Journal of Environmental Management 262 (2020) 110347

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Journal of Environmental Management

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

Research article

Degradation of metformin in water by TiO2–ZrO2 photocatalysis

Caroline F. Carbuloni a, Jaqueline E. Savoia a, Jaqueline S.P. Santos a, Cíntia A.A. Pereira b,
Rubiane G. Marques a, Valquíria A.S. Ribeiro a, Ana M. Ferrari a, *
a
Federal University of Technology – Parana, Rua Marcilio Dias, 635, 86812-460, Apucarana, Brazil
b
State University of Maringa, Av Colombo, 5790, 87020-900, Maringa, Brazil

A R T I C L E I N F O A B S T R A C T

Keywords: The increasing use of pharmaceutical products also increases their release in aquatic environment. These con­
Photocatalysis taminants are considered emerging pollutants, and induce adverse ecological and human health effects. The
Photodegradation antidiabetic metformin is one example that has been detected in the aquatic environment at unusual concen­
TiO2
trations. This fact indicates that conventional wastewater treatment is inefficient on eliminating this compound.
ZrO2
Metformin
Here we show that metformin can be effectively removed from water by photocatalysis. We found the optimised
Toxicity conditions for pH and concentration of catalyst on the photocatalytic process. TiO2 and TiO2–ZrO2 were suc­
cessful in oxidising metformin under UV radiation following a pseudo-first order kinetics. Intermediates of
metformin photodegradation appeared after photocatalytic treatment. Toxicity analysis showed that the
degradation products are non-toxic to Lactuca sativa seeds.

1. Introduction Recent reports proved that residual metformin acts as an endocrine

disruptor at environmentally relevant concentrations. Exposition to a
The development of anthropic activities has been causing several concentration of metformin found in wastewater effluent (40 mg L 1)
environmental problems. Emerging pollutants in aquatic environments caused intersex and reduced fecundity on fishes (Niemuth and Klaper,
has increased excessively and its environmental or public health risks 2015). Some studies report that residues of metformin and its
have not been yet established (Naidu et al., 2016). Among these con­ by-product, guanylurea (C2H6N4O), usually occurs in drinking water
taminants, pharmaceuticals for human and veterinary use have become (Quint~ ao et al., 2016; Baken, 2014; Scheurer et al., 2012; Trautwein and
an environmental issue. The predominant migration routes of these Kümmerer, 2011). This occurs due to hydrophilicity and aqueous
compounds to the environment are excretions through urine and faeces mobility, biorecalcitrance, and usual occurrence as complex cocktails
(Daughton and Ternes, 1999). Insufficient removal by conventional (Vasquez et al., 2014; Beyer and Meador, 2011). Additionally, the
water/wastewater treatment plants has resulted in the release of deficiency of water and wastewater treatment plants is the main
emerging pollutants in the water cycle, from wastewater to drinking responsible for releasing pharmaceuticals on water. In this sense,
water. advanced techniques are strongly needed.
Metformin, or N,N-dimethylbiguanide (C4H11N5), is the most anti- The oxidation of metformin induced by direct photolysis, photo­
hyperglycemic agent used in the management of non-insulin depen­ catalysis (TiO2/UVC) and ozonation was recently studied by Quint~ ao
dent diabetes mellitus (NIDDM) or type II diabetes. After administration, et al. (2016). The mineralization rates varied and there was accumula­
metformin is not metabolised by the human body and is totally excreted. tion of degradation by-products in all experiments. Mezenner and
In the last few years, some studies have investigated the presence of Hamadi (2012) investigated the photodegradation of metformin at room
metformin on sewage (Kosma et al., 2015), hospital wastewater (Santos temperature with TiO2/UVA system. Optimised conditions where pH 8.0
et al., 2013), drinking water/drinking water treatment plant (Houtman and 0.5 g L 1 of TiO2 for 0.5 mg L 1 of initial metformin concentration.
et al., 2014; Scheurer et al., 2012) and surface water (Blair et al., 2013). Recently, Chinnaiyan et al. (2019) investigated the photocatalytic
Concentrations of 349 ng L 1 on surface water (Trautwein et al., 2014), degradation of synthetic hospital wastewater containing amoxicillin and
and 47 μg L 1 (Blair et al., 2013) and 10 μg L 1 (Scheurer et al., 2012) on metformin under UV-A radiation applying TiO2, and found that the
treated sewage have been reported. maximum removal occurred when the pH was 7.6, TiO2 dosage was 0.5

* Corresponding author.
E-mail addresses: ana_eq@hotmail.com, analima@utfpr.edu.br (A.M. Ferrari).

https://doi.org/10.1016/j.jenvman.2020.110347
Received 7 November 2019; Received in revised form 20 January 2020; Accepted 24 February 2020
Available online 29 February 2020
0301-4797/© 2020 Elsevier Ltd. All rights reserved.
C.F. Carbuloni et al. Journal of Environmental Management 262 (2020) 110347

g L 1, and reaction time was 150 min for initial concentration of con­ a JEM-1400 (JEOL) microscope, applying 120 kV acceleration voltage.
taminants at 10 mg L 1. Zero Point of Charge has been determined according to Al-Harah­
Titanium dioxide (TiO2) is widely used as photocatalyst, due to its sheh et al. (2009). 1.0 g of catalyst was added to 30 mL of 0.1 M po­
high chemical stability and efficiency, availability and low cost. How­ tassium nitrate solution. The initial pH was adjusted to 2, 4, 6, 8, 10 and
ever, its photocatalytic activity is still unsatisfactory for practical ap­ 12 by the addition of drops of nitric acid (HNO3) or dilute potassium
plications due to the high recombination rate of photogenerated hydroxide (KOH). The suspension was stirred for 24 h and the final pH
electron-hole pairs. The n-type semiconductor ZrO2 has physico- was then measured.
chemical properties similar to TiO2, and is thus expected to be effi­
cient for application in photocatalysis when coupled with TiO2 (Pirzada 2.2. Photocatalytic tests
et al., 2015). ZrO2 is commonly applied as photocatalytic material due to
its chemical inertness, excellent thermal stability, nontoxicity, The photoactivities of the prepared powders were measured in the
re-usability and low cost (Tian et al., 2019). The increase in photo­ photodegradation of metformin (MTF) 10 mg L 1 aqueous solution. The
catalytic activity of TiO2–ZrO2 composites is commonly associated with photocatalytic tests were carried out in a 500 mL self-designed inox
changes in their textural and structural properties, such as high surface reactor (Fig. 1). The temperature of the reaction was maintained at 25.0
area, small particle size, high anatase phase content and energy band � 0.5 � C by using a cooling jacket. A 125-W mercury lamp without bulb
gap variation (Qu et al., 2014). was used as UV source and inserted into the reactor chamber protected
To the best of our known, the scenario for degradation of metformin by a quartz tube. Metformin concentration was measured by UV–Vis
by advanced oxidation processes, attempting to photocatalysis, is still spectroscopy at 233 nm after separation from the catalyst by a 45 μm
understudied. Therefore, our study aims to investigate metformin membrane. Spectroscopy quantification method have been established
degradation induced by photocatalysis with TiO2–ZrO2 composites after in-depth literature evaluation (Nezar and Leoufi, 2018; Patel et al.,
under UV radiation. 2017; Mezenner and Hamadi, 2012; Nyola and Jeyabalan, 2012; Mishra
et al., 2011, Arayne et al., 2009). TiO2 P25 (Evonik) was applied by
2. Methods means of comparison. All the experiments were performed in triplicate.

2.1. Synthesis of catalysts and characterisation 2.3. Phytotoxicity tests

Photocatalysts were synthesized by the sol-gel method, where 0.027 Lactuca sativa seeds were applied as phytotoxicity bioindicator. The
mol of titanium IV n-butoxide precursor was diluted in 100 mL of ab­ working solutions consisted of the raw MTF synthetic wastewater (10
solute ethanol with magnetic stirring for 1 h. Distilled water (12 mL) mg L 1) and the sample after treatment at optimised conditions (final
were added dropwise for the formation of the gel. The gel was then MTF concentration ¼ 4.7 mg L 1). Petri dishes of 9 mm were lined with
stirred for 24 h, dried and finally calcined at 450 � C during 4 h. filter paper where the sample unit containing 17 lettuce seeds (Lactuca
The same procedure was used for 100% zirconium oxide, where only sativa) with 99.9% of germination index and 7 mL of the sample to be
the precursor was replaced by zirconium IV (97%). The mixed oxides of tested. 7 mL of distilled water was applied as positive control and 7 mL
zirconium and titanium (5 and 95%) were synthesized following the of NaCl solution 1 mol L 1 was applied as negative control. The plates
same procedure, modifying only the percentage of precursors. were placed in an incubator at a temperature of 22 � C for 120 h. Seed
The photocatalysts were characterised by BET textural analysis, zero germination and root length were calculated according to the following
point of charge (pHZPC), transmission electron microscopy (TEM) and x- equations: Relative root elongation ¼ [(Mean root length)/(Mean root
ray diffraction (XRD). XRD analysis were performed in a Rigaku model length in control)] � 100; Relative seed germination ¼ (Seeds germi­
Mini Flex 600 (PDXL software) equipment and N2 adsorption-desorption nated/Seeds germinated in control � 100).
isotherms were obtained from a Nova 1000 Series QuantaChrome
equipment. Transmission electron microscopy images were obtained on

Fig. 1. Scheme of the photoreactor.

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C.F. Carbuloni et al. Journal of Environmental Management 262 (2020) 110347

3. Results and discussion 3.2. Photocatalytic tests

3.1. Catalysts characteristics 3.2.1. Exploratory tests

Photodegradation and photolysis where performed with a 10 mg L 1
The synthesized catalysts were analysed by X-ray diffraction (XRD), metformin solution at the natural solution pH (5.4). Reactions were
zero point of charge (pHZPC), transmission electron microscopy (TEM) performed with the four synthesized catalysts and commercial P25
and BET method. The XRD analysis provided information on the crys­ catalyst. Starting value of catalyst concentration was 0.5 g L 1. The
talline structure and the phases present in the materials, the diffracto­ photodegradation tests performed with and without catalysts at
grams obtained from the photocatalysts used in the photocatalytic tests different time intervals are shown in Fig. 4. We can observe that the
are shown in Fig. 2. more active catalysts are TiO2 and TiO2–ZrO2 (95–5), degrading almost
TiO2 is present in the anatase phase and ZrO2 in tetragonal and 50% of the initial MET concentration in 30 min. Quint~ ao et al., (2016)
monoclinic phases. The presence of the anatase phase is fundamental, reported a removal efficiency of 31% of MTF (10 mg L 1) after 30 min of
because it is the most photoactive form of TiO2, which facilitates the UV-C irradiation in presence of TiO2 with no pH adjustment. Chinnaiyan
formation of the electron-hole pairs during the photocatalytic process. et al. (2019) optimised the photodegradation of MTF and amoxicillin in
Similar results were found by Zurlini et al. (2009). a synthetic wastewater and reached 92% of MTF (10 mg L 1) removal at
The BET method provided information on the textural analysis of the pH ¼ 7.6, TiO2 dosage of 0.5 mg L 1 and reaction time of 150 min.
materials. TiO2 presented a specific surface area of 85 m2 g 1 and pore The photocatalytic reactions were adjusted to a pseudo-first order
volume of 134 cm3 g 1, higher BET area and pore volume than ZrO2 kinetics and the kinetics constants are presented on Table 1. Mezenner
(BET area of 79.3 m2 g 1 and pore volume of 103 cm3 g 1). TiO2/ZrO2 and Hamadi (2012) found a kapp of 0.0076 min 1 for degradation of a 15
mixed oxides had larger specific surface area and pore volume than the mg L 1 metformin solution with a UV lamp applying TiO2 (0.5 g L 1).
pure oxides, thus showing that is ZrO2 was not impregnated on TiO2 The increase on drug concentration decreased the kinetic constant. In
internal surface. The larger surface area for the combined oxide suggests our work, the highest kapp values were found for TiO2 and TiO2– ZrO2
that an intermediate oxide of ZrxTiyO(1-x-y) was obtained with an (95–5). This occurred because excess ZrO2 doping probably reduced the
improvement in surface area and pore volume. It was also noted that all mobility of the charge carriers on TiO2–ZrO2 (5–95), increasing the
catalysts had a mean pore diameter of mesoporous structure. All iso­ surface recombination rate. Based on the results obtained, both TiO2 e
therms were Type IV (not shown) with monomodal pore diameter size. A TiO2–ZrO2 (95–5) catalysts were chosen for the optimisation of the re­
uniform sphere was associated with the distribution of pore size, since a action conditions.
H1 type hysteresis was observed (Sing et al., 1985).
The values of pHZPC varied from 6,0 to 6,5 for all the powders. 3.2.2. Optimisation of reaction parameters
Catalytic surface will get positively charged if metformin solution pH < Analysing the catalyst dosage is essential, since the speed of the
pHZPC and negatively charged if metformin solution pH > pHZPC. photocatalytic reaction is proportional to its quantity, when used in low
Transmission electron microscopy (TEM) images of TiO2, ZrO2, and concentrations. However, an excess of catalyst in the reaction medium
TiO2–ZrO2 (95–5) are shown in Fig. 3(a and b, c), respectively. Fig. 3 (a) can cause scattering of light and formation of clusters, reducing the
illustrates that titanium dioxide has homogeneous distribution, having a available surface area and the efficiency of the process.
spherical structure with porous surface. According to Tonejc et al. According to Mezenner and Hamadi (2012) the best concentration
(2001), anatase TiO2 has smaller grains compared to the rutile, with for TiO2 (P25) was 0.5 g L 1. In this work, concentrations of 1.0 g L 1
critical grain size between 10 and 20 nm. The sizes obtained in this and 1.5 g L 1 were also studied. Metformin photodegradation tests at
synthesis were smaller than 50 nm, corroborating with the X-ray different concentrations of TiO2 are shown in Fig. 5. It can be noted that
diffraction results. the best dosage is 1.0 g L 1, since it is better than 0.5 g L 1, and 1.5 g L 1
Fig. 3 (b) shows that zirconium dioxide is composed of peanut- of catalyst have not shown any significant improvement on the photo­
shaped smooth surface grains smaller than 100 nm. Zhang, 2008 used degradation after 180 in of reaction.
higher temperatures, obtaining larger grains, concluding that as tem­ The evaluation of metformin photodegradation at different pH
perature increases, grain size increases. TiO2–ZrO2 (95–5) presented values and concentration of 1.0 g.L 1 of TiO2 is shown in Fig. 6. The pH
nanometric grains and higher porosity Fig. 3 (c). ¼ 8 was chosen as the one with the best activity. Fig. 7 presents the
distribution of the different species of metformin as a function of pH. At
pH ¼ 8 the molecule is protonated in two amino groups, explaining why
this drug has a strong basic character. Additionally, at this pH, the
catalyst surface is negatively charged (pH > pHZPC), thus favouring
adsorption.
The optimised conditions chosen for TiO2 and TiO2–ZrO2 (95–5)
were adopted at 1.0 g L 1 of catalyst and pH ¼ 8. The results obtained
after 30 min of UV radiation are shown in Fig. 8. The activity of both
catalysts throughout the photocatalytic reaction was similar and in the
first few minutes under UV radiation the analyte was significantly
degraded. We can note that the addition of ZrO2 did not provide any
improvement on the photocatalytic activity of TiO2. This result is
different from the reported by Li et al. (2015), where TiO2 modified with
2.0, 4.1, 6.9 and 9.8% of ZrO2 was better than pure TiO2. This different
behaviour occurred because of the incorporation of ZrO2 in the TiO2
matrix, which reduced recombination rate.
It is well known that advanced oxidation process applied to con­
taminants degradation can generate toxic intermediates and it must be
investigated. Fig. 9 expresses the UV–Visible spectrum of the metformin
under optimised conditions for TiO2. Two intermediates appeared dur­
ing the photocatalytic reaction, which were not eliminated after 180 min
Fig. 2. Diffractogram of the synthesized catalysts. of UV radiation. At 233 nm, the differential absorbance is decreasing due

3
C.F. Carbuloni et al. Journal of Environmental Management 262 (2020) 110347

Fig. 3. TEM images of (a) TiO2, (b) ZrO2 and (c) TiO2–ZrO2 (95–5).

to consumption of metformin, while it increases at 207 and 258 nm due degradation by-products were non-toxic. Methylbiguanide was also re­
to the formation of oxidation products. ported as the as the major product of the one-electron oxidation of
According to Collin et al. (2004), 258 nm is a characteristic wave­ metformin in aqueous solution by Trouillas et al. (2013).
length of aromatic structure and identified 4-amino-2-imino-1-methyl-1, Additionally, it is already known that a transformation product of
2-dihydro-1,3,5-triazine (4,2,1-AIMT) as one oxidation product of metformin is guanylurea (C2H6N4O), commonly identified after
metformin, which might be considered as the compound that absorbs at biodegradation (Quinta ~o et al., 2016; Oosterhuis et al., 2013; Scheurer
this wavelength. et al., 2012). Furthermore, toxicity analysis was performed with raw and
Khouri et al. (2004) observed the same behaviour for the oxidation of treated solution.
metformin by gama radiolysis in water. Four end-products of OH�-in­
duced oxidation of metformin have been identified: 1-methylbiguanide 3.2.3. Toxicity tests
(MBG), a dimer of metformin (diMTF), a hydroperoxide of metformin Samples after photodegradation with TiO2 (1.0 g L 1) and pH ¼ 8
(MTFOOH) and 4,2,1-AIMT. were chosen to evaluate the cytotoxicity against the bioindicator Lactuca
Quinta~o et al. (2016) also identified MBG (C3H9N5) and 4,2,1-AIMT sativa. A 100% relative germination was achieved for the treated sam­
(C4H7N5) as photodegradation intermediates of metformin under UV ples, while in the untreated sample de relative germination was 94%.
radiation with TiO2. After toxicity tests, the authors concluded that the Germinated seeds on treated sample can be observed in Fig. 10. The

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C.F. Carbuloni et al. Journal of Environmental Management 262 (2020) 110347

1.0 1.0
pH 5.4
0.9 pH 8.0
0.8 pH 10.0
0.8

0.6 0.7
C/Co

C/Co
0.6 Dark
0.4
Dark Photolysis
0.5
P25
TiO2
0.4
0.2 TiO2/ZrO2 (95-5)
TiO2/ZrO2 (5-95) 0.3
ZrO2
0.0 0.2
-20 -10 0 10 20 30 40 50 60 -20 -10 0 10 20 30 40 50 60
Time (min) Time (min)
1
Fig. 4. Photodegradation of metformin (10 mg L ) as a function of time under Fig. 6. Photodegradation of metformin (10 mg.L 1) over TiO2 at different pH.
UV radiation.

Table 1
Pseudo-first order kinetics constant (kapp) for the photodegradation of metfor­
min (10 mg L 1) under UV radiation.
1 1
Catalyst (0.5 g.L ) kapp (min ) R2

Photolysis 0.0050 0.9847

P25 0.0056 0.8503
TiO2 0.0082 0.8800
5% ZrO2–TiO2 0.0099 0.8047
5% TiO2–ZrO2 0.0055 0.9651
ZrO2 0.0071 0.9767

1.0

0.9

0.8

0.7

0.6
Fig. 7. Different species of metformin on pH range of 0–14. Source: Scheurer
et al. (2009).
C/Co

0.5

0.4 Dark
0.3
-1
0.2 0.5 g L
-1
1.0 g L
0.1 -1
1.5 g L
0.0
-20 0 20 40 60 80 100 120 140 160 180
Time (min)

Fig. 5. Photodegradation of metformin (10 mg L 1) at different concentrations

of TiO2.

relative germination and relative root elongation were calculated and

are present on Table 2.
The value for the relative root growth for the treated sample was
higher than 100%. It can be explained by the fact that the roots of the
sample grew more than the roots of the control. The highest growth of
the roots in the sample possibly occurred due to the formation of
nitrogenous molecules during the degradation of metformin, acting as a
source of nutrients for the seeds. However, no formation of ammonia has 1
Fig. 8. Photodegradation of metformin with 1.0 g L of catalyst and pH ¼ 8.
been identified on the photodegradation products.

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C.F. Carbuloni et al. Journal of Environmental Management 262 (2020) 110347

4. Conclusion

TiO2–ZrO2 catalysts were synthesized and characterised and the

performance on the photocatalysis of metformin were investigated. The
photodegradation reactions of the metformin solution under UV radia­
tion were adjusted to the pseudo-first order kinetics and highest kinetics
constants were 8.2 � 10 3, 9.9 � 10 3, for catalysts TiO2 and TiO2–ZrO2
(95–5), respectively. After the optimisation of the reaction conditions,
TiO2 and TiO2–ZrO2 (95–5), were chosen to have their photocatalytic
activities evaluated. Toxicity tests were performed for the treated
effluent (4 mg L 1 residual metformin) after photodegradation with
TiO2 and the results showed that there was no impediment on lettuce
seed germination and root growth.

Declaration of competing interest

The authors declare that they have no known competing financial

interests or personal relationships that could have appeared to influence
the work reported in this paper.

Fig. 9. UV–Visible spectrum of the metformin under optimised conditions CRediT authorship contribution statement
for TiO2.

Caroline F. Carbuloni: Investigation, Writing - original draft.

Jaqueline E. Savoia: Investigation, Writing - original draft. Jaqueline
S.P. Santos: Investigation, Writing - original draft. Cíntia A.A. Pereira:
Methodology, Writing - original draft. Rubiane G. Marques: Concep­
tualization, Methodology, Writing - review & editing. Valquíria A.S.
Ribeiro: Writing - review & editing. Ana M. Ferrari: Supervision,
Writing - review & editing.

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