Journal of Environmental Management 219 (2018) 189e207

Contents lists available at ScienceDirect

Journal of Environmental Management

journal homepage: www.elsevier.com/locate/jenvman

Review

Advanced oxidation process-mediated removal of pharmaceuticals

from water: A review
Devagi Kanakaraju a, *, Beverley D. Glass b, Michael Oelgemo
€ ller c
a
Faculty of Resource Science and Technology, Universiti Malaysia Sarawak, 94300, Kota Samarahan, Sarawak, Malaysia
b
Pharmacy, College of Medicine and Dentistry, James Cook University, Townsville, Qld 4811, Australia
c
Discipline of Chemistry, College of Science and Engineering, James Cook University, Townsville, Qld 4811, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Pharmaceuticals, which are frequently detected in natural and wastewater bodies as well as drinking
Received 14 November 2017 water have attracted considerable attention, because they do not readily biodegrade and may persist and
Received in revised form remain toxic. As a result, pharmaceutical residues pose on-going and potential health and environmental
24 April 2018
risks. To tackle these emerging contaminants, advanced oxidation processes (AOPs) such as photo-
Accepted 24 April 2018
Fenton, sonolysis, electrochemical oxidation, radiation and ozonation etc. have been applied to
remove pharmaceuticals. These processes utilize the high reactivity of hydroxyl radicals to progressively
oxidize organic compounds to innocuous products. This review provides an overview of the findings
Keywords:
Removal
from recent studies, which have applied AOPs to degrade pharmaceutical compounds. Included is a
Pharmaceuticals discussion that links various factors of TiO2-mediated photocatalytic treatment to its effectiveness in
Wastewater degrading pharmaceutical residues. This review furthermore highlights the success of AOPs in the
Photocatalysis removal of pharmaceuticals from different water matrices and recommendations for future studies are
Advanced oxidation processes outlined.
© 2018 Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
2. Status of pharmaceutical pollution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
3. Advanced oxidation processes (AOPs) as a tool for the degradation of pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
3.1. Ozonation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
3.2. Fenton and photo-Fenton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
3.3. UV and UV/peroxide processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
3.4. Sonolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
3.5. Electrochemical oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
3.6. Radiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
3.7. Combined AOPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
4. TiO2 photocatalytic degradation of pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
5. Conclusions and future outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

1. Introduction

Pharmaceuticals (drug products) containing active pharma-

* Corresponding author. ceutical ingredients (APIs), despite being designed to treat a variety
E-mail address: [email protected] (D. Kanakaraju).

https://doi.org/10.1016/j.jenvman.2018.04.103
0301-4797/© 2018 Elsevier Ltd. All rights reserved.
190 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207

of ailments in humans and animals, have shown a negative impact

on the environment due to their continuous presence in surface
water, groundwater, urban wastewater and also drinking water. The
past two decades have witnessed extensive research directed to-
wards the presence of pharmaceuticals in the environment and as a
result, these organic compounds are now classified as emerging
contaminants. This interest from the scientific community has
stemmed from advancement in analytical methods for their
detection in environmental samples down to parts per trillion (ng/
L) (Richardson and Ternes, 2011; Sangion and Gramatica, 2016).
Such advancements have allowed for the detection of a variety of
pharmaceuticals in the environment, originating from both human
and veterinary use. Recognizing the presence of pharmaceuticals in
the environment, concerns have been raised to investigate their
behaviour, fate, effects and toxicity as well as potential methods for
their efficient removal from these water sources.
Environmentally concerning groups of pharmaceuticals include
non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, beta- Fig. 1. Statistics of publications (2000e2018) on applications of AOPs for pharma-
ceutical degradation (Scopus database for search “AOPs AND pharmaceuticals” in all
blockers (b-blockers), antiepileptic drugs, blood lipid-lowering
subject areas).
agents, antidepressants, hormones, antihistamines (Khetan and
Collins, 2007) and X-ray contrast media (Jiang et al., 2013),
respectively. Wastewater treatment plants (WWTPs) have been pharmaceuticals followed by an overview of various photochemical
identified as the main source for these pharmaceuticals as they and non-photochemical degradation technologies for pharmaceu-
collect discharges from hospitals, veterinaries, households, in- ticals in (waste)water streams, with important and recent out-
dustries and pharmacies (Destrieux et al., 2017; Lee et al., 2017). comes summarized. Additionally, special attention was given to
Due to the differences in the physicochemical properties of APIs, TiO2 photocatalysis, which has received considerable attention in
the configuration of WWTP facilities and the sewage composition, pharmaceutical abatement.
the efficiency of treatments can vary significantly requiring a broad
range of removal protocols (Fatta-Kassinos et al., 2011a; Luo et al.,
2014; Mompelat et al., 2009; Tarpani and Azapagic, 2018). Several 2. Status of pharmaceutical pollution
recent studies have confirmed the presence of pharmaceuticals in
the influents and effluents of WWTPs (Causanilles et al., 2017; Lin Pharmaceuticals with endocrine disrupting properties (EDCs)
et al., 2018). are emerging as environmental pollutants, which is notable from
The non-biodegradable nature and “pseudo persistence” of legislative actions undertaken by environmental agencies in several
many APIs render conventional biological and chemical treatments countries. The United States Environmental Protection Agency
ineffective, thus leading to an increased presence of the parent (USEPA) has included three pharmaceuticals in their recent
drugs and their metabolites in both, aquatic and terrestrial envi- contaminant candidate list (CCL-3) together with eight synthetic
ronments (Mirzaei et al., 2018; Xiang et al., 2018). For example, hormones and other disinfection by-products and pesticides
antibiotics are known to be not effectively removed by conven- (Richardson and Ternes, 2011). Most APIs and EDCs have however
tional methods. In addition, Phase-II metabolites of parent APIs are remained unregulated, although the European Union (EU) and the
commonly undone, leading to higher concentrations in WWTPs' United States of America (USA) in particular have shown great in-
effluents than their influents (Mirzaei et al., 2018). When these terest in combating the presence of pharmaceuticals in the envi-
incompletely treated effluents are released into the aquatic envi- ronment (Esplugas et al., 2007; Metcalfe, 2013; Tarpani and
ronment and utilized by end users for soil irrigation or amendment, Azapagic, 2018). This has resulted in several directives and frame-
the reclaimed water may impose risks to humans, soil, crops and works such as the community program of research on endocrine
biota (Biel-Maeso et al., 2018). Hence, pharmaceuticals have been disrupters and environmental hormones (COMPREHEND), ecotox-
recognized as important environmental pollutants, necessitating icological assessments and removal technologies for pharmaceu-
the search for effective and advanced technologies to remove them ticals in wastewater (REMPHARMAWATER), environmental risk
from wastewater streams and consequently the environment. assessment of veterinary medicines in a slurry (ERAVMIS) and
Among the water treatment technologies employed thus far, European Directives such as 2013/39/EU and EU 2015/495 and an
advanced oxidation processes (AOPs) present great potential for endocrine disruptor screening program (EDSP) by the USEPA
treating a wide range of emerging contaminants. AOPs involve the (Esplugas et al., 2007; Lofrano et al., 2018; Tarpani and Azapagic,
in-situ generation of highly reactive oxygen species (ROS) with low 2018). In addition, the Food and Drug Administration (FDA) re-


selectivity such as hydroxyl radicals (HO ), H2O2, O3 and superoxide quires an environmental assessment report for APIs that are ex-

-
anion radicals (O2 ), providing pathways of complete mineralization pected to be released into the environment with concentrations
to CO2, H2O and inorganic ions or acids (Dalrymple et al., 2007). 1 mg/L (Nikolaou et al., 2007). These efforts clearly indicate that
AOPs are commonly classified into 2 major groups depending on pharmaceuticals are considered an environmental threat for the
their mode of activation, photochemical and thermal (non-photo- future and therefore methods for their removal from the environ-
chemical) methods. Examples include ozonation, Fenton, photo- ment require immediate attention.
Fenton, photocatalysis, radiation, sonolysis and electrochemical Important sources associated with the presence of pharma-
oxidation. A search on SCOPUS displayed a marked increase in the ceuticals in water bodies include inappropriate disposal of medi-
number of studies on AOP applications in tackling the removal of cations by households, pharmaceutical manufacturers, hospitals
pharmaceuticals, signifying an increase in knowledge in this field of and pharmacies (Ziylan and Ince, 2011). These sources of pharma-
study (Fig. 1). ceuticals in the environment have been extensively reviewed
This review initially focuses on the pollution status of (Kanakaraju et al., 2014a; Kaur et al., 2016). In addition, animal
 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207 191

farming releases veterinary pharmaceuticals to the environment reported that all tested pharmaceuticals were resistant to biodeg-
directly through aquaculture, agricultural runoff and leaching radation in river water under laboratory conditions. In another
(Khetan and Collins, 2007). APIs from human consumption are example, carbamazepine has been reported to be resistant to
mainly excreted in urine and faeces into receiving waters, with biodegradation and thus, its removal from surface water is assumed
levels depending on the dose and individual physiology (Bound and to occur via photodegradation (Donner et al., 2013). The discrep-
Voulvoulis, 2005). Elimination from the human body occurs after ancies in the fate of APIs based on the above studies is due to their
the APIs have been partially or completely converted to water- differing chemical characteristics and other factors such as water
soluble metabolites or, in some cases, without being metabolized. flows, season, natural environmental conditions and simulated
Through sewage systems, pharmaceutical residues eventually conditions in the laboratory.
reach WWTPs. A review article reported the excretion rate of hu- In general, the extent of pharmaceutical removal by biological
man and veterinary pharmaceuticals and their metabolites based process in WWTPs varies greatly between studies, depending on
on therapeutic use (Mompelat et al., 2009). Several metabolites the treatment process, physicochemical properties of these organic
such as clofibric acid, a major metabolite of lipid regulators and two compounds, microbial populations, operational parameters such as
major metabolites of carbamazepine, 10, 11-dihydro-10-11- pH, temperature, sludge retention time, biomass concentration and
dihydroxycarbamazepine and 10,11-dihydro-10,11- hydraulic retention time, respectively (Baena-Nogueras et al., 2017;
epoxycarbamazepine, have already been detected in the environ- Martínez-Alcal a et al., 2017). A study reported that the biological
ment, raising considerable concern. Human or veterinary APIs with degradation from a conventional activated sludge WWTP was
resistance to biological degradation may consequently translate crucial for the removal of diclofenac, naproxen and ibuprofen from
into their persistence when released into water bodies (Ferrari water, with more than 80% removal while ketoprofen showed only
et al., 2003). 51.4% degradation (Martínez-Alcala  et al., 2017). In contrast to this,
The current knowledge considers treated municipal wastewater the removal of carbamazepine was attributed to the adsorption
as contributing significantly to the presence of pharmaceuticals as onto activated sludge (Martínez-Alcala  et al., 2017). Nitrification, a
well as other emerging contaminants (e.g. personal care products, microbial-assisted oxidation in biological wastewater treatment
hormones etc.) since WWTPs are not designed to combat the was indicated to enhance lowering the concentrations of pharma-
resilient and persistent nature of many APIs (Afonso-Olivares et al., ceuticals (Guerra et al., 2014). A recent study, which compared the
2017; Carmona et al., 2014; Schro €der et al., 2016; Su arez et al., aerobic biodegradation of 33 pharmaceuticals (and other personal
2008). For example, the recent inclusions of diclofenac and the care products) between two laboratory settings using freshwater
hormones 17b-estradiol and 17a-ethinyl estradiol into the EU and seawater, revealed that marine microorganisms enhanced
watch list (known as Decision 2915/495) is a result of the in- biodegradation (90%) compared to freshwater (57%) after 28 days of
adequacy of WWTPs to remove these pharmaceuticals (Schro €der incubation (Baena-Nogueras et al., 2017). The study highlighted
et al., 2016). Studies performed on sewage treatment plants in that biodegradation was dependent on sample origin and water
different countries have supported this decision. For example, a salinity. Another fact concerning biological degradation is that APIs
sewage treatment plant in Japan was reported as the main source of belonging to the same therapeutic group may demonstrate
six anti-cancer agents detected in the effluent (Azuma et al., 2015). differing biological degradation rates and adsorption onto sludge.
Another study conducted in one of the largest WWTPs in Southern For example, the biological degradation rate of ibuprofen and
China revealed that twenty-four pharmaceuticals were detected in ketoprofen was much higher (>75%) than that of diclofenac (<25%)
the influent with mean concentrations ranging from 2.3 to 890 ng/ (Salgado et al., 2012).
L, with sulphonamides, sulfamethoxazole, sulfadiazine, sulfame- In contrast to many studies performed on the assessment of
thazine, and trimethoprim being the most commonly detected biological processes applied in domestic or municipal WWTPs for
compounds (Lin et al., 2018). Furthermore, the removal efficiencies pharmaceuticals' removal, there are limited studies on industrial
of pharmaceuticals among WWTPs in different countries varied pharmaceutical WWTPs (PWWTPs), which are known to apply a
due to the nature of the organic compounds, geography, climate variety of treatment methods to their biological units. Biological
(Carballa et al., 2004) and operating conditions (Ziylan and Ince, units (e.g. membrane biological reactor, expanded granular sludge
2011). In some cases, discrepancies occurred within WWTPs in bed or biological contact oxidation) in two PWWTPs in northern
the same country mainly due to the sampling methods (Tran et al., China were reported to be effective in removing 62.0e78.3% of
2018). oxytetracycline, chlortetracycline, and tetracycline in their effluents
When pharmaceuticals enter WWTPs that commonly consist of compared to the concentration in their influents, although tetra-
primary and secondary (and infrequently tertiary) treatment cyclines were still detected in their effluents (Hou et al., 2016).
stages, they can be degraded or adsorbed onto the sewage sludge, As a consequence of incomplete removal from WWTPs, unre-
depending on their physicochemical properties and the operating moved or residual APIs and their metabolites are released into
conditions of the treatment facility (Guerra et al., 2014; Kaur et al., surface waters, groundwater and eventually into the aquatic envi-
2016; Verlicchi et al., 2012). The presence of living organisms such ronment (Xiang et al., 2018). A wide range of pharmaceuticals,
as bacteria and fungi contribute to the degradation of pharma- including anti-inflammatories, analgesics, antibiotics, b-blockers,
ceuticals in WWTPs (MacLeod and Wong, 2010), particularly in the lipid regulators, antiepileptic and antidepressants drugs and hor-
secondary treatment stage (e.g. aerobic or anaerobic systems) mones have been frequently detected in environmental waters (Lee
where biological processes are involved. Nevertheless, biological et al., 2017). Typically, the existence of APIs in surface water,
degradation has been argued to have a minimal effect on the groundwater and drinking water occurs at trace levels ranging from
degradation of pharmaceuticals and this failure has been named as ppt to ppb (ng/L to mg/L) (Kümmerer, 2009b). Numerous in-
a key factor for their biological persistence (Klavarioti et al., 2009) vestigations are available on the occurrence of APIs in surface wa-
and subsequent discharge into the aquatic environment. Contra- ters (Moldovan, 2006; Paíga et al., 2016; Ternes, 1998),
dictory evidence is however available on this aspect in the litera- groundwater (Drewes et al., 2002; Korosa et al., 2016; Lopez-Serna
ture. For example, Heberer et al. (2002) reported that et al., 2013) and sewage influents and effluents (Andreozzi et al.,
biodegradation contributed 99% to the removal of caffeine, but only 2003; Arlos et al., 2015; Carballa et al., 2004; Gros et al., 2017;
8% and 17% for carbamazepine and diclofenac, respectively, from Heberer, 2002; Lindqvist et al., 2005). Detection of metabolites or
sewage treatment plants in Berlin, while Yamamoto et al. (2009) conjugated metabolites in natural waters have also been reported
192 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207

in various studies, signifying the potential impact and risks on presence of diclofenac, propylparaben and ibuprofen in concen-
human health and ecosystems (Azuma et al., 2015; Borgatta et al., trations ranging from 1 to 39 ng/L, while naproxen and salicylic acid
2015). In contrast, studies on the potential impacts of active me- were detected more frequently in 8 sampled tap waters.
tabolites have been rather limited. As water and wastewater containing pharmaceutical residues
Concentrations of pharmaceuticals are generally higher in are becoming a potential threat to the ecosystem and show po-
sewage effluents compared to freshwater bodies or receiving wa- tential toxic effects to humans, destructive methods based on AOPs
ters. This is attributed to natural dilution effects and other natural have been proposed for their elimination.
elimination pathways such as hydrolysis, sorption (or adsorption)
and photolysis by natural sunlight (Pal et al., 2010). Dilution effects, 3. Advanced oxidation processes (AOPs) as a tool for the
which determine the concentration of pharmaceuticals in the degradation of pharmaceuticals
receiving waters, are governed by the wastewater flow from the
WWTPs coupled with water flow in the receiving water (Caliman Reactive oxygen or free radical species represent strong oxidants
and Gavrilescu, 2009). The removal of pharmaceuticals via hydro- that can initiate AOPs in order to degrade pollutants to simple and
lysis appears to be minimal (Ziylan and Ince, 2011), as they are nontoxic molecules. Free radical species are atoms or molecules
commonly designed for oral administration (Andreozzi et al., containing at least one unpaired electron such as the hydroxyl
radical (HO ), superoxide anion radical (O2-), hydroperoxyl radical



2003). In contrast, adsorption of pharmaceuticals onto suspended




solids, sediments and sludge is an important physical process, (HO2) or alkoxyl radical (RO ), with the HO radical having attracted


which subsequently favours their removal in the presence of such the most attention in this area. The characteristic features of HO
materials. However, various factors contribute to the adsorption radicals are their non-selective nature, high reactivity and powerful
capacity of soils or sediments such as soil type, organic matter oxidizing capabilities (Eo ¼ þ2.80 V) (Andreozzi et al., 1999). They
content, clay content and ion-exchange capacity (Drillia et al., are ranked second to fluorine (þ3.03 V) and are able to attack a
2005). Physicochemical properties of the API such as water solu- wide range of organic contaminants, with rate constants normally
bility, octanol-water partition coefficient (log Kow) and soil-water in the order of 106e109 M1 s1 (Andreozzi et al., 1999; Legrini


distribution coefficient (log Kd) are important factors in deter- et al., 1993). Reactions of HO radicals with organic compounds
mining the degree of adsorption (Drillia et al., 2005). Typical can be either by hydrogen abstraction (Eq. (1)) from C-H, N-H, or O-
characteristics of pharmaceuticals such as their low polarity, high H groups, or radical-radical interactions, e.g. the addition of mo-
hydrophilicity and a low log Kow suggest a low binding capacity to lecular O2 leading to the formation of the peroxyl radical (Eq. (2)),
soils, sludge or sediments (Caliman and Gavrilescu, 2009). or through direct electron transfer (Eq. (3)) yielding oxidized in-
The presence of pharmaceuticals in trace quantities has subse- termediates or, in the case of complete mineralization, the pro-
quently resulted in adverse effects in aquatic and terrestrial or- duction of CO2, H2O and inorganic acids (Legrini et al., 1993).
ganisms (Kümmerer et al., 2000; Oaks et al., 2004; Sebestye n et al., Despite the high oxidation potential, kinetic rates of interactions


2018) as well as potential toxicity on non-target organisms or between HO radicals and organic compounds depend on the af-
aquatic environments (Ferrari et al., 2003; Santos et al., 2010). finity of these compounds for the oxidant.
Concerns arising from mixtures of pharmaceuticals are also
HO þ RH / R þ H2O



increasing, despite the focus of most studies on biological effects of (1)
single API compounds. A study by Brodin et al. (2013) revealed that
R þ O2 / RO2



the concentration of the psychotherapeutic drug oxazepam was (2)
significantly higher in the muscle tissue of the European perch
(Perca fluviatilis) from the river Fyris (Sweden) than in the river HO þ RX / RX þ þ HO



(3)
water itself as a consequence of bioaccumulation. Their subsequent
study also reported that oxazepam induced behavioural changes in A considerable amount of work has been published relating to
fish at environmentally relevant concentrations (Brodin et al., the application of AOPs for the abatement of pharmaceuticals in
2014). Grabicova et al. (2017) investigated the bioaccumulation of water. Application of AOPs to wastewater treatment in general has
selected psychoactive pharmaceuticals in different tissues of brown been extensively reviewed (Deegan et al., 2011; Gogate and Pandit,
trout found in a stream affected by the effluents of a WWTP. The 2004; Klavarioti et al., 2009; Wang and Wang, 2016; Wang and Xu,
results revealed that the liver and kidney were the most affected 2012) including specific types of AOPs to pharmaceutical degra-
organs. In addition, the emergence of antibiotic resistant genes and dation such as photocatalysis (Dalrymple et al., 2007), non-thermal
bacteria due to high usages of antibiotics has also been reported plasma treatment (Magureanu et al., 2015) and iron-based catalytic
(Guo et al., 2018; Kümmerer, 2009a; Michael et al., 2013). Another ozonation (Wang and Bai, 2017). A recent review by Ahmed et al.
worrying aspect of these resistant genes is that they can reach (2017) has provided an insight into the impact of various biolog-
humans via the food chain, as shown in the case of lincomycin ical, chemical and hybrid techniques on emerging contaminants
(Wang et al., 2018). Contraceptive pills containing ethinyl estradiol including pharmaceuticals. Recent representative studies on the
have been reported to induce feminization in the male fish and degradation of pharmaceuticals are presented in Table 1. In this
reduced sperm production in downstream of WWTPs (Sebestye n section, major findings of the chosen AOPs, namely ozonation,
et al., 2018). Fenton, photo-Fenton, sonolysis, UV and UV/peroxide oxidation,
The presence of APIs in drinking water (Heberer et al., 2002; electrochemical oxidation and radiation are presented, while TiO2
Jones et al., 2005; Rosa Boleda et al., 2011; Ternes et al., 2002) photocatalysis is discussed in the following section. According to
and groundwater (Lapworth et al., 2012; Yang et al., 2017) as a Table 1, AOPs commonly applied for pharmaceutical wastewater
source of potable water represents an urgent concern although treatment include three types: photochemical processes, non-
there is currently a lack of evidence for a direct link to human photochemical processes and hybrid or combined processes
health impacts. Recycling of potable water has also raised human (Fig. 2).
health concerns. For example, in California and Florida with such
recycling programs, humans may consume water potentially con- 3.1. Ozonation
taining active metabolites and degradants of pharmaceuticals
(Carbonaro et al., 2013). Carmona et al. (2014) reported the Chemical oxidation processes, ozonation and combinations of
 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207 193

Table 1
Overview on selected recent publications on the application of different types of AOPs to the degradation of pharmaceuticals.

AOPs applied Pharmaceuticals Water matrix Significant findings Reference

Single AOP
Ozonation
Antibiotics, steroid Synthetic wastewater, Specific ozone doses ranging from 0.82 to 2.55 mg O3/mg DOC resulted in Almomani
hormone, lipid regulator, surface water, and >99.9% removal for most of the studied pharmaceuticals. The increased et al., 2016
antineoplastic, non-steroidal effluents of municipal toxicity for aqueous solutions of acidic pharmaceuticals at a specific ozone
anti-inflammatory drug, and wastewater dose of 2.24 mg O3/mg DOC was due to formation of more toxic by-
psychostimulant treatment plant products.
Indomethacin Ultrapure water Ozone doses of 2, 10, 20 and 35 mg/L resulted in complete indomethacin Zhao et al.,
(25 mM) degradation within 7 min in contrast to poor mineralization (TOC), 2017
despite extending the reaction time to 30 min.
Propranolol Milli-Q water Complete removal of propranolol was achieved in 8 min. Total organic Dantas et al.,
carbon (TOC) removal did not increase above 5%, despite increased contact 2011
time of 60 min. Low dose ozone was inefficient to improve biodegradability
of ozonated samples.
Tetracycline Deionized water Direct ozonation showed complete degradation of tetracycline with H2O2 Wang et al.,


concentrations with tert butyl alcohol (HO radical scavenger) showing no 2011
effect on the degradation rate. Only 35% of COD removal was attained after
90 min ozonation.
Carbamazepine, diclofenac, Milli-Q water Carbamazepine, diclofenac and trimethoprim degraded completely when a Alharbi et al.,
sulfamethoxazole, and lower dose of ozone was applied, 1.6 mg/L, 2.3 mg/L and 2.8 mg/L, 2016
trimethoprim respectively. However, sulfamethoxazole consumed a higher dose, 4.5 mg/L
and longer time to achieve complete degradation due to the formation of
highly reactive by-products.
Amoxicillin Distilled water and The pseudo-first order reaction rates for amoxicillin by ozonation at pH 3, Kıdak and
ultrapure water pH 7 and pH 10 were 0.064 min1, 0.321 min1and 1.970 min1, Dogan, 2018
respectively, with pH 10 being the optimum one.
Salicylic acid Deionized water Salicylic acid removal was observed to be more significant and rapid at pH 4 Hu et al., 2016
compared to pH 8 and pH 10. At pH 4 and in the presence of 1 mg/L of ozone,
about 95% of salicylic acid was removed.
Ibuprofen, acetyl Secondary effluent Effect of pHs (6.5, 7.0 and 7.5) at a constant temperature, 20OC in the Cai and Lin,
sulfamethoxazole and from wastewater presence of organic matter on the ozonation treatment with an initial 2016
metoprolol treatment plant concentration of 1.5 mg/L showed that metoprolol degraded at the fastest
rate followed by acetyl sulfamethoxazole and ibuprofen at all pHs.
Fenton and photo-Fenton
Photo-Fenton Amoxicillin Distilled water
Complete and rapid oxidation was attained for amoxicillin in the presence  et al.,
Trovo
potassium ferrioxalate complex within 5 min, while for FeSO4 15 min was 2011
required in experiments using a solar simulator.
Solar photo-Fenton Ofloxacin and trimethoprim Ultrapure water Comparison of solar photo-Fenton between acidic pH (pH 2.8e2.9) and Michael et al.,
neutral (unadjusted pH 7) showed that complete degradation of ofloxacin 2012
and trimethoprim was attained likewise at the acidic pH but at a slower
rate. Poor DOC removal was observed for both conditions.
Solar photo-Fenton Nalidixic acid Demineralized water, Although complete degradation was obtained for nalidixic acid, degradation Sirtori et al.,
saline water, and mineralization was slower in saline water and synthetic industrial 2011
synthetic industrial effluent with a compound parabolic collector.
effluent, real
industrial effluent
Solar photo-Fenton 5-Fluorouracil Ultrapure water Solar simulated Fenton-like treatment (Fe3þ/S2O2 8 ) resulted in a higher Koltsakidou
degradation rate and dissolved organic carbon (DOC) removal than Fe3þ/ et al., 2017
H2O2 for the degradation of 5-fluorouracil. The degradation rate and DOC
1
removal under Fe3þ/S2O2 8 was 0.04 min and 40%, respectively while for
Fe3þ/H2O2 system the values were 0.024 min1 and 25%.
Photo-Fenton Antipyrine Aqueous solution Ferrioxalate induced photo-Fenton reaction with UVA-LED was effective to Davididou


degrade antipyrine as a result of the production of more HO radicals in the et al., 2017
system. The complete degradation of antipyrine was obtained after 2.5 min,
while 93% of TOC removal was recorded after 60 min ([H2O2]o ¼ 100 mg/L,
[Fe]o ¼ 2 mg/L and [H2C2O4]o ¼ 100 mg/L, pH ¼ 2.8).
Solar and artificial UV Oxacillin Deionized water Based on the applied factorial design, removal of oxacillin (203 mmol/L) was Giraldo-
photo-Fenton found to be optimum when the concentration of Fe2þ, H2O2 and applied Aguirre et al.,
light power were 90 mmol/L, 10 mmol/L and 30 W, respectively. 2017
Photo-Fenton 15 pharmaceuticals (in Municipal The highest percentage of micro pollutant degradation at 83% was achieved De la Cruz et al.,
combination with other wastewater in the presence of UV (254 nm) using 30 mg/L H2O2 and 2 mg/L Fe(III) at 2013b
micro pollutants) treatment plant natural pH.
Solar photo-Fenton Mixtures of 15 emerging Synthetic water, Mild solar photo-Fenton (Fe ¼ 5 mg/L, H2O2 ¼ 50 mg/L) was efficient to Klamerth et al.,
contaminants (ECs) simulated effluent degrade mixtures of 15 ECs (pharmaceuticals, personal care products, 2010b
wastewater, real pesticides) without any pH adjustments. But, toxicity level increased, with
effluent wastewater the degradation products formed in real effluent wastewater.
Solar photo-Fenton Carbamazepine, ibuprofen, Municipal Solar photo-Fenton using Fe: ethylenediamine-disuccinic acid (1:2) Miralles-
ofloxacin, flumequine, wastewater resulted in >96% removal of pharmaceuticals within 45 min while Fe:citrate Cueuvas et al.,
sulfamethoxazole treatment plant (1:5) produced 94% removal after 96 min at neutral pH using nanofiltration 2014
effluent concentrated sample.
Photo-Fenton Ciprofloxacin Milli-Q water Photo-Fenton degradation of low and high concentrations of ciprofloxacin de Lima Perini
in the presence of different iron sources (iron citrate, iron oxalate and iron et al., 2013
nitrate) and pH (2.5, 4.5 and 6.5) gave different results. For a high
(continued on next page)
194 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207

Table 1 (continued )

AOPs applied Pharmaceuticals Water matrix Significant findings Reference

concentration of ciprofloxacin (25 mg/L) at pH 4.5, both the iron complexes

iron citrate and iron oxalate produced total conversion within 10 min.
Higher ciprofloxacin conversion was obtained using iron citrate for low
concentration (1 mg/L) of this compound at pH 2.5 after 10 min.
UV and UV/peroxide processes
UV and UV/H2O2 41 APIs (10 analgesics, 4 Municipal treatment The removal efficiencies by UV and UV/H2O2 were highly dependent on the Kim et al., 2009
antiarrhythmic agents and plant type of pharmaceutical, while H2O2 addition during the treatment enhanced
12 antibiotics and 15 others) the API removal up to 90% as well as DOC removal.
UV/H2O2 and UV Sulfamethoxazole, Milli-Q water, lake Photolysis rate of all the bioactive compounds using low pressure UV Baeza and
sulfamethazine, water and photolysis (254 nm) differed at pHs tested, while efficiency of UV/H2O2 on Knappe, 2011
sulfadiazine, trimethoprim, wastewater the tested bioactive compounds was as follows:
bisphenol A, and diclofenac treatment plant diclofenac > sulfamethoxazole > sulfamethazine > sulfadiazine > bisphenol
effluent A z trimethoprim.
UV Sulfasalazine, sulfapyridine Milli-Q water Sulfasalazine was resistant to direct UV (254 nm) photolysis while Ji et al., 2018
and 5-aminosalicyclic acid sulfapyridine demonstrated the fastest degradation due to its high molar
absorption coefficient, 15241 M1 cm1.
UV/H2O2 and UVC Amoxicillin Distilled deionized Degradation of amoxicillin by direct UV and UV/H2O2 with a low pressure Jung et al., 2012
water Hg lamp (254 nm) showed that the degradation of 100 mM of amoxicillin
(pH 7, 20  C) followed first-order kinetics and the degradation rate
increased with the H2O2 concentration. An addition of 10 mM H2O2
improved the degradation rate up to six-fold when compared to direct UV.
UV Ketoprofen, carprofen and Ultrapure water and The photolysis kinetics of ketoprofen, carprofen and diclofenac acid Li et al., 2017
diclofenac acid methanol followed pseudo-first order kinetics. Degradation of diclofenac acid was
much slower compared to carprofen and ketoprofen. The predicted toxicity
revealed that the transformation products of ketoprofen were more toxic
than the parent API.
UVC/H2O2 and UVC/ 17a-ethinyl estradiol, 17b- Ultrapure water In the presence of natural organic matter in the UVC/H2O2 system, the Markic et al.,
S2O2-
8 estradiol, azithromycin, degradation rates (kapp) of azithromycin, carbamazepine, dexamethasone 2018
carbamazepine, and 17a-ethinyl estradiol were enhanced between 3% and 11%, while an
dexamethasone, inhibitory effect resulted in the case of 17b-estradiol, erythromycin and
erythromycin and oxytetracycline.
oxytetracycline
UVC/H2O2 Diclofenac Ultra-pure water Diclofenac completely degraded in solution within 2 min under UVC/H2O2 Perisic et al.,
compared to UVA/TiO2, which took 156 min to achieve similar degradation. 2016
A much higher mineralization (TOC) rate constant, 3.92  104 s1 was
obtained from the UVC/H2O2 treatment.
UV Sulfamethoxazole and Deionized water The direct photolysis (UV 254 nm) of sulfamethoxazole and ibuprofen at pH Luo et al., 2018
ibuprofen 3 and pH 7.55 followed pseudo-first order kinetics. The initial reaction rate
of the neutral sulfamethoxazole at pH 3 was 0.9149 min1 higher than
anionic sulfamethoxazole at pH 7.55, 0.3558 min1 in contrast to ibuprofen,
where the initial reaction rate was higher for its anionic form at pH 7.55
(0.0263 min1) than its neutral form at pH 3 (0.0043 min1).
Sonolysis
Ciprofloxacin Deionized water Degradation of ciprofloxacin at frequency 544 kHz (pH 7, 25  C) fitted De Bel et al.,
pseudo-first-order degradation with a half-life of 102 min. Addition of t- 2011
butanol (0.45, 4.5 and 45 mM) slowed down the degradation of
ciprofloxacin confirming that t-butanol acts as a radical scavenger and the


degradation of ciprofloxacin occurred due to the HO radical.
Diclofenac and Milli-Q water and Degradation of diclofenac and carbamazepine followed first-order kinetics. Naddeo et al.,
carbamazepine urban wastewater The reaction rates were observed to increase with increasing power density 2013
treatment plant from 100 to 400 W/L.
Piroxicam Ultrapure water, The reaction rates of piroxicam (640 mg/L) at power density of 20, 36 and Lianou et al.,
bottled water and 60 W/L were 0.1157 min1, 0.1695 min1 and 0.1967 min1, respectively. 2018
surface water
Ibuprofen Ultrapure water Application of single ultrasonic frequencies, 20 kHz, 40 kHz, 200 kHz, Ziylan-Yavas
572 kHz and 1130 kHz to ibuprofen (50 mM) resulted in 0.033 min1, and Ince, 2018
0.035 min1, 0.038 min1, 0.234 min1 and 0.090 min1, respectively,
indicating increasing degradation with frequency. Addition of zero-valent
iron markedly increased ibuprofen degradation even at low single
frequencies, 20, 40 and 200 kHz.
Oxacillin Distilled water Sonochemical process (275 KHz) efficiently degraded oxacillin (47.23 mmol/ Serna-Galvis
L) and eliminated antimicrobial activity in the presence and absence of et al., 2016
additives (calcium carbonate and mannitol).
Diclofenac Milli-Q water The optimum conditions, initial concentration, pH and frequency Guyer and Ince,
ultrasound for DCF degradation was found to be 30 mM, 3.0 and 861 kHz, 2011
respectively. Addition of Fe-containing additives improved diclofenac
elimination in particular with paramagnetic iron oxide nanoparticles.
Mineralization occurred after 60 min of sonolysis in all cases.
Electrochemical oxidation
Diclofenac, Deionized water and When the degradation rates of the four APIs in synthetic wastewater and Loos et al., 2018
sulfamethoxazole, hospital wastewater real wastewater was compared, higher rates were obtained for the latter
iopromide and 17-alpha- treatment plant when current conditions I ¼ 0.9 A, initial concentration, Co ¼ 0.5 mg/L and
ethinyl estradiol flow rate ¼ 500 L/h were used. This was attributed to the consumption of
less oxidative species by organic matter present in real wastewater
compared to those present in synthetic wastewater.
 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207 195

Table 1 (continued )

AOPs applied Pharmaceuticals Water matrix Significant findings Reference

Carbamazepine Demineralized water, Comparison of carbamazepine degradation in tap water, demineralized García-
tap water and treated water and treated municipal wastewater using Nb/BDD anode and 14 mM Espinoza et al.,
wastewater of NaCl showed that electrolysis resulted better performance in 2018
demineralized water (for pH 2 > pH7 > pH 10) followed by tap water and
treated municipal wastewater.
Not stated Wastewater samples BDD-electro oxidation resulted in constant COD decrease in samples rez et al.,
Pe
from a numbered as 55 to 61 with COD ranging from 5000 to 60,000 mgO2/dm3 2017
pharmaceutical when the applied electric charge was increased from 5 to 50 A h/dm3 at a
manufacturing plant constant temperature (25  C).
Radiation
Carbamazepine Deionized water The increase of peroxymonosulfate concentration (mole ratio of Wang and
peroxymonosulfate to carbamazepine from 10:1 to 30:1) increased the Wang, 2018
degradation of carbamazepine from 80% to 100% within 10 min of treatment
time.
Carbamazepine Ultrapure water TOC reduction in carbamazepine solution decreased with increasing H2O2 Liu et al., 2016
concentrations (0e200 mM) at varying irradiation doses. Carbamazepine
solution containing 50 mM H2O2 produced highest TOC removal at 41%
when the irradiation dose was 20 kGy.
Carbamazepine River water and Addition of sulfite ion (SO23 ) prior to the electron beam radiation led to Zheng et al.,
ultrapure water 85.4% of carbamazepine (75 mg/L) degradation in pure water. Sulfite radical 2014

 

( SO3 ), eaq and O were concluded to be a contributing active species for
carbamazepine degradation in the presence of Na2SO3.
Nineteen pharmaceutical Wastewater sample A 5 kGy radiation dose effectively decomposed low initial levels of Reinholds et al.,
compounds from WWTP pharmaceutical compounds (<50 ng/L). The extent of the degradation of the 2017
pharmaceuticals was found to be dependent on the type and concentration
of the compound.
Fluoxetine Ultrapure water Electron beam irradiation yielded 90% degradation of fluoxetine at radiation Silva et al.,
dose of 0.5 kGy whereas doses above 2.5 kGy led to a below detection limit. 2016
Piperacillin Distilled water, The initial value of the calculated radiation chemical yield for the Szabo et al.,
synthetic wastewater degradation of piperacillin was 0.26 mmol/J. Comparison of electron-beam 2018
mediated antimicrobial inactivation in aqueous solution and synthetic
wastewater revealed that the adsorbed dose and degradation products
affected the findings.
Combined AOPs
Ozone/TiO2 solar Mixtures of four Distilled water and Four APIs, atenolol, hydrochlorothiazide, ofloxacin and trimethoprim Marquez et al.,
photocatalysis pharmaceuticals (atenolol, simulated synthetic sequentially treated, by ozonation and solar photocatalytic oxidation 2014
hydrochlorothiazide, secondary effluent revealed that initial ozonation step led to poor removal of TOC (10%), while
ofloxacin and trimethoprim) solution subsequent solar TiO2 photocatalysis improved the TOC removal to 80% and
60% in distilled water and secondary effluent, respectively.
Ultrasound/Fenton Ibuprofen Distilled water and Coupling of Fenton with ultrasound (20 kHz) enhanced the degradation of Adityosulindro
oxidation (sono- effluent from ibuprofen in the presence of 6.4 mM whereby 95% removal was achieved et al., 2017
Fenton) municipal within 60 min and mineralization was also improved under the same
wastewater conditions.
treatment plant
Ultrasound and Diclofenac, Distilled water The combined ultrasound/ozonation process positively enhanced the Naddeo et al.,
ozonation sulfamethoxazole and degradation of three APIs in single and mixed solutions at an ozone flow of 2015
carbamazepine 3.3 g/h after 20 min of treatment time when compared to ozonation alone at
the same flow.
Sonolysis and Diclofenac, paracetamol, Synthetic Sonophotolysis resulted in the highest TOC removal of 91% in the presence Ghafoori et al.,
photolysis (UV/ salicylic acid, pharmaceutical of 900 mg/L H2O2, 80 W ultrasonic power and UV (253.7 nm). Two factors, 2015
H2O2) chloramphenicol etc. wastewater ultrasound power and initial concentration of H2O2 were concluded as
having the most effect based on the three-level BoxeBehnken experimental
design performed.
Sono-photocatalysis Ibuprofen Milli-Q water Sono-biphotocatalysis produced the highest mineralization rate (DOC Mendez-
with TiO2, sono- removal of 98%) with more efficient consumption of H2O2. Initial Arriaga et al.,
photoFenton and degradation rate was 3.50  103 mM/min. 2009
sono-
biphotocatalysis
with TiO2 and Fe2þ
Photocatalytic Diclofenac and amoxicillin Aqueous solution (not Complete mineralization (TOC abatement) was achieved with TiO2 Moreira et al.,
ozonation specified) and urban photocatalytic ozonation for amoxicillin and diclofenac after 30 min and 2015
wastewater 120 min, respectively.
Ozone/TiO2/UVB, UVB/ Mixtures of nine Water (not specified) Ozone/TiO2/UVB (313 nm) yielded the highest TOC removal of 95% within Rivas et al.,
TiO2, O3/UVB and pharmaceuticals 120 min for the pharmaceutical mixtures (each 10 ppm). 2012
single systems (UV,
O3)
Electro-peroxone Venlafaxine Milli Q water, Compared to single ozonation and electrolysis treatment, electro-peroxone Li et al., 2015
secondary effluent efficiently degraded 20 mg/L of venlafaxine within 3 min of reaction time,
from wastewater when the applied current was increased from 50 mA to 300 mA and the O3
treatment plant concentration was fixed at 40 mg/L.
Ozone and ultrasound Amoxicillin Distilled water and Coupling of ozonation and ultrasound resulted in a higher pseudo-first- Kıdak and
ultrapure water order degradation rate of 2.5 min1 at pH and higher TOC removal (45%) Dog an, 2018
than single ozonation treatment with 1.97 min1 at similar pH.
196 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207

Fig. 2. Types of AOPs for pharmaceutical wastewater treatment.

O3 with H2O2 (O3/H2O2), and O3 with UV (O3/UV) have been applied optimal at acidic pH (pH 4) with about 40e50%, compared to only
to pharmaceuticals in water as a single oxidation method or pre- 10e20% under basic conditions (pH 8 and 10), when the molar ratio
oxidation and/or disinfection step before other treatments between ozone and salicylic acid was approximately 3. Although it


(Almomani et al., 2016; Andreozzi et al., 2005; Ikehata et al., 2006; is known that the concentration of HO radicals increases with
Kıdak and Dog an, 2018). Various parameters such as pH, ozone increasing pH, the degradation of salicylic acid was driven by direct
dose and temperature affected the conversion and mineralization ozone oxidation instead (Hu et al., 2016). The effect of ozone dose
of pharmaceuticals in these treatments. The short life time of ozone and pH (acid and neutral) was investigated by Almomani et al.
renders this method to be expensive and its high-energy demand (2016) for the degradation of four groups of pharmaceuticals,
has been identified as a potential drawback for real applications including antibiotics and oestrogen, in three types of water
(Ikehata et al., 2006). matrices (synthetic, WWTP effluent and surface). Compared to
Many studies have reported low mineralizations, despite high synthetic wastewater, a higher ozone dose (222.3 mg/h) was
removal efficiencies of investigated APIs due to persistent by- needed to effect the degradation of pharmaceuticals in WWTP
products formed during ozonation (Almomani et al., 2016). This effluent and surface water due to the presence of natural organic
finding highlights the necessity to evaluate the toxicity before and matter (NOM). The effect of organic matter in secondary effluents
after treatment by ozonation. Low doses of ozone have been re- from two WWTPs (Dihua and Neihu in Taiwan) on the ozonation
ported to achieve complete abatements of target APIs, but with efficiency was determined by comparing the rate constants (Cai
incomplete mineralization rates. A study by Zhao et al. (2017) re- and Lin, 2016). It was concluded that the observed difference in
ported that ozonation resulted in the complete degradation of the the inhibition rate constant was due to functional groups such as
anti-inflammatory drug indomethacin within 7 min using 4 carboxyl, aliphatic hydroxyl and aryl groups present in the organic
different ozone doses (2e35 mg/L), while only 50% of TOC was matter in the Dihua WWTP. Although organic matter in both sec-
removed at the highest ozone dose (35 mg/L) in 30 min. Two ondary effluents displayed a similar reactivity towards ozonation,


studies performed by Dantas et al. (2011) and Wang et al. (2011) discrepancies occurred on their reactivity towards HO radicals,
found that high removals of the APIs, propranolol and tetracy- which subsequently impacted on the inhibition rate.
cline, were achieved. However, TOC or COD (35% after 90 min) Current research showed that the integration of ozonation with
indicated the formation of stable intermediates or in the case of an activated sludge system (Domenjoud et al., 2017) and the
tetracycline, the resistance of the parent API to ozonation. Addition combination of multistage ozonation with aerobic biodegradation
of H2O2 and irradiation have been suggested to enhance the degree (Marcelino et al., 2017) are effective when dealing with real phar-
of mineralization. Toxicity assessments revealed that toxicity of the maceutical wastewater such as raw hospital water and urban
ozonated or ozone-treated solution can be eliminated despite wastewater. These processes are effective in reducing high levels of
incomplete mineralization. organic matter. The high operating costs of ozonation may be
Operation parameters such as pH, dose of ozone, water matrix, overcome by combining this treatment method with other
and presence of organic matter and their effects on the removal technologies.
efficiency of pharmaceuticals have been studied. Alharbi et al.
(2016) suggested that although all four investigated APIs (diclofe-
nac, carbamazepine, sulfamethoxazole and trimethoprim) required
3.2. Fenton and photo-Fenton
different doses of ozone for their degradation, ozonation can be
regarded as an efficient treatment for these compounds. Kıdak and
an (2018) reported the dependence of the ozonation process on The Fenton reaction is based on the use of a mixture of iron salts
Dog
(Fe2þ) and H2O2, generating HO radicals under mild acidic condi-

pH (e.g. pH 3, 7 and 10) in removing amoxicillin. An alkaline pH (pH 2þ

tions (Eq. (4)). The Fe catalyst can be regenerated as shown in Eq.
10) produced the highest reaction rate (1.970 min1) compared to
(5) or through reactions of Fe3þ with other intermediates (Bautista
acidic and neutral conditions due to the formation of higher

et al., 2008).
amounts of HO radicals formed through ozone decomposition. In
contrast, the degradation of salicylic acid was reported to be
Fe2þ þ H2O2 / Fe3þ þ OH þ HO


(4)
 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207 197

Fe3þ þ H2O2 / Fe2þ þ HO2 þ Hþ

(5) 2017). The potential use of iron ligands or complexing agents
such as oxalate, citric acid and ethylenediaminedisuccinic acid has
Both Fenton and photo-Fenton processes have been found to be been investigated when performing photo-Fenton reactions at a
effective for the degradation of pharmaceuticals. Despite having neutral pH (Klamerth et al., 2010a; Miralles-Cuevas et al., 2014).
similar restrictions as the thermal Fenton process, the photo- In addition to working at non-conventional pHs, different
Fenton reactions can be enhanced by UVeVis radiation to initiate sources of iron species have also been investigated to compare their


additional HO radicals (Andreozzi et al., 1999; Legrini et al., 1993). effects on the degradation efficiency of APIs. de Lima Perini et al.
Solar photo-Fenton has been demonstrated for the treatment of (2013) investigated the potential of iron citrate, iron oxalate, and
various pharmaceuticals such as antibiotics, anti-inflammatory, iron nitrate on the conversion of ciprofloxacin. Iron citrate and iron
analgesic and antineoplastic drugs (Alalm et al., 2015; Klamerth oxalate resulted in the highest conversion of ciprofloxacin (25 mg/
et al., 2010b; Sirtori et al., 2011; Trovo  et al., 2011). For example, L) at pH 4.5, but iron citrate was superior based on the highest TOC
Trovo et al. (2011) reported on the efficiency of photo-Fenton using removal (0.699). A low reactivity between iron nitrate and H2O2
a solar simulator for the degradation of amoxicillin in the presence was suggested to be the cause of the poor degradation of
of two different iron species, ferrioxalate complex and FeSO4. ciprofloxacin.
Complete removal of amoxicillin was achieved in the presence of Overall, researchers are constantly investigating approaches to
the ferrioxalate complex within 5 min, while 15 min were needed overcome the low acidic condition requirements of Fenton and
when FeSO4 was applied in the presence of 120 mg/L H2O2. photo-Fenton reactions. By modifying ‘conventional’ conditions, a
Nevertheless, the ferrioxalate complex was found to demonstrate better insight in the efficiency is obtained and sluggish degradation
higher toxicity particularly for Daphia magna bioassays. Low con- kinetics are overcome. However, more studies need to be per-
centrations of Fe2þ (5 mg/L) and H2O2 (75 mg/L) have been shown formed and optimized at a wide pH range using natural and
to efficiently degrade 100 mg/L of loxacin and trimethoprim under wastewater matrices.
solar photo-Fenton conditions (Michael et al., 2012). Sirtori et al.
(2011) performed the solar photo-Fenton on nalidixic acid in 3.3. UV and UV/peroxide processes
different water matrices (i.e. demineralized water, saline water and
simulated industrial effluent). The efficacy of the solar photo- The effectiveness of UV processes for the removal of pharma-
Fenton process was greatly affected by the water composition, in ceuticals depends strongly on the UV absorption of the pharma-
particular for DOC removal. DOC removal from the simulated in- ceutical (Kim et al., 2009). The critical parameters determining the
dustrial effluent was the lowest with 20% after 240 min, followed degradation kinetics of direct UV photolysis furthermore comprise
by 73% reduction in the saline water after 107 min and 86% in the the rate constants, kUV, quantum yield (4), and molar extinction
demineralized water after 92 min. Koltsakidou et al. (2017) coefficient (ε) (Luo et al., 2018). UV combined with H2O2 (UV/H2O2)
explored the solar photo-Fenton (Fe3þ/H2O2) degradation of 5- generally provides better removal efficiencies for pharmaceuticals
fluorouracil by varying the concentrations of H2O2 (0e90 mg/L) with poor UV absorption. UV/H2O2 processes are governed by the
and Fe3þ (0e15 mg/L). At pH 3, the optimum concentrations of

H2O2 concentration, rate of HO radical formation, UV light in-
H2O2 and Fe3þ were 60 mg/L and 4.5 mg/L, respectively. This study tensity, water constituents, chemical structure of the pharmaceu-
chose a lower concentration of Fe3þ, 4.5 mg/L, despite the higher tical (Yuan et al., 2009) and also the solution pH (Baeza and Knappe,
concentration providing a slightly higher degradation rate, due to 2011).
the increased need for iron sludge removal if a higher concentration A study of UV photolysis (254 nm) revealed that sulfasalazine
were to be applied. was photostable, while this technique was able to degrade its two
A recent study has reported that a ferrioxalate-based photo- human metabolites, sulfapyridine and 5-aminosalicylic acid. The
Fenton reaction using UVA-light emitting diodes (LEDs) success- reported quantum yields for sulfapyridine and 5-aminosalicylic
fully led to complete degradation of antipyrine in 2.5 min, 93% of acid were (8.6 ± 0.8)  103 and (2.4 ± 0.1)  102 mol Einstein1,
TOC removal in 60 min and a reduction in the amount of H2O2 respectively. However, addition of peroxides, H2O2 and perox-
(Davididou et al., 2017). The near monochromatic irradiation at ydisulfate to the UV system attained 93.1% and 96.2% removal of


365 nm, which was close to the maximum absorbance of the fer- sulfasalazine as a result of the highly reactive free radicals HO and


rioxalate complexes, was suggested to be the crucial factor SO4 (Ji et al., 2018). A study by Jung et al. (2012) also reported an
(Davididou et al., 2017). A minimal amount of H2O2 (100 mg/L) was enhanced degradation rate when amoxicillin was degraded with
found optimal to degrade 50 mg/L of antipyrine. Excess H2O2 UV light in the presence of 10 mM of H2O2, compared to direct UV


exhibited scavenger effects thus reducing the availability of HO alone. A study by Li et al. (2017) reported on the degradation rates
radicals needed for API degradation (Veloutsou et al., 2014). of three non-steroidal anti-inflammatory drugs (NSAIDs), keto-
Although the Fenton process is not as energy intensive as other profen, diclofenac and carprofen when exposed to UV irradiation
AOPs such as UV and O3, it requires low acidic pH (3e5) conditions (254 nm). Results indicated that carprofen exhibited the highest
(Malato et al., 2002) with pH significantly influencing the Fenton degradation rate of 1.54  104 s1, followed by ketoprofen at
reaction (Perini et al., 2018). At a pH higher than 3, Fe3þ precipitates 5.91  105 s1 and diclofenac at 7.78  106 s1. A recent study by
as Fe(OH)3, while at even higher pH values, the formation of Fe(II) Markic et al. (2018), which compared the effectiveness of UVC/H2O2
complexes leads to a decline in Fe2þ concentration. Much progress and UVC/S2O2 8 treatments on the degradation of 17a-ethinyl
has been made in operating Fenton and photo-Fenton processes at estradiol, 17b-estradiol, azithromycin, carbamazepine, dexameth-
a neutral or near-neutral pH to deal with large-scale operations or asone, erythromycin and oxytetracycline in a mixture (in the
real wastewater samples (e.g. hospital wastewater) (Giraldo- absence of NOM), revealed that first-order reaction rates for UVC/
Aguirre et al., 2017; Perini et al., 2018). The removal of oxacillin S2O2
8 were higher than UVC/H2O2. The observed results were
attributed to the different reaction mechanisms of the HO and SO4-



was performed at pH~6 (Giraldo-Aguirre et al., 2017), while the
removal of mixtures of micropollutants by means of photo-Fenton radicals with the pharmaceuticals and also due to the discrepancies
was performed at pH 6e7 (De la Cruz et al., 2013b). A 203 mmol/L in their optical properties (e.g. quantum yield and molar absorption
solution of oxacillin was completely eliminated after 50 min in the coefficients).
presence of 90 mmol/L of Fe2þ, 10 mmol/L of H2O2 and irradiation A study by Perisic et al. (2016) compared the efficiency of UVC/
with a 30 W light source (365 nm) at pH 6 (Giraldo-Aguirre et al., H2O2 with UVA/TiO2 for the degradation of diclofenac. Complete
198 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207

degradation of diclofenac (29.62 mg/L) was achieved within 2 min these additives did not alter the degradation kinetics of oxacillin
under UVC/H2O2 conditions (H2O2 ¼ 16.78 mM), which was sub- and the antimicrobial elimination kinetics, confirming the effec-
stantially faster compared to UVA/TiO2 (TiO2 ¼ 1.306 g/L), which tiveness of sonolysis to selectively degrade pharmaceuticals and to
took 156 min. UVC/H2O2 also resulted in a higher pseudo-first- eliminate antibiotic activity, even in the presence of other phar-
order rate constant for mineralization (3.92  104 s1), while for maceutical ingredients. The obtained degradation rates for an
UVA/TiO2, the rate constant was 8.72  105 s1. The effects of the initial concentration of 47.23 mmol/L oxacillin and 250 kHz of ul-
molar extinction coefficient (ε), quantum yield (4), and degradation trasound for oxacillin only, oxacillin and mannitol and oxacillin and
kinetics of ibuprofen and sulfamethoxazole was examined at calcium carbonate showed similar values of 1.4 ± 0.0, 1.3 ± 0.1, and
varying pHs (3 and 7.55) and by employing experimental and 1.4 ± 0.1 mM min1, respectively, while the antimicrobial kinetics
modelling approaches (Luo et al., 2018). The 4 values for ibuprofen were 0.0145, 0.0144, and 0.0146 min1, respectively. Another study
at pH 3 and 7.55 were 0.0161 and 0.1030 mol Einstein1, respec- investigated the effect of the addition of Fe-containing additives,
tively, while for sulfamethoxazole the values were 0.0885 and namely Fenton's reagent, zero-valent iron and super paramagnetic
0.0236 mol Einstein1, respectively. The discrepancies of the 4 iron oxide nanoparticles, on the sonochemical degradation of
values obtained in this study compared to other existing studies diclofenac (Guyer and Ince, 2011). Among the three Fe-additives,
were attributed to the experimental conditions such as the volume super paramagnetic iron oxide nanoparticles produced the high-
and geometry of the reactor and the light source. The developed est estimated relative efficacy, 41.54 mM mg1 at a frequency of
model was suggested to be used in optimizing photolysis effects on 861 kHz due to the large surface area and excess cavitation nuclei,
pharmaceuticals at different pHs and in real wastewater. confirming the contribution of paramagnetic iron oxide nano-
As UV photolysis is highly dependent on the chosen irradiation particles in ultrasound treatment.
intensity, the response of APIs and the quantum yield, the addition Although sonolysis principally does not require additional
of peroxides to generate reactive radicals has been shown to chemicals, this technique is rather energy demanding, results in
improve the degradation of APIs. UV/H2O2 has also shown to reduce low mineralization and is limited to lab-scale. To overcome these
the required UV energy in accomplishing degradation of pharma- drawbacks, it may be coupled with other AOPs to reduce the
ceuticals (Kim et al., 2009), as the degradation is no longer operating costs and to benefit from the synergistic effects of the
dependant on direct absorption by the API. AOPs for both, API oxidation and mineralization. The mechanisms
involved in the degradation of pharmaceuticals should be further-
3.4. Sonolysis more established to elucidate the contribution of the chosen AOP to
sonolysis.
Another AOP which has gained popularity is ultrasound irradi-
ation, also known as sonolysis. This technique is based on the 3.5. Electrochemical oxidation


production of HO radicals from water pyrolysis due to the high
intensity of acoustic cavity bubbles (Guyer and Ince, 2011). Electrochemically-based AOPs have appeared as an attractive
option for pharmaceutical removal as they generate reactive spe-
H2O þ))) / HO þ H



(6) cies via electricity and without the need for chemicals and thus
without secondary waste (Garcia-Segura et al., 2018). A review by
2 HO / H2O2 Sires and Brillas (2012) highlighted research findings related to this


(7)
technology, which can be classified as electrochemical separation
2 HO / H2O þ O


(8) technologies (such as electrodialysis and electrocoagulation) and
degradation technologies (such as anodic oxidation). Two oxidation
where))) refers to the ultrasound irradiation. mechanisms are involved in the electrochemical oxidation process.
The efficiency of this AOP to degrade APIs is significantly Firstly, there is the direct oxidation at the anode whereby direct
affected by the power and frequency of the applied ultrasound charge transfer occurs between the pharmaceutical compound and
(Ince, 2018; Kıdak and Dog an, 2018; Me ndez-Arriaga et al., 2008b). the anode surface. Indirect oxidation occurs via in-situ generation
The influence of frequency on the degradation of ciprofloxacin has of reactive oxygen species by oxidants at the surface of the elec-
been studied (De Bel et al., 2011). The results obtained revealed that trode (Feng et al., 2013).
among the three frequencies investigated (544, 801 and 1081 kHz), Compared to conventional anodes such as Pt, IrO2 or PbO2,
the lowest at 544 kHz produced a high degradation rate constant of boron-doped diamond (BDD) anodes are popular in the electro-
0.0067 min1 when degrading 15 mg/L of ciprofloxacin at 25  C. chemical oxidations of pharmaceuticals due to their stability to


Naddeo et al. (2013) reported that increasing the power density corrosion, high oxygen-over potential (to generate more HO radi-
(100e400 W/L) successfully enhanced the degradation of diclofe- 
cals) and inert surfaces (García-Espinoza et al., 2018; Svorc et al.,
nac and carbamazepine. Likewise, a recent study by Lianou et al. 2017). Several studies have confirmed the effectiveness of BDD
(2018) also reported that the investigated power densities anodes in degrading pharmaceuticals. The degradation of diclofe-
(20e60 W/L) enhanced the degradation of piroxicam, due to the nac, sulfamethoxazole, iopromide and 17-alpha-ethinylestradiol in


formation of HO radicals and higher mixing intensity. Furthermore, a real hospital effluent and in synthetic wastewater was compared
cavitational activity also critically controls the efficiency of sono- using electrochemical oxidation with a BDD anode (Loos et al.,
chemical treatment (Ziylan-Yavas and Ince, 2018). Ultrasonic power 2018). Flow rates (125, 250 and 500 L/h) did not significantly
increases the degradation rate linearly as a result of the high affect the pseudo-first-order rate constants for sulfamethoxazole
number of active cavitation bubbles, subsequently generating more and iopromide, while the rate constants increased for diclofenac
and 17-alpha-ethinylestradiol with increasing flow rate in the


HO radicals (Madhavan et al., 2010).
The addition of radical promoters also contributes to the per- simulated wastewater at an applied current of 0.9 A. In the real
formance of sonolysis (Rayaroth et al., 2016). The effects of other hospital wastewater, an increase in the applied current from 0.9 to
pharmaceutical ingredients or additives such as mannitol and cal- 3.1 A positively enhanced the degradation of all four compounds
cium carbonate on the ultrasound degradation of oxacillin and instead. Degradation of carbamazepine was greatly influenced by
elimination of antimicrobial activity were investigated by Serna- current and treatment time applied during the electrochemical
Galvis and co-workers (Serna-Galvis et al., 2016). The addition of degradation mediated by chloride ions and using a Nb/BDD anode
 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207 199

(performed better than Ti/IrO2) (García-Espinoza et al., 2018). Acute management in a wastewater treatment plant. This has been
toxicity testing using Vibrio fischeri showed an increase in toxicity demonstrated by Szabo  et al. (2018) for the elimination of the
levels after 20 min and 90 min of treatment time from 11.35 TU antimicrobial activity of piperacillin present in an environmentally
(toxicity unit) to 30.44 TU. This was linked to residual reactive relevant concentration.
chlorine species and not to any toxic by-products. Electrochemical Radiation has been reported as a clean process as there is no
oxidation using BDD was also reported to be more efficient than requirement of additional chemicals to initiate the reaction, the
Fenton oxidation in degrading real pharmaceutical wastewater energy cost is minimal and the process can be performed at various
sampled from a pharmaceutical plant, due to its reliability and temperatures (Darwis et al., 2015; Kim et al., 2017). Beside the
robustness (Pe rez et al., 2017). degradation kinetics deriving from radiation-induced degrada-
Although electrochemical oxidation is known for its advantages, tions, studies should focus on the radiolytic degradation products,
the effectiveness of electrochemical processes is greatly controlled mineralization and also toxicity, which have been generally lacking
by the electrode surface whereby it tends to reduce over-treatment in the above studies. In addition, the potential ionizing irradiations
as a result of the formation of products. Research should be directed such as electron-beam radiation and gamma radiation should be
towards the fabrication of novel electrodes to overcome such lim- investigated at environmentally-relevant concentrations.
itation and more studies are needed on pilot scale rather than
commonly conducted lab-scale scales. 3.7. Combined AOPs

3.6. Radiation Although the treatment of pharmaceuticals typically revolves

around single AOP methods, recent developments in AOP hybrid
A recent review has shown that solution pH, dose rate and water techniques have attracted considerable interest. Hybrid AOPs have
matrices contribute to the effectiveness of ionizing irradiation in been studied in various combinations as shown in Fig. 2 and Table 1.
degrading pharmaceuticals and personal care products (Wang and The increased removal of pharmaceuticals in hybrid systems
Chu, 2016). Compared to UV-based AOPs, gamma irradiation has compared to single AOP is due to the synergistic effect and the
shown better penetration and subsequently increased formation of increase in the amount of reactive species, which also produces
hydroxyl radicals and hydrated electrons (e aq) to facilitate the better mineralization. To maximize the degradation efficiency, APIs
degradation of pharmaceuticals. Wang and Wang (2018) investi- in real or synthetic wastewaters are either treated sequentially or
gated single gamma irradiation to induce activation of perox- simultaneously.
ymonosulfate for the degradation of carbamazepine. Although The combinations of AOPs, choices of AOPs and orders of
increasing the dose of single gamma irradiation resulted in treatment vary from study to study and there is no clear agreement
increased degradation of carbamazepine, the addition of perox- on this aspect. M arquez et al. (2014) performed ozonation to treat
ymonosulfate caused its complete degradation, attributed to the pharmaceutical wastewater followed by solar TiO2 photocatalytic
presence of hydroxyl radicals, perhydroxyl radicals and superoxide oxidation. Although substantial TOC removal (60% for synthetic
radical anions. Another study on carbamazepine investigated the secondary effluent and 80% for distilled water) was observed
efficiency of combining electron beam irradiation and hydrogen compared to the single treatment, the study failed to justify the
peroxide (Liu et al., 2016). The authors revealed that a degradation order of the treatment and it was recommended to pursue an
of carbamazepine of up to 90% could be achieved using an electron investigation of both techniques simultaneously. Coupling of ul-
beam irradiation dose of 1 kGy in the absence of H2O2. In the trasonic and Fenton was performed by Adityosulindro and co-
presence of 10 mM of H2O2, the degradation increased to 95%. A workers to remove and improve TOC removal of ibuprofen in
further increase of the H2O2 concentration to 50 and 200 mM led to distilled water and municipal wastewater from a treatment plant
a decrease in the degradation rate, indicating that an appropriate (Adityosulindro et al., 2017). Combinations of sonolysis with
concentration of H2O2 is essential. Zheng et al. (2014) also inves- ozonation and photolysis have also been examined. For diclofenac,
tigated the efficiency of electron beam radiation on the degradation carbamazepine and sulfamethoxazole, Naddeo et al. (2015) studied

of carbamazepine in the presence of different ions (e.g. SO2
4 , HCO3 , the effect of ultrasound introduction on an ozonation system at
NHþ  þ
4 , Cl and Na ) and water matrices. Among the active species, varying flow rates of ozone (e.g. 1.3 g/h, 2.4 g/h and 3.3 g/h).
HO , H and e




aq, HO was determined as the most contributing Although an enhancement was observed in the removal percent-
species based on experiments performed using carbamazepine age, the applied ozone flow rate markedly affected the removal
solutions saturated with either N2, N2O or tert-butanol with N2. efficiencies for the single APIs as well as their mixtures. The
Degradation of carbamazepine in river water both, in the presence application of ozonation in combination with ultrasound enhanced
and absence of suspended solids was slower than in pure water, the degradation of APIs due to the improved ozone mass transfer,
when the adsorbed dose was varied from 0 to 5 kGy due to the but depended on the hydrophobicity of the compound. A study
presence of dissolved organic matter and ions. investigated the potential of sonolysis and photolysis (UV/H2O2),
The effect of two types of ionizing radiation on the degradation referred to as sono-photolytic, for the degradation of synthetic
of multi-class pharmaceuticals in an influent of a WWTP was pharmaceutical wastewater (mainly comprising of chloramphen-
studied by Reinholds et al. (2017). Comparing electron beam radi- icol, diclofenac, salicylic acid, and paracetamol) by measuring TOC
ation and gamma radiation, the former was found advantageous in levels (Ghafoori et al., 2015). Sono-photolysis led to 91% TOC
reducing these pharmaceuticals, as noted from a reduced exposure removal compared to only 3% under sonolysis alone and 8% under
time of more than 35 times. Silva et al. (2016) examined the photolysis (UV) alone, respectively. The preference of combining
degradation of fluoxetine by means of electron beam irradiation sonolysis with other AOPs is mainly driven by the aim to increase
and found that a low irradiation dose, 0.5 kGy, was sufficient to the mineralization level, which is not readily achieved using
achieve almost 90% removal, despite an incomplete mineralization sonolysis alone (Me ndez-Arriaga et al., 2009; Naddeo et al., 2015).
(12.5%) at a similar dose. The acute toxicity for Daphnia similis The combination of ozonation with TiO2 photocatalysis also facili-
(86.8%) compared to only 9.6% for Vibrio fischeri was linked to re- tated complete mineralization for amoxicillin and diclofenac
sidual amounts of the parent compound fluoxetine and not of any (Moreira et al., 2015). The same effect was reported by Rivas et al.
by-products. Electron beam treatment (using a linear electron (2012) for the combination of ozone/TiO2/UVB for the degrada-
accelerator) has proved successful in antibiotic resistance tion of pharmaceutical mixtures. Furthermore, electro-peroxone
200 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207

that combines ozonation and electrolysis treatment also effectively kinetics of the chosen APIs (Kanakaraju et al., 2014b; Van Doorslaer
degraded venlafaxine and provided better TOC removal when et al., 2012; Villegas-Guzman et al., 2015) while studies that only
compared to ozonation only (Li et al., 2015). focused on selected parameters are also available (Fukahori et al.,
As the majority of hybrid and integrated techniques perform 2012; Giraldo et al., 2010) (Table 2). It is widely accepted that the
superior compared to single treatments, more studies are being design and geometry of the photoreactor used also effects the
directed towards this area of research (Table 1). Although it is degradation rate of APIs (Carbajo et al., 2016; Friedmann et al.,
evident that various AOPs are efficient in removing pharmaceuti- 2010; Malato et al., 2009). Variations in these numerous parame-
cals, most AOPs are generally labelled as expensive methods. To ters within different studies make a direct comparisons of results
overcome this drawback, the coupling of advanced oxidation difficult, even for the same API.
treatment with existing conventional water treatment methods has The effects of initial concentrations, TiO2 P25 concentration,
been suggested to be more cost-effective and also to enhance the stirring speed, temperature, and sparging rates (oxygen, nitrogen
€der et al., 2016).
efficiency of the process (Oller et al., 2011; Schro and pure air) were examined for the degradation of moxifloxacin
Coupling of AOPs has been reported to improve the quality of the (Van Doorslaer et al., 2012). The study concluded that photo-
effluent prior to discharge into the environment, as shown by a catalytic degradation of moxifloxacin can generally occur at
recent study that found “safer” effluent when ozone and sonolysis ambient temperature upon sparging, with the other parameters
were coupled for the degradation of amoxicillin in water (Kıdak and greatly influenced the degradation rate. A study by Villegas-
Dogan, 2018). Guzman et al. (2015) reported that the applied light power (30 W
In most of the hybrid studies summarized above, the order of and 150 W) had a significant effect on the degradation kinetics of
the coupled treatment was neither specified nor justified in the dicloxacillin at low TiO2 concentrations (0.05 g/L), while natural pH
experimental section. Future studies should provide a justification enhanced the degradation rate in contrast to acidic (pH 3) or basic
to help with the selection of multiple treatment combinations for pHs (7 and 9), which inhibited the degradation. The effect of
pharmaceutical wastewater treatment. Although coupled AOPs various operational parameters such as TiO2 loading, solution pH,
provide better mineralization, studies should support this finding TiO2 type, type of water, and initial concentration of diclofenac
by identifying intermediates to ascertain that the coupled AOP- were systematically investigated for the degradation of diclofenac
effluent possesses minimal or less environmental risk than the by Kanakaraju et al. (2014b). The water matrix significantly affected
single AOPs. the degradation of diclofenac, due to the presence of ions and other
NOM.
4. TiO2 photocatalytic degradation of pharmaceuticals The material properties of TiO2 such as surface, electronics and
structure also play an important role in governing the overall
Photochemical degradation of pharmaceuticals by means of photocatalytic activity (Carbajo et al., 2016). The choice of the TiO2
TiO2 photocatalysis is undertaken (i) to investigate the kinetics and type also varies between studies with demonstrated differences in
optimize the conditions of the applied process, (ii) to determine photocatalytic activity towards organic compounds. Variations in
mineralization of the parent compound and to achieve high photocatalytic performance are explained by the differences in the
biodegradability, (iii) to identify possible degradation products morphology, crystal phase, specific surface area, surface charge,


formed during HO radical mediated treatment and (iv) to evaluate particle size distribution, porosity, band gap and surface hydroxyl
the toxicity of the treated water to ensure safety. With these four density control (Carp et al., 2004). TiO2 P25, Hombikat UV 100 and
general aims, the application of TiO2 photocatalysis for the removal Ti (IV) oxide (Aldrich) have been commonly used. Table 3 displays a
of various APIs has been examined extensively. Studies using UV/ comparison of the properties of these common photocatalysts. The
TiO2 catalyzed oxidation on different therapeutic drug classes such efficiency of five different TiO2 materials, namely P90, P25, Hom-
as NSAIDs and analgesics, antibiotics, anticonvulsants, lipid regu- bikat UV 100, PC500 and ST01, was tested for the degradation of
lators, b-blockers and psychiatric drugs are summarized in Table 2. carbamazepine (Carabin et al., 2015). The most efficient photo-
Important aspects observed in these studies are also summarized in catalyst was P90 followed by P25 with removal efficiencies of 69%
this section. and 60%, respectively. Mixtures of crystalline phases of anatase and
TiO2 photocatalysis has resulted in the successful degradation of rutile in these photocatalysts were attributed to the observed
a variety of drugs treated, thus leading to an increasing interest in photocatalytic activity. Another study investigated the effect of
its application for the removal of pharmaceuticals in water and eight different TiO2 materials, namely Degussa P25, Hombikat UV
wastewater. The API selection in most studies is either driven by 100, Millennium PC50, Millennium PC100, Millennium PC105,
their high consumption, which correlates with the high probability Millennium PC500, Tronox AK1 and Aldrich Anatase AA, on the
of detection in the environment, or by an existing gap or scarcity of degradation of the antibiotic amoxicillin (Dimitrakopoulou et al.,
available studies on these compounds. For example, antibiotics (e.g. 2012). P25 resulted in maximum API degradation, which was
sulfamethoxazole, amoxicillin, tetracycline) and NSAIDS (e.g. linked to its slower electron-hole recombination rate and its
diclofenac, ibuprofen, naproxen) are frequently investigated due to favourable composition of anatase and rutile. A recent study
their high consumption rates (Kanakaraju et al., 2015; Pereira et al., investigated the degradation of paracetamol and aspirin mixtures
2014; Zhu et al., 2013), while the removal of psychotropic drugs in deionized water using micro-sized TiO2 K1077 (by Kronos) and
such as benzodiazepines and antidepressants represents a knowl- TiO2 P25 (Bianchi et al., 2017). P25 provided complete degradation
edge gap, despite their increased usage (Trawin  ski and Skibin
 ski, (after 6 h) and a mineralization efficiency of 90% (after 6 h). In
2017). contrast, TiO2 K1077 demonstrated a lower photocatalytic activity
TiO2 photocatalytic studies frequently investigate the effects of particularly for aspirin and a poor mineralization of 40% after 4 h.
operational parameters such as catalyst loading, initial concentra- The different properties of these TiO2 materials did not correlate to
tion of substrate, type of TiO2 photocatalyst, pH of the solution, these findings. While TiO2 K107 was composed of a larger crystal-
wavelength/light intensity and water matrix on the degradation line size (130 nm) and anatase/rutile composition (100%), it shows a
kinetics of the pharmaceutical (Carbajo et al., 2016). Besides these lower band gap (3.15 eV) compared to TiO2 P25 (3.21 eV).
common parameters, effects of stirring speed, temperature and gas The influence of the water quality on TiO2 photocatalysis is
sparging rates were also examined. Several studies comprehen- critical to establish its suitability for real wastewater treatment.
sively investigated the effect the operational parameters on the Pharmaceuticals, spiked in distilled water and Milli-Q water, are
 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207 201

Table 2
Selected recent studies of TiO2 photocatalytic oxidation of pharmaceuticals.

Therapeutic class/ Water matrix Experimental conditions Results Reference

compound

Antibiotics
Oxolinic acid Milli-Q water Black lamp (14 W/m2; Experimental conditions of pH 7.5 and 1.0 g/L of TiO2 favoured Giraldo et al.,
365 nm) between 80 and 100% of oxolinic acid degradation. About 20% of 2010
oxolinic acid was adsorbed on TiO2 under dark conditions.
Trimethoprim Milli-Q water, distilled water Solar simulator (1.5 kW Trimethoprim demonstrated high stability to direct photolysis Sirtori et al., 2010
and simulated seawater Xenon arc lamp) and and degradation did not follow first-order kinetics. Solar TiO2
compound parabolic collector photocatalysis improved the degradation of trimethoprim with
rate constants of 0.22 min1 in distilled water and 0.081 min1
in simulated seawater.
Amoxicillin Ultra-pure water and UVA lamp (9 W; 350 Photocatalytic degradation of amoxicillin (10 mg/L) consumed Dimitrakopoulou
secondary effluent from a e400 nm) only 20 min in ultra-pure water compared to 60 min in spiked et al., 2012
municipal WWTP secondary effluent at pH 7.5.
Moxifloxacin Deionized water UVA lamp (365 nm) Maximum degradation rate of moxifloxacin was achieved in the Van Doorslaer
presence of 5 g/L TiO2 and air sparging of 60 mL/min. Ambient et al., 2012
temperature (298 K) was reported to be sufficient for
degradation of this compound.
Dicloxacillin Distilled water Black lamp (30e150 W; Effects of TiO2 concentration and power were investigated on Villegas-Guzman
365 nm) the removal of low (3 ppm) and high (800 ppm) concentration et al., 2015
of dicloxacillin. Degradation rates increased with the TiO2
loadings (0.05e2.0 g/L) and applied power. Highest dicloxacillin
removal rate, 62.82  108 M s1 was obtained using 2 g/L TiO2
and 150 W for 800 ppm.
NSAIDs and analgesics
Diclofenac (and Milli-Q water Solar simulator (250e765 W/ TiO2 photocatalysis produced 96% degradation of diclofenac at Kockler et al.,
amoxicillin) m2) an irradiation level of 400 W/m2, while 80% was achieved with 2012
direct photolysis.
Naproxen (and Distilled water, river water Medium pressure Hg lamp TiO2 photocatalytic degradation rate of naproxen in river water Kanakaraju et al.,
diclofenac) and drinking water (200e600 nm) decreased from 0.21 min1 to 0.10 min1 and 0.11 min1 when 2015
phosphate alone and mixture of phosphate and chloride anions,
respectively was added into river water samples.
Ibuprofen Ultra-pure water Medium pressure Hg lamp Degradation of ibuprofen was more pronounced under TiO2 Candido et al.,
(125 W) photocatalysis using artificial UV light compared to solar UV 2016
irradiation. 92% of ibuprofen was removed, while TOC removal
of 78% was obtained under artificial UV light (medium pressure
Hg lamp).
Aspirin and Milli-Q water and tap water UVA lamp (315e400 nm; The photocatalytic degradation of aspirin and paracetamol Bianchi et al.,
Paracetamol 75 W/m2) mixture (12.5 mg/L each) using 0.1 g/L TiO2 P25 produced better 2017
removal and mineralization compared to similar amount of TiO2
K1077.
Ibuprofen Ultrapure water, municipal UV-LED (4  10 W; 382 nm) TiO2 photocatalytic degradation of ibuprofen in ultrapure water Jallouli et al.,
wastewater and (60 mg/L) increased with the number of LEDs used whereby 2018
pharmaceutical industry 4LEDs produced complete degradation after 30 min of
wastewater treatment time.
Anticonvulsants
Carbamazepine (and Milli-Q water and wastewater Solar simulator (1000 W) Degradation under UVA irradiation in pure water was sensitive Achilleos et al.,
ibuprofen) from WWTP Phillip Xe lamp and UVA lamp to TiO2 P25 loading. Solar and UV-A photocatalysis appear to be 2010
(9 W Radium lamp) efficient for carbamazepine degradation.
Phenobarbital Milli-Q water High pressure Hg lamp Photocatalytic degradation rate constant of phenobarbital Cao et al., 2013
(365 nm) increased from 0.012 min1 at pH 3 to 0.027 min1 for pH 5, 7
and 9 (all three having similar values). Degradation of
phenobarbital decreased from 95% to 79% when the initial
concentration was increased from 50 mM to 100 mM.
Carbamazepine Distilled water UVA lamp (3  8 W; 365 nm) Carbamazepine was degraded up to 99% in the presence of 1.5 g/ Carabin et al.,
L TiO2 photocatalyst P90 after 90 min of treatment using a UVA 2015
lamp (365 nm).
Carbamazepine Milli-Q water Solar simulator (1000 W Xe Addition of TiO2 improved the degradation rate of Drosos et al.,
short-arc lamp) carbamazepine to 0.015 min1 compared to only 0.0005 min1 2015
during photolysis after 120 min of treatment. The presence of
natural organic matter (lignite humic acid) at low
concentrations increased the degradation of carbamazepine.
Lipid regulators
Bezafibrate Doubly distilled water Solar simulator (1500 W Bezafibrate was completely degraded within 200 min following Lambropoulou
xenon arc lamp) pseudo-first-order kinetics with rate constant, of et al., 2008
2.81  102 min1.
b-blockers
Metoprolol and Milli-Q water Solar simulator (Xe-OP lamp; Maximum removals of both compounds were achieved with Romero et al.,
propranolol 1 kW) 0.4 g/L TiO2 P25. Almost 55% of TOC and COD removal was 2011
achieved after 360 min of irradiation.
Propranolol Milli-Q water Solar simulator (Xe-OP lamp; Higher pseudo-first-order kinetic constants were obtained in De la Cruz et al.,
1 kW) and solar compound laboratory solar device (k ¼ 0.0090e0.01085 min1) than pilot 2013a
parabolic concentrators solar device (k ¼ 0.00492e0.00785 min1).
Metoprolol Deionized water Solar box (Xe lamp; 1 kW)
(continued on next page)
202 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207

Table 2 (continued )

Therapeutic class/ Water matrix Experimental conditions Results Reference

compound

TiO2 photocatalytic degradation of metoprolol followed first Romero et al.,

order kinetics, where the degradation rate constants increased 2015
from 0.0061 min1 to 0.12 min1 for 0.05 g/L and 0.4 g/L TiO2,
respectively. TiO2 concentration of 0.4 g/L also produced the
highest TOC removal (45.6%).
Others
Crotamiton (anti- Milli-Q water UV lamp (0.25e2.0 mW/cm2) The studied pH range of 3e9 did not show great influence on Fukahori et al.,
pruritic drug) the degradation rate. Pseudo-first-order rate constant increased 2012
with UV intensity.
Chlorhexidine Ultra-pure water UVA lamp (10 W) TiO2 loading of 200 mg/L removed the highest percentage of Das et al., 2014
(antimicrobial) chlorhexidine (68.2%) within 1 h of treatment at pH 10.5. TiO2
Aeroxide P25 performed slightly better than TiO2 pure anatase
in removing the chlorhexidine.
Methamphetamine Effluent from sewage UV lamp (9W; 365 nm) The apparent rate constant of 100 mg/L methamphetamine Kuo et al., 2015
(central nervous treatment plant, deionized increased from 0.12 to 2.34 min1 when the TiO2 loading was
system stimulant) water varied from 0.01 to 0.1 g/L. The degradation rate dropped when
0.4 g/L and 0.7 g/L TiO2 was used in the photocatalytic
degradation.
Methotrexate Milli-Q water UVA lamp (8W; 352 nm) The half-life of methotrexate (100 mg/L) in the TiO2 Lai et al., 2017
(antineoplastic photocatalytic treatment was 13.8 min. Addition of HCO 3
agent or (400 mg/L) in the TiO2 photocatalytic treatment reduced the
chemotherapeutic half-life to 1.8 min.
drug)
Venlafaxine Ultra-pure water UVA lamp (9W/78; 340 Degradation rate of venlafaxine increased from 0.1 min1 at the Lambropoulou
(antidepressant) e400 nm) TiO2 concentration of 0.2 g/L to 0.2 min1 at 0.6 g/L and et al., 2017
decreased when 0.8 g/L was used (pH ¼ 4.0). Complete
elimination of 2.5 mg/L venlafaxine was attained after 20 min in
the presence of 0.4 g/L TiO2.

Table 3
Characteristics comparing of TiO2 P25 to other commercial photocatalysts.

Properties TiO2 P25 Hombicat UV 100 Ti (IV) oxide (Aldrich)

Brunauer-Emmett-Teller (BET) surface area, m2/g 50 >250 190e290

Particle size, nm 21 5 15
Crystal form 80% Anatase: 20% Rutile 100% (or >99%) Anatase 100% (or >99%) Anatase

commonly used in TiO2 photocatalytic oxidation studies as shown photodegradation due to its ability to absorb light or by acting as a
in Table 3. Real water matrices such as wastewater effluents, river quencher for the photo-excited molecules, or (ii) promote photo-
or lake water and drinking (tap) water have likewise been utilized degradation by acting as a photosensitizer. The effect of NOM on the
in TiO2 photocatalytic degradation, although in general these degradation of carbamazepine was evaluated by Drosos et al.
studies are less common. The presence of radical scavengers such as (2015). This study reported that low concentrations of NOM
carbonate ions, HCO 2
3 and CO3 and natural NOM both in spiked enhanced the photocatalytic degradation of carbamazepine as a
and real wastewater samples typically impacts on the degradation result of adsorption of the NOM onto the TiO2 surface, which
efficiencies. The effect of carbonate species (HCO 
3 and CO3 ) has maintained sufficient contact for photocatalysis to occur. However,
been reported to either inhibit or enhance the degradation rate of higher concentrations of NOM were reported to impede the
pharmaceuticals. The influence of HCO 3 in pure water on the UV/ adsorption of the pharmaceuticals onto TiO2. In another study, the
TiO2 photocatalytic degradation efficiency has been studied for effect of NOM, humic acid and tannic acid, on the TiO2 photo-
methotrexate. The initial reaction rate was found to increase with catalytic degradation of carbamazepine and three of its derivatives
increasing HCO 3 concentration (20e400 mg/L) due to the reduced (carbamazepine epoxide, acridine and acridone) was reported to
self-recombination rate and longer life time of CO3 compared to


vary and to be dependent on the type and concentration of NOM


HO radicals (Lai et al., 2017). The degradation of clofibric acid in (Haroune et al., 2014). The degradation of acridine was observed to
four different environmental water matrices (tap water, river water, decrease with an increasing concentration of tannic acid, while the
mineral water and recycled wastewater) showed a >90% decrease results for the other compounds were inconclusive due to the noisy
in the degradation efficiency compared to pure water due to the data.
presence of organic matter, anions such as chlorides, sulfates and Furthermore, studies have shown that filtered or unfiltered
carbonates or in the case of recycled wastewater, due to the pres- wastewater samples influence the degradation rate of UV/TiO2
ence of alkaline, alkaline earth and heavy metals (Rioja et al., 2016). photocatalysis to different extents. For example, the photocatalytic
Аntonopoulou et al. (2016) also reported a decrease in the TiO2 degradation rate of moxifloxacin was reported to be 2 times slower
photocatalytic degradation efficiency of three transformation in unfiltered hospital wastewater than in demineralized water.
products of tramadol, namely N-desmethyl- (N-DES), N,N-bides- Despite this, a comparison of the photocatalytic degradation of
methyl (N,N-Bi-DES) and N-oxide-tramadol (N-OX-TRA), in moxifloxacin in unfiltered and filtered hospital wastewaters
secondary-treated wastewater compared to ultra-pure water, revealed no significant difference, implying that suspended par-
owing to the presence of inorganic ions and organic carbon that ticulate matter did not inhibit the degradation (Van Doorslaer et al.,
scavenged the reactive radical species. 2015). In a separate study, the TiO2 photocatalytic degradation of
The effect of NOM such as humic acid and fulvic acid on TiO2 naproxen in unfiltered river water and in the presence of phosphate
photocatalysis has been reported to either (i) inhibit the and chloride anions markedly decreased the degradation rate
 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207 203

(0.10e0.11 min1) compared to a higher degradation rate in their especially when dealing with single APIs (Jallouli et al., 2018;
absence (0.21 min1) (Kanakaraju et al., 2015). Light filtering effects Lambropoulou et al., 2017). Lai et al. (2017) attempted to compare
and competitive adsorption by NOM were held responsible for the degradation products formed during the UV/TiO2 and UV/TiO2/
these findings. HCO 3 degradation of methotrexate. As the identification of degra-
Researchers predominantly perform laboratory-scale experi- dants naturally becomes more complicated for multiple APIs,
ments with artificial UV light over pilot scale operations with studies tend to neglect this aspect as one of their objectives. A study
sunlight, as conditions are easier to control. Often, there is no direct by Kanakaraju et al. (2016) attempted to identify the main degra-
correlation between results from both protocols as shown by De la dants generated during solar TiO2 photocatalysis of a diclofenac and
Cruz et al. (2013a) for the degradation of propranolol. Factors such naproxen mixture by means of liquid chromatography mass spec-
as light intensity, available wavelengths and the photoreactor trometry (LC-MS) and Fourier transform-ion cyclotron resonance-
configuration contribute to these differences. However, pilot scale mass spectrometry (FT-ICR-MS). More studies, however are
studies are more realistic and more relevant for real high-volume needed to address the identification of degradants formed when
wastewater applications. Compound parabolic collectors (CPC) are more than one API is present in the water or wastewater.
commonly chosen for large-scale solar photocatalytic in- Existing data suggest that TiO2 photocatalysis appears to be an
vestigations, as these devices can harvest both non-concentrating excellent choice of AOP for pharmaceutical removal in pure or
and concentrating radiation (Blanco-Galvez et al., 2007). wastewater. However, limited information is available on the effi-
One important purpose of TiO2 photocatalytic treatment is the cacy of this process for the removal of pharmaceuticals in mixtures,
improvement of the biodegradability of persistent pharmaceuti- particularly in real wastewater. Various APIs belonging to different
cals. In most cases, complete degradation of the parent pharma- therapeutic groups may be present in real wastewater leading to
ceutical does not correspond directly with the mineralization rate, additive, synergistic and antagonistic effects or interactions. In
indicating the formation of more stable intermediates during the addition, as pharmaceuticals may occur in concoctions with other
degradation processes. A non-biodegradable fraction frequently pollutants such as dyes and heavy metals, future studies should
remains in the treated solution. The degree of mineralization is attempt to fill this knowledge gap. Nevertheless, simulated
usually reported as dissolved organic carbon (DOC) and total wastewater containing known mixtures of pollutants may be used
organic carbon (TOC) removal or chemical oxygen demand (COD) to investigate important aspects of TiO2 photocatalysis (e.g. toxicity,
and tends to vary based on the nature of the water matrix. Hybrid kinetics, degradation products) as interactions of multi-pollutants
methods, however, are commonly more effective in improving in real wastewater are highly complex due to the presence of
mineralization rates as well as biodegradability. For example, other substances such as anions and organic matter.
sonophotocatalysis of ibuprofen showed a higher TOC removal of
up to 92% compared to the individual process, sonolysis or TiO2 5. Conclusions and future outlook
photocatalysis, which only achieved 16% and 88%, respectively, af-
ter 3 h (Madhavan et al., 2010). This review has demonstrated the potential application of AOPs
The transformation products generated during UV/TiO2 photo- for the removal of pharmaceuticals in wastewater.
catalyzed oxidation may potentially be more toxic than the parent Current research demonstrates that pharmaceuticals are a
compound itself. Accordingly, the incorporation of a toxicity evalu- persistent type of pollutant in aquatic media with increasing
ation in pharmaceutical degradation studies is important. Toxicity environmental and health concerns. Many studies have revealed
experiments to measure antibiotic activity using bacterial strains that conventional WWTPs are the main entry point of APIs to
such as Escherichia coli and Enterococcus faecalis, inhibition test us- surface waters in trace quantities. The role of an abiotic process
ing bacteria such as Vibrio fischeri and bioassay tests to determine involving biological degradation remains unclear due to contra-
EC50 or LC50 have been reported. The presence of toxic by-products dicting evidence. Various factors dictate the behaviour of APIs to-
during or after the treatment has been generally reported as the wards biological degradation. Gathered evidence on the effects of
main factor contributing to toxicity (Calza et al., 2006; Me ndez- pharmaceuticals' presence and detection signify the seriousness of
Arriaga et al., 2008a). In most cases, toxicity was found to be high these pollutants. More risk assessment studies investigating the
during the initial period of the treatment and to decrease towards ecological effects of pharmaceuticals and their metabolites should
the end, demonstrating the potential detoxification ability of pho- be performed. To address the limitations of conventional WWTPs,
tocatalysis. Recent research showed that by-products generated AOPs should be considered as alternatives or add-ons as they often
during the UV/TiO2 treatment of methotrexate in the presence of offer better removal efficiencies.
HCO 3 anions increased toxicity for 12 h of treatment, while no Researchers have applied different AOPs in order to degrade or
toxicity was observed in the absence of HCO 3 anion (Lai et al., 2017). remove pharmaceuticals in water or wastewater. Typically, most
Likewise, it has been reported that a photoproduct of diclofenac, i.e. AOP studies on pharmaceuticals deal with (i) the degradation ki-
8-chlorocarbazole-1-yl- ethanoic acid, displayed higher toxicity netics by investigating the effect of operational parameters, (ii)
than the parent compound (García-Araya et al., 2010). Therefore, mineralization measurements using indicators like TOC, DOC or
attention must be paid to ensure that there are no more toxic or COD, (iii) toxicity studies and (iv) the profiling or identification of
more persistent products formed compared to the parent pharma- degradants. Although it is evident from most of the reviewed
ceutical being degraded. Emphasis on the identification of trans- studies that AOPs are efficient in the degradation of pharmaceuti-
formation products has been lacking in the literature, especially cals, the identification of transformation products and toxicity
when real wastewater samples were involved. A few possible rea- levels are equally crucial as these products can be more biologically
sons for this neglect are: (i) difficulties in separating and identifying active or toxic than their parent compounds, thus imposing even
the often large number of transformation products formed, (ii) lack greater hazards to the environment. Although synthetic waste-
of or non-existent analytical standards to determine the identity of water samples have generally been used for degradation studies,
these transformation products and (iii) requirements for more than more studies are being carried out using real wastewater samples.
one analytical technique or sample preparation technique due to As a result, more useful information is becoming available for the
their diverse physicochemical properties (Agüera et al., 2005; Fatta- application of AOP in real industrial settings. As the matrix of real
Kassinos et al., 2011b). Despite this, transformation products and wastewater sample is complex due to the presence of organic and
degradation pathways have been proposed in various studies, inorganic substances and due to variations of the wastewater
204 D. Kanakaraju et al. / Journal of Environmental Management 219 (2018) 189e207

characteristics, a reliable AOP protocol needs to be chosen to ensure (AOP) for water purification and recovery. Catal. Today. 53, 51e59.
Andreozzi, R., Marotta, R., Paxeus, N., 2003. Pharmaceuticals in STP effluents and
its effectiveness. Moreover, the complex nature of wastewater
their solar photodegradation in aquatic environment. Chemosphere 50,
samples makes the identification of degradation products chal- 1319e1330.
lenging and difficult. Besides single AOP techniques, hybrid or Andreozzi, R., Canterino, M., Marotta, R., Paxeus, N., 2005. Antibiotic removal from
combined techniques are also becoming popular to achieve high wastewaters: the ozonation of amoxicillin. J. Hazard. Mater. 122, 243e250.
Antonopoulou, M., Hela, D., Konstantinou, I., 2016. Photocatalytic degradation ki-
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tropic pharmaceuticals in an urban river in a subcatchment of the Yodo River
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Basha, S., Barr, C., Keane, D., Nolan, K., Morrissey, A., Oelgemo €ller, M., Tobin, J.M.,
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