DEGRADATION OF DICLOFENAC SODIUM BY USING ADVANCED

OXIDATION PROCESSES

By

WAQAS AHMAD

(Regd. No. 2013-CHE-081)

Synopsis submitted for the degree of M.Phil

In
Chemistry

Session 2016-2018

Department of Chemistry
Faculty of Basic and Applied Sciences
The University of Poonch Rawalakot
Azad Jammu and Kashmir

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 THE UNIVERSITY OF POONCH RAWALAKOT
FACULTY OF BASIC AND APPLIED SCIENCES

Synopsis for M.Phil Degree in Chemistry

Title: Degradation of Diclofenac Sodium by using Advanced Oxidation Processes

Name of student: Waqas Ahmad

Registration number: 2013-CHE-081

Date of admission: 1st December, 2016

Date of initiation: 6th March, 2017

Probable duration: Four semesters

SUPERVISORY COMMITTEE

i. Supervisor Dr. Faiza Rehman ------------------

Assistant Professor in Chemistry

ii. Co-Supervisor Dr. Murtaza Sayed -----------------

Assistant Professor in NCEPC, UOP

iii. Member Dr. Shabnam Shahida -----------------

Assistant Professor in Chemistry

iv. Member Dr. Qamar Din

-----------------Assistant Professor in Mathematics

Incharge
Department of Chemistry

Dean Director
Faculty of Basic and Applied Sciences Advanced Studies and Semester
Affairs

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 ASTRACT

Diclofenac sodium is one of the most popular anti-inflammatory drug used

for arthritis, osteoarthritis and skeletal muscular injuries. Literature show that high

concentration of this drug is present in water. Several adverse effects of diclofenac

sodium on living beings have been reported. Hence it should be removed from

environment. The effect of different advanced oxidation processes towards the

degradation of diclofenac sodium will be investigated. The rate of mineralization

and kinetics will be conducted. The effect of radical promoters and inhibitors on

the degradation of diclofenac sodium will be investigated.

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 INTRODUCTION

Pharmaceutical are medicinal compounds for human and veterinary life and

have been used everywhere in the world (Klavarioti et al., 2009). Pharmaceutical

compounds are being used for different purposes in society but these compounds

release very toxic contaminants in environment (Ptneedi and Prasadue, 2015). The

remains of pharmaceuticals are present in sewage and their removal from waste

water by conventional methods is difficult (Giri et al., 2010). Pharmaceutical is a

group which include drug components of cosmetics, food supplements, metabolites

and intermediate products (Esplugas et al., 2007).

Industrialization, urbanization, deforestation and pollution adversely effects

aquatic life. Trace concentration of numerous organic and endocrine disrupting

compounds like precipitating drugs are reported to cause water pollution. Increase

in level of naturally occurring organic materials seeps down into the lakes, rivers

and streams (Caliman and Gavrilescu, 2009; Onessios et al., 2009; Li et al., 2010).

From above discussion it can be concluded that hazardous pollutants must be

removed from water for protection of aquatic and human life. Our focus among

these pollutant is on diclofenac sodium which is a pharmaceutical drug. Diclofenac

sodium (C14H10Cl2NO2Na) is commonly used as anti-inflammatory drug. It is

present in two important salt forms diclofenac sodium and diclofenac potassium.

The structural form of diclofenac sodium is given in Figure 1.

Cl O
NH
Na

Cl

Figure 1. Sodium (2[(2, 6-diclorophenyl) amino] phenyl acetate)

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 Diclofenac sodium (2[(2, 6-diclorophenyl) amino] phenyl acetate) is anti-

inflammatory drug used for the treatment of arthritis, osteoarthritis and skeletal

muscular injuries in human and veterinary medicine (Gazdova et al., 2015). It is

used in the form of tablets, capsule, intravenous solution and in dermal ointments

(Buser et al., 1998). It reduces pain and inflammation in patients. Diclofenac

sodium is mostly used as a pain killer and waste water treatment plants do not

completely remove it from waste water (Fischer et al., 2015). Diclofenac sodium is

excreted 15 percent unchanged after consumption. Literature show it is one of the

most discovered pharmaceutical in water and urban waste water (Rizzo et al.,

2009). Although the toxic effects of diclofenac is relatively low but when

diclofenac is combined with other pharmaceuticals, its toxicity increased (Lionidas

et al., 2005).

There are many conventional methods for removal of pharmaceuticals

including flocculation, filtration, adsorption and oxidation of waste water. Bank

filtration is a conventional method for river water treatment (Zwienerm and

Frimmel, 2000). Partial oxidation of organic contaminants result in formation of

more toxic intermediates than parent compounds. Partial oxidation methods cannot

remove toxic compounds completely from water (Rizzo et al., 2011). Applications

of various bioassays to characterize the effluent quality from different advanced

oxidation processes (AOPs) could be useful tool to optimize the performance of

AOPs.

AOPs are efficient method for removal of organic contaminants from waste

water. AOPs can be applied for disinfection of water, air and soil. AOPs are

successful methods for converting pharmaceutical drugs, pesticides and endocrine

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disruptors into biodegradable substances. AOPs involve high operating costs due to

input of chemicals and energy required (Cominelis et al., 2008).

AOPs produce less toxic organic and inorganic substances as a result of

mineralization. In this process water contaminants are converted into more

biodegradable substances (Covinich et al., 2014). AOPs emit reactive oxidizing

agents like hydroxyl radical (•OH). This radical initiate oxidative degradation of

organic compounds and mineralize them into CO2, H2O and less harmful inorganic

ions (Karale et al., 2013).

C14H10Cl2NO2Na + 3H2O2 + 15O2 → 14CO2 + 7H2O + NaCl + HCl+ HNO3

AOPs use strong oxidizing agents like hydrogen peroxide (H 2O2), ozone

(O3) and catalysts in combination with irradiation or separately. Among these

methods most effective were those which were initiated by irradiation for waste

water treatment. AOPs involved production of highly reactive hydroxyl radicals,

which are consider as strong oxidizing agents in aqueous system (Staehelin and

Hoigne, 1985). In mineralization process organic compounds are converted into

water, carbon dioxide (CO2) and mineral salts by using hydroxyl radicals (Chen et

al., 2000). The important AOPs which utilize UV are UV/H2O2, UV/O3, UV/TiO2

and UV/Fenton. In dark oxidation process no UV source is used. These include

ozonation, Fenton’s reagent, ultrasound and microwaves. Among these methods,

ozonation, UV/H2O2 and photo catalysis utilizing UV or solar irradiation with TiO 2

are most effective method.

From the above discussion it can be summarized that diclofenac present in

aquatic environment is of great environmental problem. In literature various

advanced oxidation techniques such as ozonation, electrochemical, electro Fenton,

Fenton, photo Fenton and sonolysis have been frequently applied for the removal

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of diclofenac from aqueous media. In our present research work, the removal of

diclofenac sodium from waste water will be carried out through UV - C 254 nm

wavelength lamp, which is a promising tool for the removal of organic pollutant

from waste water. The UV - C 254 nm wavelength lamp produce oxidizing and

reducing radicals (•H, •OH, e-aq), which can attack the organic pollutant. These

species cause their destruction through oxidation and reduction processes into

water, CO2 and mineral acids. The main aim of our research work is to find out a

sophisticated method for the complete degradation of pharmaceutical diclofenac

sodium in waste and drinking water, which are summarized below:

 To find out the effect of UV - C 254 nm wavelength lamp on the

degradation of diclofenac sodium in waste and daily use water.

 To investigate the removal efficiency of diclofenac sodium by UV - C 254

nm wavelength lamp up to complete mineralization.

 To study the effect of optimized dose of UV - C 254 nm wavelength lamp

for the degradation of different concentrations of diclofenac sodium in

water.

 To find out the effect of UV - C 254 nm wavelength on the degradation of

diclofenac sodium in the presence of radical promoters and inhibitors,

found in water.

 To find out the mechanism and kinetics of diclofenac sodium degradation.

 To investigate the computer base kinetic modeling by using known rate

constant for the diclofenac sodium degradation by using UV - C 254 nm

wavelength lamp.

 Kinetic modeling will be compared with experimental data.

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 REVIEW OF LITERATURE

Vogna et al. (2003) reported that diclofenac exhibits adverse effects on fish.

He studied the kinetics of degradation reaction by using AOPs. Ozonation and

UV/H2O2 proved to be effective in diclofenac degradation, ensuring complete

conversion of chlorine into chloride ions. Degree of mineralization of 32 percent

for ozonation and 39 percent for UV/H2O2 processes after 90 minutes treatment. It

was observed that kinetic constant value of (1.74 × 1 04 - 1.84 × 104 M-1S-1) were

estimated for diclofenac ozonation in the pH range of 5 to 6.

Hofmann et al. (2006) explained the degradation kinetics of diclofenac and

formation of different by products by using heterogeneous catalysis. Different

pathways like hydroxylation, dehalogenation and cleavage of NH-bridge were

proposed for degradation of intermediate products. The results showed that high

degradation rate can be achieved at 20 for full metal catalysts and mixed metal

oxide catalysts.

Hartmann et al. (2007) reported the sonolysis of diclofenac in water at

ultrasound frequencies of 24 kHz, 216 kHz, 617 kHz and 850 kHz. Various

catalysts like TiO2, SiO2, SnO2 and titanosilicate were used in the study.

Degradation of diclofenac at 617 kHz followed first order kinetics. TiO 2 increased

the rate of degradation of diclofenac. The concentration of diclofenac decreased

from 100 percent to 16 percent within 30 minute of irradiation. As a result of

sonolysis process chlorinated phenols and carboxylic acid derivatives were

produced. These by products were detected by HPLC - MS and GC - MS

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 Coelho (2009) used ozonation process for degradation of diclofenac. The

results showed that ozone removed more than 99 percent of diclofenac having

initial concentration of 0.68 mmol/L after 30 minutes treatment of absorbed ozone

dose of 0.22 g/L. Different tests like acute toxicity, biodegradability and respiration

inhibition in activated sludge showed that ozonation increased diclofenac

degradation.

Rizzo et al. (2009) study the degradation and mineralization of diclofenac

in batch reactor system by UV absorbance and chemical oxygen demand

measurements for initial concentration of (5 - 80 mgL -1) and photocatalyst

concentration of (0.2 to 1.6 g TiO 2 L-1). Bioassays (Daphnia magna, Pseudo-

kirchneriella subcaoitata and Artemia Salina) were performed to measure the

detoxification potential of diclofenac. Degradation process follow first order

kinetics, at concentration of (40 - 80 mgL-1). Results showed that at 1.6 gL-1

concentration TiO2 photocatalyst degradation rate follow second order kinetics.

Toxicity of diclofenac samples on different bioassays varied due to formation of

intermediate products. UV absorbance analysis was found to be useful for the study

of degradation rate of organic intermediates.

Naddeo et al. (2009) reported that diclofenac show adverse effects on

aquatic life. They employed different AOPs like ozonation and sonolysis for

removal of diclofenac from water metrics. Ozonation caused degradation of

diclofenac to 22 percent and for sonolysis it was 36 percent after 40 minutes of

treatment. It was observed that combined effect of ozonation and sonolysis lead to

higher mineralization about 40 percent for 40 minutes treatment.

Madhavan et al. (2010) reported that diclofenac act as pollutant in aqueous

system. Degradation study of diclofenac was explained by sonolytic, photocatalytic

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and sonophotocatalytic methods by using three catalysts (TiO 2, ZnO and Fe-ZnO).

Rate of degradation of diclofenac was of first order kinetics. It was observed that

sonophotocatalytic method using TiO2 under UV-Visible radiation enhanced

degradation process but it lowered the mineralization process. Fe - ZnO increased

degradation and mineralization processes.

Rivas et al. (2010) deduced the kinetics for degradation of diclofenac by

estimating the quantum yield. Initial concentration of diclofenac showed maximum

degradation. The rate of degradation increases in the presence of oxygen. The

mineralization also increased from 30 percent to 80 percent in the presence of

oxygen instead of air. The presence of free radicals promoters did not enhance the

removal efficiency of diclofenac.

Deng et al. (2013) prepared a magnetic nanoscaled cobalt ferrite (CoFe2O4)

catalyst and used it for activation of ozone to generate sulphate radicals for

degradation of diclofenac. Catalyst was characterized by using different techniques

like electron microscopy, X-ray diffractometry, Fourier transform infrared

spectroscopy and vibrating sample magnetometer. It was demonstrated that

CoFe2O4-300 exhibited complete removal of diclofenac in 15 minutes. By

decreasing pH range from 5 to 9 degradation of diclofenac increase. Morever,

increase in concentration of catalyst and oxone both had positive effect on

degradation of diclofenac.

Yu et al. (2013) reported the absolute rate constants for reaction of

diclofenac sodium and model compound (2, 6-dicloraniline) with two major

advanced oxidation/reduction processes (AO/RP). The radicals used in the study

were hydroxyl radical (•OH) and hydrated electron (e-aq). The bimolecular rate

constant (M-1s-1) for •OH was (9.29 ± 0.11) × 109. In addition, degradation

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mechanism and major by products were elucidated using Co60 ɣ-irradiation and LC

- MS.

Baea et al. (2013) demonstrated the degradation of diclofenac by using

Fenton process with pyrite catalyst. The pH of solution was (5.7 to 4.1) with

addition of pyrite (0.5 to 4.0 mM) and Fe (II) concentration increased from (0.07 to

0.52 Mm). Classic Fenton system showed only 65 percent removal of diclofenac in

180 sec but pyrite Fenton system showed 100 percent removal of diclofenac in 120

sec. The study also concluded that •OH radical enhanced degradation rate.

Intermediates were also degraded in 120 second and diclofenac converted into

organic acids, HCl and CO 2. The results showed that by increasing pyrite and H 2O2

concentration degradation of diclofenac increased.

Czech et al. (2013) observed the photocatalytic oxidation of diclofenac,

metoprolol, estrone and chloramphenicol in reactor tube by using TiO 2.

Photocatalysts were characterized by BET, XRD and SEM. It was observed that

anatase TiO2 had highest photocatalytic oxidation activity for diclofenac,

chloramphenicol and estrone. The photo-oxidation of all pollutants showed first

order kinetics with values ranging nearly 0.46 × 10 -2 min-1 and for estrone removal

over Tytanpol was 1.87 × 10-2 min-1. The highest initial reaction rates for

metoprolol were 1.9 × 10-6 mol dm3 min-1.

Ji et al. (2017) carried out electrooxidation method for degradation of

diclofenac with boron-doped diamond (BDD) and Ta/PbO2 anodes. Different

parameters like applied current density, pH value, initial concentration and

temperature were investigated. It was concluded that Ta/PbO2 anode greatly

oxidized diclofenac.

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 MATERIALS AND METHODS

SELECTION OF EXPERIMENTAL MATERIAL

Diclofenac sodium which is target pollutant in this research will be taken

from Fisher Scientific. The oxidants hydrogen peroxide (H2O2), Sodium

persulphate (PS) and sodium peroxy monosulphate (PMS) used as oxidants will be

purchased from Sigma Aldrich. Reactions will be carried with different oxidant

concentration in order to investigate degradation by AOPs.

PREPARATION OF SOLUTIONS

Solutions of different concentrations of diclofenac sodium will be prepared

by using triply distilled Milli-Q water purification system (Resistivity ≥ 18.2

MΩ.cm). Solutions of different concentrations of hydrogen peroxide (H 2O2),

Sodium persulphate (PS) and sodium peroxy monosulphate (PMS) will be

prepared. Different concentration of catalysts will be prepared for degradation

study.

SPECTROPHOTOMETRIC STUDIES

UV visible spectrophotometer and high performance liquid chromatograph

with mass spectrometry (HPLC - MS) will be used to study the degradation of the

compound. Calibration plot for diclofenac sodium will be carried out. UV - C 254

nm wavelength lamp will be used for the irradiation of samples. Calibration of UV

- C 254 nm wavelength lamp will be used by applying iodometry solution.

EFFECT OF pH

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 The pH meter (Benchtop pH/v meter) will be employed for accurate pH

measurement of sample solutions before and after irradiation.

KINETIC STUDIES

Advance softwares will be used for data representation and kinetic

modeling.

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