1. 1
PHOTOCATALYTIC OXIDATION OF PHARMACEUTICALS IN
AQUEOUS SUSPENSION OF TiO2
Mehdi Aissani Abdelkader and Ahmad Muzafar Azman
Department of Chemical Engineering, Loughborough University, Loughborough, Leics. LE11 3TU, UK.
A R T I C L E I N F O
Article history:
Completed 14 March 2014
Keywords:
Photocatalysis
Pharmaceuticals
Titanium dioxide
Reactive Oxygen Species
A B S T R A C T
The photocatalytic degradation of four pharmaceuticals com-
pounds has been studied in equimolar solutions; TiO2 has been
used as a photo catalyst. To assess the effectiveness of the photo
catalyst, scavengers have been added to the mixture. The intention
of using different types of scavengers is to see the contribution of a
series of reactive oxygen species (ROS) on the degradation of caf-
feine, diclofenac, trimethoprim and hydrochlorothiazide. It has been
found that the degradation of caffeine was affected by both hy-
droxyl and singlet oxygen radicals. The degradation of diclofenac
was significantly affected by photogenerated holes and hydroxyl
radicals. Singlet oxygen was the main ROS involved in the degra-
dation of hydrochlorothiazide and trimethoprim.
1. INTRODUCTION
Pharmaceuticals constitute a large group of me-
dicinal human and veterinary compounds with a
high consumption world-wide. As pharmaceuticals
are designed to increase their potency, bioavaila-
bility and degradation resistance, they became
persistent organic compounds in the environment
[1]. Pharmaceuticals compounds are absorbed by
humans or animals to meet their therapeutic func-
tions. Then, they are metabolized to other organic
compounds. A significant fraction of any medica-
ment is often excreted in an unmetabolized form
or as active metabolites via urine or faeces.
Therefore most of the wastewater streams contain
a great variety of those organic chemical com-
pounds [2]. The presence of pharmaceuticals in
water bodies has become a major issue nowa-
days especially in suburban areas where water
pollution is more likely to be severe.
According to MD Hernando [3], the existence
of pharmaceutical residues such as antibiotic in
water can induce toxic effect and cause re-
sistance in natural bacterial populations even at
low level concentrations of antibiotic (ng/L to µg/L).
Since the beginning of the nineties of the past
century, identification of pharmaceutical com-
pounds in urban wastewater and, even, in surface
and drinking water and the study of technologies
for their removal is one of the main research lines
of water treatment [4]. Removing these pharma-
ceutical residues can be difficult and requires ad-
vanced oxidation processes such as photolysis,
heterogeneous photocatalysis, wet air oxidation
and many more [5].
1.1 Photocatalytic Degradation of Pharmaceu-
ticals
According to Ranjit and Zia [6], degradation of any
drug substance usually involves processes such
as hydrolysis, oxidation, heat and photolysis. Pho-
tocatalytic degradation process has become more
important today because of its reliability and effi-
ciency of removing pollutants in aqueous suspen-
sions. An alternative method of removing phar-
maceuticals in aqueous suspensions over com-
peting processes is degradation of pharmaceuti-
cals under visible and UV light irradiation with the
aid of photocatalysts.
1.2 Photocatalysts
Bhatkhande et al [7] defined photocatalysts as
solids that promote photo reactions with the pres-
ence of light and not consumed in the overall re-
action. They also described the characteristics of
good photocatalysts; (i) photoactive, (ii) able to
utilize visible and/or near UV light, (iii) biologically
and chemically inert, (iv) photostable, (v) inexpen-
sive and (vi) non-toxic [6]. Titanium dioxide, TiO2
is commonly used today as a photocatalyst in
photoreactions due to its chemical stability, low
cost, high refractive index and low level of toxicity
[7]. The photocatalytic performance of TiO2 de-
pends not only on its bulk energy band structure
but, to a large extent, on its surface properties [8].
When TiO2 absorbs UV light, electrons gain
energy and move from valence band to the con-
2. 2
duction band as shown in Figure 1, leaving posi-
tively charged holes in the valence band. Holes
(h
+
) and electrons (e
-
) can recombine or can react
with molecules on the TiO2 surface. Holes react
with H2O and OH
-
to generate hydroxyl radicals,
•OH, while electrons react with O2 to form super-
oxide radicals, O2
-•
[9]. The following reactions
show how a series of reactive oxygen species
(ROS) are formed during the photoreaction. The
production of these ROS could lead to oxidative
degradation of chemical compounds in an aque-
ous suspension during photocatalysis [5]. The
starting equation for ROS generation of electrons
and h
+
as shown below.
( ) → ( ) (1)
→ (2)
→ (3)
→ (4)
→ (5)
→ (6)
Figure 1: Schematic diagram of an irradiated TiO2
semiconductor particle with photo-chemical and photo-
physical process [10].
When the TiO2 photocatalyst is illuminated, the
holes react with the adsorbed water, H2Oads or
•OH which are generally accepted to be responsi-
ble for initiating the oxidation pathway. On the
other hand, the electrons are responsible for initi-
ating photo reduction reactions [11].
1.3 Scavengers
Studies have shown that there are several im-
portant factors affecting the degradation mecha-
nisms. For example, Stapleton et al [13] conduct-
ed a study of the effect of pH, radical scavenger
tert-butyl alcohol and inorganic ions on the degra-
dation of pyridine and other pyridine derivatives.
Chun Zhao et al, studied the effect of different
types of scavengers (tert-butyl alcohol (TBA), so-
dium azide (NaN3) and potassium iodide (KI) solu-
tion) and the role of pH on the photochemical deg-
radation of oxyteracycline in aqueous solutions
under visible and solar light [5].
Scavengers are used in photocatalytic reac-
tions to probe the formation of O2
-•
and singlet
oxygen radicals,
1
O2 which are generated on sur-
faces of catalysts. Konaka et al [12] conducted a
research to study the generation of both O2
-•
and
1
O2 from irradiation of TiO2. There are many dif-
ferent types of scavengers that are being used
today. Some scavengers may attack only one
type of ROS while others may scavenge multiple
ROSs. According to P. Raja et al [15], NaN3 is
widely used to quench
1
O2. TBA is considered to
be an effective •OH quencher [5]. KI on the other
hand is an effective scavenger for both •OH and
h
+
[13].
2. MATERIALS AND METHODS
2.1 Materials
Caffeine, trimethoprim (≥98%), hydrochlorothia-
zide, diclofenac sodium salt and TBA (≥99.5%)
were obtained from Sigma Aldrich. TiO2 was pur-
chased from Degussa P25. Dimethyl sulfoxide
(≥99.7%) was acquired from Acroseal. The other
reagents used were all of analytical grade. All
aqueous solutions were prepared using ultrapure
water. The resistivity of the ultrapure water used
was measured 15 MΩcm at 20 ºC.
2.2 Photochemical reactor
Figure 2: Front view of the photochemical reactor.
The photochemical reactor was set up as shown
in Figure 2. As a safety precaution, Pyrex glass
reactor was used in this experiment to avoid UV
radiation from escaping into the air. A UVC lamp
(8W Philips TUV-8W-G8-TS) with primary emis-
sion at 254 nm and 40.1 mW/cm
2
was fitted into a
quartz tube and was placed inside the reactor.
The length of the UV lamp was 298 mm. The
height of the reactor was measured to be 43.7 cm.
Liquid was pumped using a MasterFlex® peristal-
3. 3
tic pump from 2 L vessel to the bottom of the re-
actor and out to the side which goes back to the 2
L vessel.
2.3 Preparation of pharmaceutical solution
Pharmaceutical solutions of caffeine, trimethoprim,
hydrochlorothiazide and diclofenac were prepared
separately in a 2 L volumetric flask. The concen-
tration of each pharmaceutical in the 2 L volumet-
ric flask was as follow: 20 mg/L of diclofenac so-
dium, 6.10 mg/L of caffeine, 18.24 mg/L of trime-
thoprim and 18.72 mg/L of hydrochlorothiazide.
The stock solutions were transferred into 1 L
glass bottles and stored in a fridge when not in
use. For each experiment, a 2 L equimolar solu-
tion was made from the stock solutions.
2.4 Preparation of scavenger solutions
Each scavenger solution was prepared in 100 ml
at 1 M concentration. In order to prepare KI solu-
tion, 16.6 g of solid KI was dissolved into 100 mL
ultrapure water. Preparation of NaN3 solution was
done by dissolving 6.5 g of NaN3 salt into 100 mL
ultrapure water. Lastly, 9.5 mL or 7.412 g of TBA
was measured and diluted with 100 mL ultrapure
water.
2.5 Experimental procedure
The experiment comprised of two parts. The first
part of the experiment was carried out accordingly:
0.4 g/L of TiO2 was added into the pharmaceutical
solution. 20 mL of 1 M KI solution was added into
the solution and the solution was stirred using a
magnetic stirrer for 30 minutes in the absence of
UV radiation. The pH of the pharmaceutical solu-
tion was adjusted to 7.5 using 0.5 M sodium hy-
droxide, NaOH. The pump (500 mL/min) was then
switched on to allow circulation of the pharmaceu-
tical solution for 30 minutes. A sample was taken
out from the solution to measure the initial con-
centration of each pharmaceutical. The UVC lamp
was then switched on and samples were taken at
5, 10, 20, 30, 60, 90 and 120 minutes using a sy-
ringe. In order to separate TiO2, the samples were
filtered using 0.22 µm Millex® filters and the con-
centration of each sample was measured. The
experiment was repeated using different scaven-
gers; 10 mL of 1 M NaN3 solution and 20 mL of 1
M TBA solution.
The steps in the first part were repeated for the
second part of the experiment for the control run
(no scavengers added). The initial pH of the
pharmaceutical solution was kept constant for
each run.
2.6 Analytical procedure
All the samples taken out from the solution were
analysed in a HPLC-DAD (Hewlett Packard Ag-
ilent series 1100) with a 5 µm 250 4.6 mm Phe-
nomenex C-18 column to separate the pharma-
ceuticals and measure the concentration of each
pharmaceutical in order to observe their degrada-
tion. The mobile phase was a 10:90 acetoni-
trile:pH 3.5 ultrapure water. The elution was deliv-
ered at rate of 1 mL/min with detection wave-
length of 273 nm. The injection volume of the
samples was 10 µL.
3. RESULTS AND DISCUSSION
3.1 Effect of radical scavengers on the degra-
dation rate of pharmaceuticals
The photocatalytic degradation of the four phar-
maceuticals is shown in Figures 5 and 6. Figure
5 shows that caffeine (CAF) and trimethoprim
(TMP) were not degraded efficiently in all experi-
ments. A possible reason would be that, the pho-
tocatalytic activity of the TiO2 Degussa P25 used
was not high enough for the caffeine to be de-
graded in the period of time the experiment was
conducted. Using a modified TiO2 such as Au/TiO2
and Ag/TiO2 which have higher photocatalytic ac-
tivity may aid the degradation of caffeine. The
metals deposited on the surfaces of the catalyst
act as sites for capturing electrons and disrupting
the electron-hole (e
-
, h
+
) recombination which oc-
curs during photo excitation step [14]. This allows
the formation of •OH via reaction shown in equa-
tion 2.
3.1.1 Photocatalytic degradation of Caffeine
Caffeine is an antagonist of adenosine, thus its
chemistry is dominated by radical adduct for-
mation in the presence of oxidative radicals such
as •OH [15]. L.E. Jacobs et al [16] suggested that
56% of the degradation of caffeine is via addition
of •OH to C8 which leads to the formation of
1,3,7-trimethyluric acid. Since 56% of the overall
degradation is via •OH, KI and TBA scavengers
would decrease the degradation rate of caffeine.
As opposed to the pharmaceuticals used in the
experiment, caffeine especially cannot be de-
graded efficiently without the existence of photo-
catalyst [15]. However, even with the presence of
TiO2 Degussa P25 catalyst the degradation rate
of caffeine was found to be very slow. As a result,
adding scavengers to examine the possible ef-
fects of the controlling mechanisms was difficult to
evaluate, however Figure 6(h) shows that the
effect of adding any of the three scavengers re-
sults in slower rate of degradation of caffeine.
This implies that the possible active species af-
fecting the degradation of caffeine are •OH and
1
O2.
4. 4
3.1.2 Photocatalytic degradation of Hydrochlo-
rothiazide
The degradation rate of hydrochlorothiazide was
significantly supressed with the presence of NaN3
as the
1
O2 scavenger. The addition of TBA slightly
supressed the degradation rate of hydrochlorothi-
azide. This suggests that •OH provides less im-
pact on the degradation of hydrochlorothiazide
compared to
1
O2, however the degradation rate of
hydrochlorothiazide was faster with the presence
of KI. Since KI is a good quencher of h
+
, the elec-
tron-hole recombination was disrupted. This al-
lows the electrons to react with O2 in the solution
as shown in equation 3 to form O2
-•
. A good rea-
son for the increase in degradation rate of hydro-
chlorothiazide is possibly due to
1
O2 being formed
via reaction of O2
-•
with h
+
[17] hence, speeding up
the degradation rate of hydrochlorothiazide. It was
noted that there is insufficient research related to
the degradation of hydrochlorothiazide and its
kinetics especially in advanced oxidation pro-
cesses such as photocatalysis. Considering the
limited time given for the run of the experiments
multiple errors may have had significant effect on
the results.
3.1.3 Photocatalytic degradation of Trime-
thoprim
Figure 6(g) shows the unexpected increase in the
degradation rate of trimethoprim in the presence
of KI and TBA scavengers. The degradation rate
was decreased by NaN3 which suggests that the
controlling ROS in the degradation process was
the
1
O2. The proposed reaction pathways for the
degradation of trimethoprim with
1
O2 are shown in
Figure 3.
Figure 3: Proposed degradation pathways for the reac-
tion between
1
O2 and trimethoprim [18].
A study performed by E.M. Rodriguez et al. [4]
showed that at pH 7, •OH no longer control the
photocatalytic degradation of trimethoprim in a
suspension. This explains why the addition of KI
or TBA had no effect in oppression of degradation
rate of trimethoprim.
Dang Ho et al [19] have performed a study on
the effect of flow rate on the photocatalytic degra-
dation of trimethoprim in aqueous suspension of
TiO2 P25 Degussa under the same condition [19].
Based on the results obtained, they concluded
that in order to maximize the degradation per-
centage of trimethoprim, 30 mL/min which corre-
sponded to the hydraulic detention time (Dt) of 50
minutes should be chosen as the optimum for the
continuous system. The flow rate of the pharma-
ceutical solution used in this experiment was 500
mL/min which is comparably higher than the flow
rate used by Dang Ho et al. This could be the
reason why the degradation of trimethoprim was
very slow.
3.1.4 Photocatalytic degradation of Diclofenac
The degradation of diclofenac was rapid as the
HPLC could not detect it after 20 minutes for the
control run and TBA scavenger. The rate of deg-
radation of diclofenac was found to be significant-
ly slower with the presence of KI compared to the
control run as shown in Figure 6(e). Same result
was found with the presence of NaN3 only less
significant. The results indicate that the degrada-
tion of diclofenac relies more on h
+
compared to
1
O2 radicals. However, diclofenac was found to be
degrading at the same rate as the control run
when using TBA as scavenger which means that
•OH does not play a major role in the degradation
of diclofenac with TiO2. At neutral pH, •OH are
considered to be the major oxidising species [20].
Figure 4: Possible scheme of fragmentation pathway in
the degradation of diclofenac [21].
From Figure 4 it can be seen that the OH group is
present in one of the two aromatic rings. P.Calza
et al showed that the intermediates stoichiometric
release is achieved after 1 hour of irradiation,
when all hydroxyl and bihydroxy derivatives are
disappeared and C-N cleavage is obtained [21].
This coincides well with the experimental results
shown in Figure 5 and 6 which shows the degra-
dation rate of diclofenac under the effect of the
three different scavengers used.
5. 5
Figure 5: Photocatalytic degradation of the four pharmaceuticals: (a) without scavengers. (b) using KI as a scaven-
ger. (c) using TBA as a scavenger. (d) using NaN3 as a scavenger. Experimental conditions: ;
; ; , UVC intensity
, nm.
Figure 6: Influence of TBA (10 mM), NaN3 (5 mM) and KI (10 mM) on photocatalytic degradation of: (e) diclofenac (f)
hydrochlorothiazide (g) trimethoprim and (h) caffeine by TiO2 under UVC radiation at pH 7.5.
(a)
(b)
(c)
(d)
(e)
(f)
(g)
(h)
6. 6
4. CONCLUSION
Caffeine showed minimal degradation, however it
has been observed that the possible ROS affect-
ing the degradation are the hydroxyl and singlet
radicals. The degradation of hydrochlorothiazide
was difficult to evaluate as the degradation in-
creased in the presence of KI and decreased in
the addition of TBA and NaN3 scavengers result-
ing in the singlet oxygen radicals being the active
species. Diclofenac showed very good degrada-
tion and it has been observed that the photogen-
erated holes play a major role in its degradation
followed by the hydroxyl radicals. Trimethoprim
also showed an increase in the degradation rate
in the presence of KI and TBA scavengers and a
decrease when NaN3 was used. After observation,
it has been found that the singlet oxygen were the
active species in the degradation of trimethoprim.
The limitation of the degradation rate for caffeine
and trimethoprim could be explained by the re-
combination of the photogenerated electron-hole
(e
-
-h
+
) pairs which happens when TiO2 is used as
a catalyst, one of the ways to inhibit e
-
and h
+
re-
combination is to add an alternative e
-
acceptor to
compensate for the deficiency of O2 caused either
by slow, or by mass transfer.
5. REFERENCES
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and photocatalytic oxidation processes for the
degradation of pharmaceutical pollutants. Water
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[2] Abramović, B., et al., Photocatalytic degradation of
metoprolol tartrate in suspensions of two TiO2-
based photocatalysts with different surface area.
Identification of intermediates and proposal of
degradation pathways. Journal of Hazardous
Materials, 2011. 198(0): p. 123-132.
[3] Hernando, M.D., et al., Environmental risk
assessment of pharmaceutical residues in
wastewater effluents, surface waters and sediments.
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[4] Rodríguez, E.M., et al., Mechanism considerations
for photocatalytic oxidation, ozonation and
photocatalytic ozonation of some pharmaceutical
compounds in water. Journal of environmental
management, 2013. 127: p. 114-124.
[5] Zhao, C., et al., Role of pH on photolytic and
photocatalytic degradation of antibiotic
oxytetracycline in aqueous solution under
visible/solar light: Kinetics and mechanism studies.
Applied Catalysis B: Environmental, 2013. 134–
135(0): p. 83-92.
[6] Bhatkhande, D.S., V.G. Pangarkar, and A.A.
Beenackers, Photocatalytic degradation for
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[7] Cabrera, M.I., O.M. Alfano, and A.E. Cassano,
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Photocatalytic degradation of trimethoprim by
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8. 8
Minutes from weekly meeting with the supervisor,
Week 1
Experiment
Optical properties of photocatalytic mate-
rials
Focus on the absorption coefficient and
scattering coefficient with changing pH
and light wavelength.
Titanium dioxide will be used as the pho-
tocatalytic material for this experiment.
Research
Literature review on optical properties of
phtocatalytic materials, focusing on ab-
sorption and scattering coefficient
Use scopus.com for resources and read
the article “Experimental method to eval-
uate the optical properties of aqueous Ti-
tanium Dioxide suspension”
Week 2
Experiment
Issues with experiment proposed in terms
of meeting deadline, using only modelling
was discussed
Modelling require knowledge of coding
which could take long to finish by dead-
line.
Change of the experiment title to photo-
catalytic oxidation of pharmaceuticals
which is related to the degradation of
pharmaceuticals in the presence of free
radicals
The samples will be monitored by a HPLC
system
Produce risk assessment and coshh form
for the experiment proposed.
Meeting with phd student and supervisor
to discuss new experiment title and ar-
range a time for laboratory work.
Research
Literature review on the new title pro-
posed.
Focus on the article “Role of pH on photo-
lytic and photocatalytic degradation of an-
tibiotic oxytetracycline in aqueous solution
under visible/solar light: Kinetics and
mechanism studies”
Week 3
Experiment
Familiarisation with the HPLC machine
Gathering parts to set up the photo-
reactor
Prepare stock solutions for the four exper-
iments
Start the experiments and run samples in
the HPLC
Research
Literature review on similar experiments
in order to optimise the experiments
Week 4
Experiment
Results presented to supervisor no deg-
radation
Identify the cause of the problem
The tube used in the photo-reactor was
Pyrex and not quartz, so UV radiation
was not passing through to induce degra-
dation
Change the tube to quartz and run the
experiment again with new stock solu-
tions
Take measurements of the light intensity
using spectrometer
Research
Literature review on similar experiments
in order to optimise the experiments
Week 5
Experiment
Analysis of final results
Identify possible experimental errors
Technical report
Compare results with literature review for
analysis
Results and discussion
Week 6
Technical report
Draft presented to supervisor
Feedback analysis to enhance final report