Optimization of Photo-fentom like process for the remediation of sodium diclofenac residues in water samples

Worldwide, there is an increasing incidence of contaminants in aqueous matrices, among them, antibiotics, pesticides and pharmaceutical products. This problem, coupled with the occurrence of these pollutants at trace levels, creates unique challenges for the analytical detection and performance evaluation of the removal of these contaminants from water. The purpose of this experiment was to optimize the operational conditions of the Photo-fentom like process of sodium diclofenac residues by Response Surface Methodology (RSM), based on analysis in aqueous solution. The drug was determined via UV-Vis spectrophotometry using a 2 3 factorial design with a central point to evaluate the degradation of the sodium diclofenac. The design was composed of two levels and three factors: (X 1 ) Irradiation time, ranging from 2 to 4 h; (X 2 ) Hydrogen peroxide content, ranging from 1 to 7%; and (X 3 ) Fe 2+ concentration, ranging from 25 to 100 mg L -1 . According to the levels defined for each parameter, the optimized methodology showed that the best degradation of the drug was achieved by combining 2 h of irradiation, 1% Hydrogen peroxide solution and 25 mg L -1 of solution containing Fe 2+ , where 97.04% of drug degradation was achieved. From ANOVA it could be inferred that the concentration of Fe 2+ (p = 0.13044) and the interaction irradiation time with Fe 2+ concentration (X 1 X 3 ) (p = 0.0439) had the highest significance in the degradation process. The experimental planning was useful to indicate the region of maximum degradation, therefore, the methodology was suitable for degradation of residues of this drug in water samples.

from 25 to 100 mg L -1 . According to the levels defined for each parameter, the optimized methodology showed that the best degradation of the drug was achieved by combining 2 h of irradiation, 1% Hydrogen peroxide solution and 25 mg L -1 of solution containing Fe 2+ , where 97.04% of drug degradation was achieved. From ANOVA it could be inferred that the concentration of Fe 2+ (p = 0.13044) and the interaction irradiation time with Fe 2+ concentration (X1X3) (p = 0.0439) had the highest significance in the degradation process. The experimental planning was useful to indicate the region of maximum degradation, therefore, the methodology was suitable for degradation of residues of this drug in water samples. Keywords: Advanced oxidative process; Diclofenac sodium; Environmental contamination; Spectrophotometry; Water.

Introduction
Diclofenac sodium (DCF) is another one of several anti-inflammatory drugs used to treat inflammatory diseases, and various types of pain (Tiwari, 2015). The annual consumption of DCF has reached over 60 tons in many countries (Lonappan et al, 2016). However, DCF waste is poorly treated and reaches water treatment plants, resulting in the residue of DCF in surface and groundwater. In addition, DCF at low concentration can cause cytological changes in animals in aquatic environment (Li et al, 2021, Acuña et al., 2015, which can cause a risk to aquatic ecosystems. Thus, DCF exposed to the natural environment needs to be removed urgently. Sodium diclofenac is available on the drugstores as a free salt, sodium salt, or potassium salt. The latter salt is more soluble, promoting a higher rate of absorption and thus a faster analgesic effect compared to the other orally administered forms. Sodium diclofenac sodium, a non-steroidal drug, acts in the body by decreasing the production of prostaglandins, which play an important role in causing inflammation, pain, and fever. The unbridled consumption of this drug linked to a wide diversity of applications, which does not restrict its purchase in drugstores, consequently contributes to the contamination of effluents when it comes to the issue of disposal and waste production (Li et al., 2021;Lima et al., 2015;Santos & Bergold, 2007).
The pharmaceutical industry is established as one of the most prominent industrial sectors, which works with the conservation of human health over time, promoting an increase in both quality and life expectancy of the world population.
Every year, large quantities of pharmaceutical products are produced with application in the most diverse areas of human and animal health, and most of the active ingredients used are biologically active organic compounds. The pharmaceutical sector presents a definition as the branch of economy that incorporates the set of activities involved in the production, commercialization and transportation of pharmochemicals, drugs and pharmaceutical preparations (Vieira & Santos, 2020;Alygizakis et al., 2016).
The use of chemical treatments as an alternative technological resource for the treatment of industrial effluents has attracted considerable attention, showing advantageous characteristics such as ease of automation and a reduction in physical space, among which are included the oxidative and photo-oxidative processes, in the set called Advanced Oxidative Processes (AOP). The AOP are processes based on the generation of free radicals, mainly the hydroxyl radical (HO-), and present high efficiency in the removal of non-biodegradable pollutants or of high persistence, for which, the conventional effluent treatments (sedimentation, coagulation/flocculation, biological filters, among others) are not effective. These processes are characterized by facilitating the transformation of various organic contaminants into less complex chemical species (inorganic anions, water or carbon dioxide) (Araújo et al., 2016;Sun et al., 2016;Tong et al., 2019;Carra et al., 2015;Cihanoglu, Gunduz & Dukkanci, 2015). The reduction in the use of chemicals is a great benefit, since the electron is the main reactant in the process, and the estimate of reuse of the coproducts generated, shows an excellent initiative within the current global scenario of sustainability. These technologies submerge reactive oxygen species (ROS), which makes possible the degradation of organic pollutants with various chemical structures and functional groups to fewer toxic substances. The correct management, recycling and treatment of these wastes should be performed, in order to ensure that the emission of substances of high concern and contamination is avoided, ensuring environmental protection of human health (Hahladakis et al., 2018;Li et al., 2021;Hu, Zhai and Zhu, 2021).
The Fenton process can be understood as a system involving a set of cyclic reactions in an acidic medium, where the hydroxyl radical (an oxidizing agent used in the degradation of organic material) can be generated as a product of hydrogen peroxide decomposition in the presence of Fe 2+ or Fe 3+ ions (Aydin et al., 2018;Baloyi, Ntho & Moma, 2018;Ameta et al., 2018). In the photo-Fenton process, radiation is used to increase the speed of oxidation reactions in the sample. The incidence of radiation promotes electron transfer from the ligands of the hydroxylated Fe 2+ and Fe 3+ species to the metal, providing, the formation of the hydroxyl radical and the regeneration of the Fe ion (Faust & Hoigné, 1990;Ammar et al., 2016;Bel Hadjltaief et al., 2014).
In view of the above, this research aims to study to optimize the application of the photo-Fenton process in the treatment of solution containing the active ingredient sodium diclofenac.

Instruments
UV analysis was performed by an UV spectrophotometer Spectroquant Prove 600 (Merck, Darmstadt, Germany).

UV analysis
For the UV analysis, the samples filtered after the degradation assays were used. All tests were performed in triplicate, at a wavelength of 330 nm, in order to verify the decrease in the concentration of the analyte before and after the oxidative process.

Experimental Design
To evaluate the efficiency of the degradation process of the drug, a 2 3 factorial design with central point was (1)

Photodegradation experiments
To perform each experiment, initially, the beaker was washed with distilled water. First, adequate volumes of H2O2 and FeSO4.7H2O (according to the experimental design) and diclofenac sodium solution were mixed in a 600 mL beaker to obtain 200 mL of a 10 mg mL -1 solution of the drug, as well as in the experiments performed by Davididou et al., (2017);Carra et al., (2015). Photodegradation experiments were conducted with a black light fluorescent lamp FoxLux® with irradiation power of 27 W and frequency of 60 Hz. After the predefined irradiation times, the sample was filtered and analyzed in a spectrophotometer to evaluate the degradation of the analyte.

Factorial Design Performed
Initially, the effect of Fe 2+ concentration, irradiation time and H2O2 content on the degradation capacity of the photo-Fenton system was investigated by a factorial planning system of experiments, using sodium diclofenac solution. In these studies (results shown in Table 1) a strong combined effect between both variables was verified, as well as a maximized degradation efficiency under experimental conditions represented by: irradiation time: 2 h; Fe 2+ : 25 mg L -1 ; H2O2: 1 %. Under these conditions, the minimum Fe 2+ concentration (25 mg L -1 ) was sufficient for maximum hydroxyl radical (-OH) production from the H2O2 content (1%).

Estimated Model
The adjustment of the statistical model of factorial planning is verified by the coefficient of determination (R 2 ). From the data in Table 3, the coefficient found was: R 2 = 0.9992 (R 2 adj = 0.9987) indicating that the model was adequate. From the ANOVA (Table 2) the F and p values are presented, showing the significance of the factors in the degradation process studied. P values are used to confirm the significance of each coefficient, i.e., the lowest p value is at the highest effect (Zhao et al., 2011). According to the F and p values (Table 3), the factor with the largest effect is on Fe 2+ concentration (X3, p= 9.88.10 -8 ); however, this analysis indicates that only the irradiation time x Fe 2+ concentration interaction (X1X3) was significant (p = 0.0439).

Response surface plot analysis
Response surface plots are very useful to visualize the effects of two factors on the response, as well as the identification of the optimal values, for obtaining the maximum response (Silva, Azevedo and Rezende, 2016).
Response Surface Methodology (RSM) is a statistical method that uses quantitative data from a factorial planning to determine multivariate equations. Unlike conventional empirical methods, RSM generates a mathematical model, taking into account the possible interrelationships between the test variables, minimizing the number of experiments (Song et al., 2011).
The effects of the independent variables (factors) and their interactions on the response can be observed in three dimensions by means of response surface analysis . Figures 1, 2 and 3 show the main interactions of the process: Fe 2+ concentration x irradiation time; H2O2 content x irradiation time and H2O2 content x Fe 2+ concentration. The graphs were plotted using the z-axis (sodium diclofenac concentration in mg mL -1 ) against two independent variables.     Source: Research data. Figure 3 shows the interaction between H2O2 content and Fe 2+ concentration in the degradation of diclofenac sodium.
Evaluating the y-axis (Fe 2+ ) in relation to the z-axis (DCF) it is possible to observe the decrease in the concentration of the analyte, by the extremity of the response surface pointing to the 20 mg L -1 Fe 2+ concentration. According to Martins et al. (2011), it is important to determine the ratio between the reactants [H2O2]:[Fe 2+ ], as a way to minimize the sequestering effects of hydroxyl radicals, caused in some cases by excess H2O2. In our study, it can be inferred that the lower concentration of Fe 2+ in solution was able to saturate all the H2O2 in the process, which possibly promoted the best yield regarding the degradation of the drug.

Conclusion
Current studies have shown the need to develop treatments facing the problems arising due to the widespread of emergent contaminants. In this investigation, an optimized methodology for degradation of diclofenac sodium, based on UV-Vis spectrophotometric analysis, was performed, reducing the initial concentration of the drug by approximately 97%. The degradation of diclofenac in the eight experiments was enhanced by the combination of lower peroxide and Fe 2+ contents.
For future researches, it would be interesting to evaluate the degradation of commercial samples of the drug and to test other types of lamps and/or radiation.