_2+{\mathrm{O}}_2\to 2{}^{•}\mathrm{O}\mathrm{H}+3{\mathrm{O}}_2$$

(8)

The purpose of this research is to establish an effective solar photoelectro-Fenton system coupled with ozone (SPEF/O₃) for the treatment of wastewater contaminated with pharmaceuticals commonly prescribed during the symptomatic management of COVID-19. Since wastewater containing these compounds represents a complex chemical matrix, a methodological approach was employed not only to assess the overall efficiency of the process but also to identify and characterize the main transformation products. Previous studies have already demonstrated the feasibility of using the solar photoelectro-Fenton process with CPC-type photoreactors for the degradation of industrial anilines [25]. Building on this knowledge, the present work first evaluates paracetamol as a model contaminant under SPEF conditions. Subsequently, the comparative removal of a representative drug mixture—dexamethasone, paracetamol, azithromycin, and amoxicillin—was investigated by both O₃/sunlight and SPEF/O₃ processes. The selection of these four pharmaceuticals responds to their massive use during the COVID-19 pandemic, which led to their recognition as emerging pollutants of major environmental concern. The experimental assays were carried out in a pilot setup consisting of a filter-press electrochemical cell with BDD/BDD electrodes connected to a CPC-type photoreactor and integrated with an ozone generator. In addition, the abatement of chemical oxygen demand (COD) and the formation of key intermediates were quantified to evaluate process performance.

This research is framed within a pressing global challenge: the post-pandemic contamination caused by the extensive use of pharmaceuticals. The persistent detection of these compounds in aquatic ecosystems has been documented in several countries, including Mexico, the site of the present study. To the best of our knowledge, this is the first report in Latin America that evaluates the combined application of solar photoelectro-Fenton (SPEF) and ozonation for the removal of post-COVID-19 pharmaceuticals at a pilot scale under natural solar irradiation.

The technological approach proposed here addresses an emerging environmental problem through a sustainable strategy, as it relies on solar energy—an abundant, free, and renewable resource. Furthermore, the system is based on commercially available components (BDD electrodes, ozone generator, and CPC photoreactors), which enhances its potential for replication in developing countries. This configuration demonstrates technical feasibility for large-scale applications, enabling the simultaneous degradation of diverse pharmaceuticals—such as antibiotics, anti-inflammatory agents, and corticosteroids—in complex water matrices. Such integrative treatment represents a significant step forward compared to prior studies that have mainly focused on the degradation of single compounds.

2. Experimental Section

2.1. Chemicals

Commercial dexamethasone, paracetamol, amoxicillin, and azithromycin were obtained from a drug store in Mexico (Farmacias del Ahorro, Mexico City, Mexico). Analytical grade sodium sulfate (Na₂SO₄), used as a supporting electrolyte, was purchased from Karal (Gto, México). Analytical grade heptahydrated iron (II) sulfate (FeSO₄·7H₂O) for Fenton-based processes and analytical grade sulfuric acid for adjusting the solution pH to 3.0 were obtained from J.T. Baker^TM (Radnor, PA, USA). All other chemicals used for high-performance liquid chromatography (HPLC) were purchased from Sigma-Aldrich (Saint Louis, MO, USA). The solutions used for this work were prepared using raw water, whose physicochemical characteristics are shown in

Table 2. Physicochemical Characterization of the Raw Water Used in this Study.

Parameter	Value
Total dissolved solids (TDS)	232 mg L−1
Temperature	23–25.5 °C
Salinity	0.042%
Specific density	1.100
pH	7.1
Oxidation-Reduction Potential (ORP)	143–154 mV
Electrical conductivity (EC)	480 µS cm−1
Total hardness	78.05 mg L−1
Hardness to Mg	19.5 mg L−1
Hardness to Ca	58.1 mg L−1

.

2.2. Electrochemical Set-Up

Figure 1 depicts the batch SPEF/O₃ pilot plant employed in this study, consisting of the following components: (1) a filter-press electrochemical cell, (2) a CPC-type photoreactor, (3) an ozone generator, (4) a DC power supply, (5) a storage reservoir, and (6) a centrifugal pump. The system was specifically configured to treat 30 L of aqueous solution, either containing paracetamol or a mixture of pharmaceuticals. The solution was kept in a plastic storage tank and continuously circulated through the plant using a centrifugal pump, maintaining a flow rate of 300 L h⁻¹ to ensure homogeneous mixing and efficient contact with all treatment units.

The operating temperature was controlled at 27 °C by means of two heat exchangers. The electrochemical system employed a filter-press reactor fitted with boron-doped diamond (BDD) electrodes (anode and cathode, 64 cm² each, Metakem™, Metakem GmbH, Usingen, Germany). Aeration was achieved through a cascade induced by the water flow, which guaranteed oxygen saturation and, consequently, the continuous electrogeneration of H₂O₂ at the BDD cathode. The electrode gap was fixed at 1.5 cm, and to enhance hydrodynamic conditions and favor mass transfer, a turbulence promoter was inserted into the cell.

For the solar irradiation stage, a compound parabolic collector (CPC) photoreactor was used, consisting of DURAN^® glass tubes,15 L total capacity (AO Sol, Carnaxide, Portugal). This configuration allowed an efficient concentration of solar light with a factor close to unity, owing to the arrangement of the parallel tubular modules. The tubes were mounted on aluminum supports over an inclined platform set at 20°, corresponding to the latitude of the experimental site in Mexico, to maximize solar radiation capture.

The solar photoelectro-Fenton (SPEF) assays were conducted during the summer of 2024, exclusively under sunny conditions. The intensity of natural UV-A radiation (300–400 nm) ranged between 30 and 35 W m⁻², as determined with a Kipp & Zonen CUV 5 radiometer (OTT HydroMet Corp., Sterling, VA, USA). The electrochemical cell was powered by a B.K. Precision 1688B DC supply, applying continuous current densities (j) of 20, 40, and 60 mA cm⁻². Each experimental run lasted 90 min, since longer treatment times were associated with a marked decrease in solar irradiance [25].

Before the trials, the BDD electrodes underwent a cleaning and activation protocol by applying j = 100 mA cm⁻² in a 0.05 M Na₂SO₄ solution for 120 min, ensuring optimal electrochemical performance throughout the experiments.

When O₃ alone (without passing current) and the combined SFEF/O₃ system were used, the O₃ gas was generated from dry air in an ozone generator provided by Ozone Carbar’s Inc. (Gto, México), with a maximum capacity of 7 L min⁻¹. O₃ was supplied to the solution through a glass diffuser, employing a Teflon connection from the ozone generator to the CPC-type photoreactor. The O₃ concentration in the solution was determined by the standard iodometric method (APHA, AWWA, and WPCF; 1995). These experiments were carried out at room temperature and in batch mode by continuously recirculating the solution and bubbling O₃ into it.

2.3. Analytical Measurements

2.3.1. High-Performance Liquid Chromatography (HPLC) Methodology

Chromatographic assays were performed on an Agilent 1260 Infinity HPLC (Agilent Technologies, Inc., Santa Clara, CA, USA) with a diode array UV detector and a Supelco C18 column (25 cm × 4.6 mm) with a 5 µm particle size (Merck KGaA, Darmstadt, Germany). All chemicals used were of pharmaceutical grade, and solvents were of HPLC grade. From a stock solution of paracetamol at 50 mg L⁻¹ in the mobile phase, working standard solutions were prepared by dilution in a range of 10–50 mg L⁻¹. A 10 µL aliquot of each solution was injected into the column, and the chromatograms were recorded at λ = 245 nm. Similar conditions were made to standardize the mixture of drugs and that of the intermediates catechol and phenol at λ = 245 nm.

Table 3. Conditions for Determinations by High-Performance Liquid Chromatography Methodology.

Column	Supelco C18 (25 cm × 4.6 mm), 5 μm
Wavelength	245 nm
Mobile phase	Water: Acetonitrile
Retention time	5.258 min
Flow rate	1 mL min−1
Temperature	25 °C
Injection volume	10 μL

shows the working conditions for the determination of paracetamol concentration in water. For this, the samples were injected after a simple pretreatment by solid phase extraction (SPE) with a Millex cartridge (Merck KGaA, Darmstadt, Germany) with a 0.45 µm Nylon membrane, a volume of 500 µL of solvent was eluted to activate the column, followed by 2 mL of the aliquots taken at different electrolysis times. Once the samples were obtained without salts, the filtered solutions were stored in vials at room temperature until their analysis. The amount of active ingredients was quantified by comparing the peak area with the concentration vs. absorbance regression previously obtained.

The decay of drug concentration under different electrolysis conditions was calculated from Equation (9) [26]:

$$\mathrm{\%}\mathrm{D}\mathrm{e}\mathrm{g}\mathrm{r}\mathrm{a}\mathrm{d}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}={\displaystyle \frac{∆c}{c_0}}100$$

(9)

where ∆c is the decay of drug concentration expressed (in mg L⁻¹) at the electrolysis time t (in min), and c₀ corresponds to the initial concentration.

2.3.2. Hydrogen Peroxide (H₂O₂) Electrogeneration/Accumulation

The concentration of accumulated H₂O₂ during the trials was determined by UV-Vis titration with titanium (IV) oxysulfate [Ti(SO₄)₂] at λ = 407 nm [27]. The Faradaic efficiency η in (%) of H₂O₂ accumulation is described by Equation (10):

$$\mathsf{\eta }={\displaystyle \frac{nF\left[{\mathrm{H}}_2{\mathrm{O}}_2\right]V_s}{It}}100$$

(10)

where n is the number of electrons required for O₂ reduction to H₂O₂ production. F is the Faraday constant (96, 500 C mol⁻¹), [H₂O₂] is the H₂O₂ concentration (in M), V_s is the solution volume (in L), I is the current intensity (in A), and t is the reaction time (in s).

2.3.3. Chemical Oxygen Demand (COD) Analysis

The estimation of the quantity of oxidizable material through chemical oxygen demand (COD) assays was followed by the 5220D method outlined in Standard Methods. The specific energy consumption per unit COD mass (EC_COD) at time t (in h) for each trial was calculated from Equation (11).

$${\mathrm{E}\mathrm{C}}_{\mathrm{C}\mathrm{O}\mathrm{D}}{\left(\mathrm{k}\mathrm{W}\mathrm{h}\right(\mathrm{g}\mathrm{C}\mathrm{O}\mathrm{D})}^{-1})={\displaystyle \frac{2.7\times {10}^{-7}{E}_{\mathrm{c}\mathrm{e}\mathrm{l}\mathrm{l}}It}{V_s∆\left(\mathrm{C}\mathrm{O}\mathrm{D}\right)}}$$

(11)

where E_cell is the average potential difference in the cell (in V), t is the electrolysis time (in h), and Δ(COD) is the decrease in COD at time t (in mg O₂ L⁻¹).

All the assays were performed in triplicate, reporting the average data with a 95% confidence interval in the figures of merit.

3. Results and Discussion

3.1. Solar Radiation

Figure 2 illustrates the variation in solar radiation intensity over time during the illumination of the CPC-type photoreactor. The experimental data were fitted to a polynomial regression model (R² = 0.9518) obtained during a representative SPEF track. The results show that the maximum solar irradiance occurred between 75 and 90 min of electrolysis, followed by a gradual decrease until reaching its minimum value at 240 min. This trend was consistent with the temperature evolution of the system, which increased from 24.5 to 29 °C, as recorded by the nearest Automatic Meteorological Station (EMAS) to the experimental site.

This observation highlights the potential to couple the photoreactor with photovoltaic cells in future applications, enabling estimation of the energy conversion efficiency of the system. Based on the irradiance profile, an operational time of 90 min was established as the standard electrolysis duration for each experimental day.

3.2. Electrogeneration of Hydrogen Peroxide at Solar CPC Photoreactor

Hydrogen peroxide (H₂O₂) is a highly versatile chemical agent, characterized by a relatively low oxidizing strength due to its standard reduction potential (E° = 1.763 V/SHE) [28]. The electrogeneration of H₂O₂ at the cathode in electrochemical systems is mainly influenced by factors such as the applied current density (j), the nature of the electrode material, and the operational mode of the process.

In this work, the objective was to assess the in-situ production of H₂O₂ at pilot scale, coupled with a CPC-type photoreactor, with the purpose of achieving high Faradaic efficiency and thereby minimizing the specific energy consumption, depending on both the electrode surface area and the SPEF operating conditions. For this purpose, a BDD/BDD electrode configuration (64 cm² geometric area each) was employed to treat a 30 L solution, continuously recirculated at 300 L h⁻¹. The supporting electrolyte consisted of 0.5 M Na₂SO₄, and the experiments were carried out under constant current densities of 20, 40, and 60 mA cm⁻² [29].

Figure 3a shows the evolution of H₂O₂ accumulation in the solution as a function of the applied current density (j). The increase in j enhanced the reduction in O₂ at the BDD cathode (Equation (2)), thereby promoting higher concentrations of electrogenerated H₂O₂. At j = 20 mA cm⁻² (●), the concentration reached 2.21 mM after 60 min of polarization, whereas at j = 40 mA cm⁻² (■), a slightly higher value of 2.43 mM was obtained. In contrast, the application of j = 60 mA cm⁻² (▲) favored an accumulation close to 3.0 mM.

The accumulation profile revealed a nearly linear increase during the first 30 min of electrolysis, followed by the onset of a plateau. This behavior can be attributed to the dynamic equilibrium between the continuous electrogeneration of H₂O₂ and its parallel loss processes. The main causes of H₂O₂ depletion are: (i) its anodic oxidation, yielding the weaker physisorbed hydroperoxyl radical (M(HO₂^•)) (Equation (12)), and (ii) its spontaneous chemical decomposition into H₂O and O₂ (Equation (13)) [30].

M + H₂O₂ → M(HO₂^•) + H⁺ + e⁻

(12)

H₂O₂ → H₂O + O₂

(13)

The evaluation of Faradaic efficiency (η) provides insight into the relationship between the amount of accumulated H₂O₂ and the corresponding electrical charge consumed during the electrochemical process. The η values were calculated according to Equation (10), under the assumption that n = 2, i.e., that the only cathodic reaction taking place is described by Equation (2).

As illustrated in Figure 3b, η decreased progressively with increasing current density (j), ranging from 52% to 27% at the initial stages of electrolysis for j = 20 mA cm⁻² (●), 40 mA cm⁻² (■), and 60 mA cm⁻² (▲). At longer electrolysis times, η exhibited a gradual decay for all conditions, mainly attributed to the enhancement of H₂O₂ decomposition pathways (Equations (12) and (13)) as its concentration increased in the medium.

Although higher current density was associated with lower Faradaic efficiency, the condition of j = 60 mA cm⁻² was selected for subsequent experiments, since it led to the highest H₂O₂ production, ensuring greater availability of oxidizing species for the SPEF process.

3.3. Degradation of Paracetamol with CPC-Type Photoreactor by SPEF Process

The experiments evaluated the degradation of 30 L solutions containing 20 mg L⁻¹ of paracetamol with 0.05 mM Na₂SO₄ and 0.5 mM Fe²⁺ at pH 3.0, 27 °C, and j = 60 mA cm⁻². Paracetamol was chosen as a model pollutant due to its global consumption, frequent detection in wastewater, and increased use during the COVID-19 pandemic; therefore, studying paracetamol under typical electrochemical oxidation conditions provides a reliable benchmark to assess process efficiency and applicability at pilot-plant scale.

As a preliminary test, direct photolysis of the solution without Fe²⁺ and current applied was carried out to evaluate the capacity of the action of sunlight to photolyze the drug. The paracetamol concentration was monitored by HPLC, as explained in Section 2.

Figure 4 demonstrates that direct photolysis alone was ineffective for the degradation of paracetamol, since after 90 min of irradiation, only about 10% of the initial concentration was removed (●). This confirms the strong photostability of paracetamol and the need for more advanced oxidation methods.

In contrast, the application of SPEF with 0.5 mM Fe²⁺ (■) led to the complete degradation of the drug within approximately 50 min, underscoring the high efficiency of electrogenerated hydroxyl radicals, particularly when their production is enhanced by natural solar irradiation. The process relies on the synergistic action between electrochemically generated H₂O₂, the catalytic role of Fe²⁺ ions, and the additional contribution of solar photons.

Figure 5 illustrates the chromatographic evolution of paracetamol during its oxidation by the SPEF process. At the onset of treatment, the compound exhibited a well-defined chromatographic peak with a retention time of 2.25 min. As the reaction progressed, this peak progressively decreased in intensity, reflecting the continuous degradation of the pharmaceutical. After approximately 80 min of electrolysis, the paracetamol signal had virtually disappeared, in full agreement with the degradation profile reported in Figure 4 (■).

These results provide further confirmation of the high efficiency of the SPEF process at pilot scale, demonstrating its ability to achieve the complete elimination of paracetamol from aqueous matrices under the tested conditions.

3.4. Identification of Intermediates

It is known that paracetamol undergoes oxidation processes, giving rise to intermediate compounds mainly polyphenols, including catechol, aminophenol, and resorcinol, among others [31,32,33]. In the SPEF process, the HPLC analysis confirmed the formation of aromatic intermediates from the first 10 min of electrolysis. Two main intermediates were detected: catechol (■), which reached 3.25 mg L⁻¹ at 10 min and disappeared by 60 min, and phenol (●), which peaked at 2.40 mg L⁻¹ at 30 min before being completely degraded by the end of the process, as can be seen in Figure 5. This trend can be observed in their concentration vs. electrolysis time plots shown in Figure 6. It is important to highlight that paracetamol, as well as its transformation aromatic by-products, can be successfully degraded after a total reaction time of 80 min, as similarly found for other drugs [34].

3.5. Cyclic Voltammetric Analysis

Figure 7 presents the cyclic voltammograms obtained for a 20 mg L⁻¹ paracetamol solution, recorded at a scan rate of 100 mV s⁻¹ in 0.1 M phosphate buffer (pH = 7.0) using an Epsilon™ potentiostat/galvanostat (Bioanalytical Systems, Inc., West Lafayette, IN, USA). In the absence of paracetamol, the supporting electrolyte exhibited no electroactive signals (▬), confirming that the phosphate medium itself did not contribute to any detectable redox activity. When the system contained 0.5 mM Fe²⁺, a well-defined oxidation peak at 0.42 V and a corresponding reduction band at 0.30 V were observed, which can be attributed to the Fe³⁺/Fe²⁺ redox couple (▬). In contrast, after 90 min of treatment with the SPEF process (▬), the voltammogram displayed a single irreversible oxidation peak centered at 0.44 V. This response is ascribed to the formation of intermediate species that are difficult to detect by HPLC, or to short-chain carboxylic acids complexed with Fe³⁺, which retain electroactive properties identifiable by cyclic voltammetry [35,36].

These results suggest that the degradation of paracetamol under SPEF proceeds through the generation of electroactive by-products that are poorly oxidizable and persist in the solution, thereby explaining the partial mineralization observed at the end of the process.

3.6. COD Removal, ACE Evaluation, and Energy Consumption

To better understand the oxidative capacity of the tested SPEF process, the corresponding solution COD was determined, and the percentage of COD removal was calculated from Equation (14):

$$\mathrm{\%}\mathrm{C}\mathrm{O}\mathrm{D}\mathrm{r}\mathrm{e}\mathrm{m}\mathrm{o}\mathrm{v}\mathrm{a}\mathrm{l}={\displaystyle \frac{∆\left(\mathrm{C}\mathrm{O}\mathrm{D}\right)}{{\mathrm{C}\mathrm{O}\mathrm{D}}_0}}100$$

(14)

where COD₀ is the initial COD value of the solution (in mg O₂ L⁻¹). The average current efficiency (ACE in %) was then estimated according to Equation (15) [37]:

$$\mathrm{\%}\mathrm{A}\mathrm{C}\mathrm{E}={\displaystyle \frac{{FV}_s∆\left(\mathrm{C}\mathrm{O}\mathrm{D}\right)}{8It}}100$$

(15)

where Δ(COD) is expressed in mg O₂ L⁻¹, 8 is the oxygen equivalent mass (in g eq⁻¹), and t is the electrolysis time (in s).

Figure 8A shows that 78% of COD was removed after 90 min of the SPEF process (●), indicating that highly persistent by-products remained in the final treated solution, in agreement with the cyclic voltammetric analysis. Regarding the ACE value (■), the initial value of 15% was progressively slowed down to 8% at 90 min. This decay can be related to two simultaneous effects, the gradual removal of organic load and the production of more hardly oxidizable by-products [38]. The rapid loss of ACE yielded a continuous enhancement of EC_COD calculated by Equation (11) with electrolysis time, as shown in Figure 8B. As can be seen, at 90 min, a low EC_COD of 0.0519 kWh (g COD)⁻¹ was obtained, a similar value to that reported by Zhang et al. [39] for tetracycline removal by PEF without considering the energy cost of the UV lamp.

3.7. Treatment of a Mixture of Drugs with the Coupled SPEF/Ozone Process

Having established that the SPEF process achieves high degradation efficiencies for paracetamol, the subsequent experiments focused on a multi-component system representative of pharmaceutical mixtures used during the COVID-19 pandemic for symptomatic treatment within the Mexican health system. The selected drugs included dexamethasone, paracetamol, amoxicillin, and azithromycin. Recent studies have reported the persistence and accumulation of these pharmaceuticals in aquatic environments, raising growing environmental concerns. Therefore, exploring effective strategies for their removal is of significant relevance, and this work proposes SPEF as a viable alternative for their degradation [38].

To seek not only the treatment of water contaminated with drugs but also its disinfection, it was decided to carry out tests using ozone. Figure 9 (■) shows the time course of the overall concentration of a mixture of dexamethasone (0.25 mg L⁻¹), paracetamol (50 mg L⁻¹), amoxicillin (50 mg L⁻¹), and azithromycin (16 mg L⁻¹) with 0.05 M Na₂SO₄ at pH = 3.0 by applying 5 L min⁻¹ of O₃ flow. The action of this oxidant, combined with sunlight, yielded 34% content removal at 180 min of electrolysis. This decay is higher than 60% for the SPEF/O₃ process (●), indicating the beneficial effect of the generated ^•OH oxidants on the process. Since paracetamol was removed in less than 90 min (see Figure 4), the other pharmaceuticals tested were much more recalcitrant to oxidation. Regarding the COD decay between 0 and 180 min of electrolysis, 41% was abated, pointing to the remaining part of the drugs and their degradation by-products.

It is important to emphasize that the addition of ozone can enhance the degradation of recalcitrant pharmaceuticals, particularly those with an aromatic structure. However, this process may also lead to the formation of aromatic intermediates, which could persist in solution due to their limited susceptibility to attack by the generated reactive oxygen species (ROS). In parallel, the electrocatalytic activity of the electrodes may decrease over the course of electrolysis, potentially as a result of catalyst deactivation by iron poisoning and/or the accumulation of oxidation intermediates formed in situ [40,41,42,43,44,45,46].

Based on the results of this research, it is highlighted that the main novelty of this work is the demonstration of the synergistic use of a solar photoelectro-Fenton system coupled with ozone in a pilot-scale CPC reactor for the efficient degradation of complex mixtures of drugs related to the treatment of COVID-19, which represents a significant advance towards the real implementation of hybrid EAOP technologies for the treatment of water contaminated with pharmaceutical residues.

Further information on kinetic behavior is presented in Tables S1 and S2.

4. Conclusions

The COVID-19 pandemic generated profound consequences worldwide, not only from a public health perspective but also in terms of environmental impact. During the health crisis, medical services relied on the pharmaceutical resources available at that time, including various symptomatic treatments. As a result, numerous therapeutic protocols were implemented in the absence of specific antiviral drugs. However, one of the unintended outcomes has been the emergence of water pollution, since elevated concentrations of these pharmaceuticals have been detected in wastewater effluents across different regions of the world. This occurs because a significant fraction of the administered drugs is not metabolized in the human body and is instead excreted, mainly through urine and sweat. Consequently, the proper treatment of these contaminated water streams represents a pressing challenge for the future.

In this study, the degradation of paracetamol (50 mg L⁻¹) as well as a drug mixture representative of COVID-19 symptomatic treatments—namely dexamethasone (0.25 mg L⁻¹), paracetamol (50 mg L⁻¹), amoxicillin (50 mg L⁻¹), and azithromycin (16 mg L⁻¹)—was evaluated using solar photoelectro-Fenton (SPEF) and SPEF combined with ozonation (SPEF/O₃) processes. All experiments were conducted in a pilot plant equipped with a CPC-type photoreactor (30 L working volume) coupled to a filter-press electrochemical cell with a BDD/BDD electrode configuration.

For the SPEF process, complete degradation (100%) of paracetamol was achieved under j = 60 mA cm⁻², with a COD removal of 78%, a Faradaic efficiency of η = 8%, and an energy consumption (ECCOD) of 0.0518 kWh (g COD)⁻¹. In the case of the drug mixture, the SPEF/O₃ system significantly outperformed the standalone O₃/solar process, achieving nearly 60% degradation and 41% COD abatement.

The findings of this research provide a promising perspective toward addressing a real and current environmental challenge. The results demonstrate that electrochemical advanced oxidation processes (EAOPs) coupled with solar irradiation are highly effective for the degradation of complex mixtures of recalcitrant pharmaceuticals, highlighting their potential applicability for large-scale water treatment.

Therefore, the main contribution of this study is to demonstrate experimentally, systematically, and with analytical support that a solar-powered hybrid SPEF/O₃ system is highly effective in the degradation of pharmaceuticals widely used during the COVID-19 pandemic. This innovation focuses not only on technical efficiency but also on its environmental, economic, and social potential, aligning with the principles of sustainability and public health.

This work represents a solid step toward cleaner, more scalable, and more relevant environmental remediation technologies to address the emerging threats of pharmaceutical contamination in wastewater. The use of enriched raw water constitutes an intermediate approach to a real-world system, as it allows for the evaluation of process efficiency under controlled conditions; however, this strategy still has limitations due to the complexity of real-world matrices. Therefore, further research is needed to validate the technology directly in real-world wastewater to confirm its performance, robustness, and applicability in practical treatment scenarios.