Degradation of ibuprofen by hydrodynamic cavitation: Reaction pathways and effect of operational parameters

Article abstract of DOI:10.1016/j.ultsonch.2015.09.002

Ibuprofen (IBP) is an anti-inflammatory drug whose residues can be found worldwide in natural water bodies resulting in harmful effects to aquatic species even at low concentrations. This paper deals with the degradation of IBP in water by hydrodynamic cavitation in a convergent-divergent nozzle. Over 60% of ibuprofen was degraded in 60 min with an electrical energy per order (E_EO) of 10.77 kWh m^-3 at an initial concentration of 200 μg L^-1 and a relative inlet pressure p_in = 0.35 MPa. Five intermediates generated from different hydroxylation reactions were identified; the potential mechanisms of degradation were sketched and discussed. The reaction pathways recognized are in line with the relevant literature, both experimental and theoretical. By varying the pressure upstream the constriction, different degradation rates were observed. This effect was discussed according to a numerical simulation of the hydroxyl radical production identifying a clear correspondence between the maximum kinetic constant k_OH and the maximum calculated OH production. Furthermore, in the investigated experimental conditions, the pH parameter was found not to affect the extent of degradation; this peculiar feature agrees with a recently published kinetic insight and has been explained in the light of the intermediates of the different reaction pathways.

Full text of DOI:10.1016/j.ultsonch.2015.09.002

Ultrasonics Sonochemistry 29 (2016) 76–83
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultson
Degradation of ibuprofen by hydrodynamic cavitation: Reaction
pathways and effect of operational parameters
c
a
d
Dino Musmarra a, Marina Prisciandaro b, , Mauro Capocelli , Despina Karatza , Pasquale Iovino ,
⇑
Silvana Canzano d, Amedeo Lancia e
a Dipartimento di Ingegneria Civile, Design, Edilizia e Ambiente, Seconda Università degli Studi di Napoli, Real Casa dell’Annunziata, Via Roma 29, 81031 Aversa (CE), Italy
b Dipartimento di Ingegneria Industriale e dell’Informazione e di Economia, Università dell’Aquila, viale Giovanni Gronchi 18, 67100 L’Aquila, Italy
c Facoltà di Ingegneria, Università Campus Bio-Medico, Via Alvaro del Portillo, 21, 00128 Roma, Italy
d Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Via Vivaldi, 43, 81100 Caserta, Italy
e Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università ‘‘Federico II” di Napoli, Piazzale V. Tecchio, 80, 80125 Napoli, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 May 2015
Received in revised form 8 August 2015
Accepted 3 September 2015
Available online 5 September 2015
Ibuprofen (IBP) is an anti-inflammatory drug whose residues can be found worldwide in natural water
bodies resulting in harmful effects to aquatic species even at low concentrations. This paper deals with
the degradation of IBP in water by hydrodynamic cavitation in a convergent–divergent nozzle. Over
60% of ibuprofen was degraded in 60 min with an electrical energy per order (EEO) of 10.77 kWh mꢀ3
at an initial concentration of 200 l
g Lꢀ1 and a relative inlet pressure pin = 0.35 MPa. Five intermediates
generated from different hydroxylation reactions were identified; the potential mechanisms of
degradation were sketched and discussed. The reaction pathways recognized are in line with the relevant
literature, both experimental and theoretical. By varying the pressure upstream the constriction, different
degradation rates were observed. This effect was discussed according to a numerical simulation of the
hydroxyl radical production identifying a clear correspondence between the maximum kinetic constant
Keywords:
Emerging contaminants
Ibuprofen
Reaction mechanism
Venturi reactor
Modeling
ꢀ
kOH and the maximum calculated OH production. Furthermore, in the investigated experimental condi-
Intermediates
tions, the pH parameter was found not to affect the extent of degradation; this peculiar feature agrees
with a recently published kinetic insight and has been explained in the light of the intermediates of
the different reaction pathways.
Ó 2015 Elsevier B.V. All rights reserved.
1. Introduction
environment and human health, at present there is no regulation
limiting their concentrations in water streams. Based on the pre-
The pollution of the aquatic environment has received increas-
ing attention over the last decades because of the presence of
emerging compounds (EC), only recently quantified thanks to the
development of new analytical techniques [1,2]. These compounds
are xenobiotic and bioactive chemicals such as surfactants, phar-
maceuticals, endocrine disruptors and illegal drugs that, even at
small concentrations, can affect water quality and are potentially
harmful for the ecosystem and human health [2]. They reach the
environment via the discharge of personal hygiene products,
industrial (mainly pharmaceutical) and hospital wastes and medi-
cations. Currently, it is estimated that more than 3000 different
pharmaceutical compounds are used in the European Union and
many of them are susceptible to reach the water cycle [3]. Despite
the unpredictable negative impact of these compounds on the
caution principle, every four years the Environmental European
Agency updates the list of priority substances where pharmaceuti-
cals are included as potential pollutants. The EU Water Framework
Directive EEA 2013 [4] recognizes pharmaceuticals as a potential
risk for the aquatic environment in Europe and states that the
Commission shall develop a strategic approach to monitor and reg-
ulate this kind of pollution as far as possible.
The compound 2-[3-(2-methylpropyl)phenyl] propanoic acid,
marketed as ibuprofen (IBP, CAS number: 79261-49-7), is a
Non-Steroidal Anti-Inflammatory Drug (NSAID) (available for
over-the-counter sale) used in the treatment of rheumatic disor-
ders, fever, migraine, muscle aches, arthritis and tooth aches. The
main sources of environmental IBP contamination include indus-
trial discharges, excretory products of medically treated humans
and animals and the improper disposal of unused medications
via the toilet [5]. As many other contaminants, its fate in the aqua-
tic environment depends on biodegradability and physicochemical
⇑
Corresponding author.
E-mail address: marina.prisciandaro@univaq.it (M. Prisciandaro).
http://dx.doi.org/10.1016/j.ultsonch.2015.09.002
1350-4177/Ó 2015 Elsevier B.V. All rights reserved.

D. Musmarra et al. / Ultrasonics Sonochemistry 29 (2016) 76–83
77
properties such as solubility in water, octanol–water and organic
carbon–water partitioning coefficient [6]: natural attenuation phe-
nomena mainly include sorption on soils or sediments, sunlight
photolysis, and other abiotic transformations (i.e. hydrolysis) [7].
The conventional wastewater treatment plants (WWTP) do not
seem to effectively remove the IBP from effluents. Some recent
studies demonstrate that the conventional treatments, mainly
based on the use of microorganisms, are inadequate to effectively
destroy these organic compounds with a complex molecular struc-
ture and low concentrations [1]. For this reason, IBP can be found
in sewage influents, effluent samples and, consequently, in several
surface waters located downstream municipal WWTPs [8–12]. IBP,
as other micropollutants, can be removed by membrane filtration
or adsorption onto activated carbon; however, these two methods
can be inhibited by the natural organic matter present in water,
that also affects the fouling potential of the membranes or com-
petes for adsorption. Although there have been numerous studies
on the adsorption of aromatic compounds in aqueous solutions,
the governing mechanisms must still be established to enhance
the effectiveness of the process that still suffers from desorption-
and regeneration-related issues [13–15]. IBP is also very resistant
towards ozonation techniques [16]. For these reasons, new effec-
tive EC degradation techniques, known as Advanced Oxidation
Processes (AOPs), are currently being studied. They are based on
the generation of the hydroxyl radicals. OH-radicals are very reac-
tive and non-selective species, able to react very rapidly with
almost every organic substance. The AOPs include, among others,
Fenton-like processes, direct ultraviolet photolysis, cavitation, pho-
tocatalysis, ozone-based hybrid processes, electro-oxidation and
cavitation processes [17].
Cavitation is the formation, growth and subsequent collapse of
microbubbles in a solvent with the consequent release of large
magnitudes of energy per unit volume over an extremely short
interval of time (10ꢀ3 ms), resulting in local high pressures
(10–500 MPa) and temperatures (1000–10,000 K). The collapses
also result in the formation of highly reactive free radicals, the con-
tinuous surface and interface cleaning as well as the enhancement
of mass transfer rates due to generated turbulence [18]. The phe-
nomenon takes place because of a pressure variation due to the
presence of a constriction, designed ad hoc, or to ultrasound waves
and is nowadays considered an innovative means to enhance dif-
ferent chemical processes [19]. In the field of pharmaceutical
wastewater treatment, the application of ultrasounds was the first
to be studied and is widely described in literature [6,20–23]. It
shows promising results (also for IBP degradation) particularly if
combined with other AOPs: sonophotocatalytic degradation in
the presence of homogeneous (Fe3+) and heterogeneous photocat-
alysts (TiO2) [10,24].
mentioning the work carried out by researchers from the
University of Ljubljana who investigated the use of shear-
induced cavitation for hybrid HC/AOP [28,29]. They obtained
promising results in degrading four different pharmaceuticals in
a roto-cavitating apparatus with the addition of H2O2. They also
achieved very high efficiency with the combination of biological
treatment, UV and HC/H2O2 for similar pharmaceutical effluents
[30] demonstrating how it is possible to transpose research find-
ings into a directly employable large-scale wastewater treatment
and encouraging the research in this field.
The patented Dynajet apparatus is the only example of indus-
trial application of stand-alone HC that is effective in the degrada-
tion of a mixture of pharmaceuticals and personal care products; it
has also shown that the overall degradation extent for different
compounds increases linearly with the logKow while the pressure
has a non-linear effect on the kinetics [31]. As long as cavitation
alone is not ready to solve the issue of EC degradation, in our opin-
ion it is important to keep performing stand-alone and cavitation
experiments and to investigate its phenomenology by coupling
the experiments with numerical simulations and by analyzing
the degradation mechanisms. To this purpose, our paper is part
of a wider study carried out by our research group focused on
the experimental and theoretical insight of HC as an advanced oxi-
dation process [25,32]. Hereby we present the experimental results
on the degradation of IBP through hydrodynamic cavitation in a
convergent–divergent nozzle reactor. The effects of inlet pressure
and pH are addressed and discussed by referring to a consolidated
mathematical model [32] as well as other relevant literature. The
identification of different reaction intermediates in this work,
allowed the investigation of the reaction kinetics and the identifi-
cation of a possible mechanism of degradation that, in the light of a
thermodynamic insight and other experimental evidences, might
explain the peculiar the pH effect observed.
2. Experimental
2.1. Apparatus
Fig. 1 depicts the experimental setup. It consists of a closed-loop
reactor comprising a holding tank of 1.5 L volume with a cooling
system and two pipelines: the main line consists in the reactor pro-
vided with two pressure gauges measuring the inlet pressure (p1)
and the fully recovered downstream pressure (p2); the second
one is used to recirculate the solution bypassing the reactor. The
dimensions of the nozzle are shown in Fig. 2. Two control valves
regulate the gauge pressure and the flow rate (p1 = 0.20–
0.65 MPa; Q = 0.2–0.4 m3 hꢀ1) in the main line; the inside diameter
of both the main and the by-pass lines is 12 mm while the constric-
tion diameter is 2 mm. Further details can be found in Capocelli
Hydrodynamic cavitation (HC) has been recently considered as
an interesting opportunity to rule out the issue of the high-energy
consumption of ultrasounds. Moreover, HC can be considered a
sustainable, reliable and easy-to-handle technique. Several papers
prove the applicability of HC in degrading emerging organic pollu-
tants [25,26]. Its combination with a chemical AOP seems to have
major synergistic effects also in the treatment of pharmaceutical
micropollutants, besides the excellent results in terms of power
consumption and cost-effective system up-scaling. The most
recent research works aim at extending degradation by introduc-
ing additional oxidants. Particularly in the case of non-VOC and
hydrophilic substances, it is common opinion that, in industrial
WWT, the cavitation has to be coupled in hybrid AOP solutions
(e.g. with H2O2, UV, Fenton). Bagal and Gogate [27] studied the
degradation of diclofenac by optimizing a HC hybrid technique
(95% degradation using UV/TiO2/H2O2 and hydrodynamic cavita-
tion in a Venturi nozzle at 3 bar and pH 4). It is also worth
et al. [24]. The IBP initial concentration was 200 lg/L, the initial
pH was varied in the range 2–9; the temperature was kept during
the experiments below the limit of Tw = 25 °C. During testing, 1 ml
samples were drawn from the test reservoir and analyzed as
described in the next section.
2.2. Materials and methods
An ibuprofen sodium salt of analytical grade with purity
higher than 98% purchased from Sigma–Aldrich (UK) was used
for the experimental activities. The analytical measurement of
the total IBP in solution was performed by Gas-Chromatography
coupled with Mass Spectrometry (GC/MS) after a solid phase
extraction (SPE) step. The SPE step consists in the isolation of
the pharmaceuticals from the water samples through
a

78
D. Musmarra et al. / Ultrasonics Sonochemistry 29 (2016) 76–83
pHc
FI
TIC
FLOW INDICATORS
LIC
COOLING
SYSTEM
PRESSURE
TRANSDUCERS
P1
P2
PI
SAMPLING
PI
PUMP
VENTURI
Fig. 1. Layout of the experimental apparatus.
Fig. 2. Details of the Venturi reactor.
reversed-phase cartridge (Oasis HLB 1 cc, Waters) and the extrac-
tion of samples under vacuum at flow rate of 5 ml/min. Each car-
tridge was pre-conditioned with 3 ml of methanol (analytical
grade, Fluka) followed by 5 ml of ultra-pure water. After extrac-
tion, the cartridges were dried under vacuum for 10 min. Ibupro-
fen was eluted with 3 ml of methanol. The extracts were dried
(SIM). A calibration (5 points) with standard solutions in CH2Cl2
was used for quantification. The oven temperature was held at
70 °C for 1 min, then programmed at 10 °C/min to 300 °C which
was held isothermally for 2 min. The temperatures of injection
port, transfer line, source and quadrupole temperature were
250, 280, 230 and 150 °C.
under
a
stream of nitrogen. The final volume extracted is
The byproducts generated by the HC treatment were identified
by a LC–MS/MS analysis [33]. The LC analysis was performed using
a Waters 2690 HPLC system (Milford, MA, USA) coupled to a triple
quadrupole mass spectrometer (Waters Micromass Quattro),
equipped with a Z-spray ESI interface (Manchester, UK). The anal-
ysis was carried out in multiple reaction monitoring mode, both in
positive and negative electrospray ionization mode.
100 l. The determination of IBP in solution was made by means
l
of a 7890A gas chromatograph with a mass spectrometric detec-
tor MSD5975C (Agilent Technologies, USA), equipped with a cap-
illary column HP-5MS (5% phenylmethylsiloxane; length of 30 m;
internal diameter of 0.25 mm, film thickness of 0.25
analytes were detected and quantified in selective ion monitoring
lm). The

D. Musmarra et al. / Ultrasonics Sonochemistry 29 (2016) 76–83
79
3. Results and discussion
3.1. Kinetic effect of inlet pressure
The degradation of IBP was evaluated through sampling at dif-
ferent times, at four pressure levels; the system appeared ineffec-
tive outside of the range of pressure considered (0.20–0.55 MPa).
The dimensionless concentration of IBP versus the experiment
duration is shown in Fig. 3.
The degradation extent increases with different rates depending
on the inlet gauge pressure pin: the final conversion is higher at
pin = 0.35 MPa, followed by pin = 0.45 MPa, pin = 0.55 MPa and
pin = 0.20 MPa respectively. The IBP degradation rate was written
according to the analysis by Capocelli et al. [25] by assuming that
the reactor is a stationary source of hydroxyl radicals and the
kinetics can follow an exponential equation with a pseudo-first
order constant as shown in Eq. (1) where [OH]s is the stationary
ꢀOH concentration. Therefore, by assuming a solution residence
Fig. 4. Reactor model for the kinetics estimation.
Table 1
Experimental parameters and results. pH = 6. T = 25 °C.
time
s in the reactor, the IBP conversion follows the Eq. (2) law.
Fig. 4 represents the reactor model to write a first order degrada-
tion rate for the observable concentration IBP(t) through the mass
balance to the tank control volume, Eq. (3). It is obtained by assum-
ing that the reaction occurs only in the reactor of volume V0 (rep-
resentative of the cavitation extension) and the time scale of the
variation in concentration is far higher than the residence time into
the lines, in similarity to our previous work [25].
Inlet
Flow rate into
the Venturi, W
(1 ꢀ u) (L/min) Cv (–)
Cavitation
number,
Pseudo-first
order rate
constant, k
Electrical
energy per
order, EEO
pressure,
pin (bar
gauge)
(minꢀ1
)
(kWh mꢀ3
)
2
3.504
0.56
0.39
0.32
0.26
0.0152
0.0850
0.0928
0.0383
28.83
10.77
14.07
45.68
3.5
4.5
5.5
4.17765
4.62675
5.07585
d½IBPꢁ=dt ¼ ꢀkOH½OHꢁs½IBPꢁ ¼ ꢀk½IBPꢁ
ð1Þ
ð2Þ
IBPð
s
Þ ¼ IBPð0Þ ꢂ expðꢀk ꢂ
s
Þ
pressure has in the optimization of cavitation as an AOP. The non-
monotonic effect of pin (and cavitation number) observed in this
study, has already been mentioned in the literature as in the case
of HC combined with heterogeneous photocatalysts of diclofenac
sodium [27]. Vichare et al. [36] also showed similar results for KI
decomposition in different orifice plates finding the best operating
conditions at a certain value of pin. Yan and Thorpe [37] identified
a critical cavitation number for the onset of chocked cavitation,
which corresponds to the decreased efficiency for pin > 4.5 bar, seen
in this paper. Also Capocelli et al. [32] gave a quantitative evalua-
tion of the reasons beyond the optimal operating conditions. The
first one, more intuitive, is that there are more passes through the
HC reactor when pin is higher. Secondly, the intrinsic dependence
of the degradation on the pin, is ascribable to the production of
hydroxyl radicals by the collapse of the cavitating bubbles (seen
ꢀ
ꢀ
ꢀ
ꢀ
ꢃ
ꢁ
ꢂ
ꢄ
dIBP
dt
Wð1 ꢀ
u
Þ
V0
¼
ꢂ
exp ꢀk ꢂ
ꢀ 1 ꢂ IBP
ð3Þ
V
W ꢂ ð1 ꢀ
u
Þ
obs
where W is the total flow rate and u is the recirculating ratio. There-
fore, by interpolating the experimental results of Fig. 3, it was pos-
sible to estimate the intrinsic reaction kinetic constant k from
Eq. (3). The operating values describing the experiments reported
in Table 1: the flow rate of fluid passing through the constriction,
the cavitation number and the estimated pseudo-first order kinetic
constant. On this basis the electrical energy consumption per order
E
EO [34] has been calculated for all the inlet pressure and it is found
to be minimum for pin = 0.35 MPa. Although the value can be
reduced by the implementation of hybrid techniques, it is compara-
ble with the range indicated by the literature for UV treatment [35].
The results in Table 1 highlight the intrinsic role that the inlet
ꢀ
as a stationary sources of OH [22]).
As a matter of fact, IBP conversion occurs mainly by reaction
with hydroxyl radicals at the bubble–liquid interface; indeed the
concentration inside the bubbles and in the liquid bulk is negligible
due to its hydrophobic and low volatility character (logKow = 0.56
at neutral pH and H = 1.51 atm m3/mol at 25 °C) [22]. Therefore,
in Fig. 5 we propose a comparison between the observed kinetic
constant and the estimated hydroxyl radical production rate. The
pseudo-first order constants are taken from Table 1; the global
ꢀOH production (grey line) is obtained by integrating the single
bubble dynamics over the initial nuclei population as reported in
our previous work [22]. The model consists of: (i) Rayleigh–Plesset
equation for the radial motion of the spherical bubble; (ii) equation
for the diffusive flux of water vapor (gas diffusion is ignored);
(iii) overall energy balance applied at the cavitation bubble open
system; (iv) continuity equation; (vi) Bernoulli equation; (vii) cav-
itation event rate as the number of nuclei of a specific size that
actually cavitate as a consequence of the hydraulic regime. Main
assumption: (1) fragmentation and coalescence phenomena are
neglected; (2) uniform pressure and temperature inside the bub-
ble; (3) temperature–pressure profile stationary in the liquid bulk
and at the bubble wall; (4) at the collapse stage, the bubble content
1.0
0.8
0.6
0.4
0.20 MPa
0.35 MPa
0.45 MPa
0.55 MPa
0.2
0.0
0
10
20
30
40
50
60
time [min]
Fig. 3. IBP concentration versus time at different pin
.

80
D. Musmarra et al. / Ultrasonics Sonochemistry 29 (2016) 76–83
is modeled as a reactive mixture of compounds that cannot get out
of the bubble. The equilibrium mole fraction of the entrapped
chemical species at the peak conditions reached during the tran-
sient collapse is estimated by minimizing the Gibbs free-energy.
The peak of production, recognized around pin = 0.45 MPa, cor-
responds to the maximum of IBP conversion rate observed in our
experiment and gives a further confirmation of the reaction mech-
anism (above mentioned and summarized by Eq. (1)) triggered by
[38]. Through the density functional theory, these authors com-
pared all the possible mechanisms of OH on IBP attack: the bond
ꢀ
dissociation energy (BDE) in case of hydrogen abstraction for the
benzylic carbons (C11 and C24) characterizing the intermediates
B and C is lower than that of the primary carbons. A similar BDE
can be found for H abstraction at the tertiary carbon (C14) for
the generation of compound A. Table 2 reports the resulting kinetic
constants. Subsequent secondary reactions of the carbon radical
could lead to exothermic decarboxylation and secondary oxidation
leading to a ketone group with a low activation barrier: the second
step, decarboxylation, can occur very easily and can contribute to
the formation of the oxidized products as in the literature [10,21]
and expressed in the intermediates D and E. The time sequence
of the reaction products observed in this paper endorses the
hypothesized mechanisms, also confirming that the technique
can be an effective AOP initiator for IBP degradation like in other
sonochemical environments [10]. Although it is not possible to
observe the mineralization of the pollutant in the experimental
conditions investigated, the HC treatment promotes the oxidation
of IBP and its biodegradability by triggering the hydroxylation
ꢀ
the OH released from the collapsing bubbles.
3.2. Reaction pathways
In order to identify the reaction intermediates, the samples col-
lected at various time intervals were analyzed by means of LC–MS/
MS. Fig. 6 shows the temporal sequence of intermediate formation
for three different sampling times; by extending the treatment
time, six prominent peaks were identified. The results show the
ꢀ
formation (clearly visible at t = 60 min) of products from the OH
attack on both the propanoic acid and isobutyl substitutes of the
IBP structure as:
process followed by
de-carboxylation.
a second step of de-methylation or
A. 2-[4-(2-hydroxyisobutyl)phenyl]propionic acid
B. 2-[4-(1-hydroxyisobutyl)phenyl]propionic acid;
C. 2-hydroxy-2[4-(2methylpropyl)phenyl]propanoic acid.
3.3. The effect of initial pH
The reaction pathways with the intermediate chemical struc-
tures are shown in Fig. 7. They are generated in the first place by
the acidic hydrogen abstraction, which dominates over the other
ꢀOH addition mechanisms and can produce two different benzylic
carbon radicals at C11 and C24 and a tertiary radical C14 (as pro-
ven by products A, B and C). The identification of these intermedi-
ates also corroborates the assumption of the kinetic mechanisms of
Eqs. (1) and (2) and are in line with the experimental observations
in the literature [22,24], where no oxidation product for the pri-
mary carbons is observed. By extending the duration of the exper-
iments, the decomposition of compound A, through the cleavage of
the C1–C2 bond of the isobutyl functional group, forms two inter-
mediates, 2-(4-methylphenyl)propanoic acid (D) and ketone ace-
As it is a crucial parameter in wastewater treatment, the pH was
varied to investigate its effect on the IBP degradation. The molecule
studied is a non-volatile compound and the region of degradation
would be outside the cavitation bubbles. The IBP concentration at
the hydrophobic bubble interface is clearly influenced by the solu-
tion pH: above its pKa value of 4.9, the anionic IBP [Aꢀ] is predom-
inant, while at lower values IBP is principally found in its
molecular form [HA]. In our experiments, the degradation of both
ionic and neutral forms of IBP was carried out choosing initial pH
values of 2, 9 and 6. The results are illustrated in Fig. 8; the gauge
inlet pressure was fixed at the optimized value of pin = 0.45 MPa. As
a general remark it can be said that pH does not affect the IBP
degradation rate; a slight decrease in the degradation rate of IBP
under acidic media was observed following the order pH 9 > pH
6 > pH 2. This could be tell-tale of two phenomena acting in
contrast.
tone. Furthermore, the decarboxylation of the compound
C
results in the formation of 4-isobuthylacetophenone (E) releasing
formic acid. The disappearance of compounds A and B generating
D and E is visible in Fig. 6 at t = 150 min.
In order to explain the observed pathways it is interesting to
analyze the thermodynamic and kinetic parameters of the reaction
between ibuprofen and hydroxyl radical identified by Xiao et al.
On the one hand, an increased hydrophobicity (protonation of
the carboxylic group) results in a higher concentration at the inter-
face of cavitation bubbles, thus leading to a faster degradation rate
at low pH. On the other hand, the reaction pathway IBP ? C ? E
(see Fig. 7) has been significantly observed only for the anionic
form of IBP. This experimental evidence is supported by the result
of quantum mechanics recently developed by Xiao et al. [38]
4
3
2
1
0
0.10
0.08
0.06
0.04
0.02
0.00
ꢀ
While the energy profile for the common OH reactions is similar
in case of neutral and anionic IBP, the energy barrier for H25
abstraction in position C24 (see C ? E in Fig. 7) is significantly
lower than for neutral IBP:
D
G° = ꢀ7.67 ꢂ 10ꢀ2 kcal/mol against
D
G° = 6.56 kcal/mol [38]. The results of kOH, showing the preferable
pathway that generates observable concentration of compounds C
and E from the anionic IBP, are visible in Table 2. Therefore, in
our case, the pH influences the reaction mechanisms with a
phenomenology that differs from the classical view of the
sonochemical degradation of non-VOC substances seen as an issue
of hydrophobicity and pollutant adsorption at the bubble interface
[10,22].
OH production
pseudo-first order constant
.
0.1
0.2
0.3
0.4
0.5
0.6
0.7
p
in [MPa]
4. Conclusions
Fig. 5. Effect of the inlet pressure pin: observed pseudo-first order kinetic constant
of IBP conversion (N); theoretical, stationary ꢀOH rate of production in the
experimental apparatus (grey line).
This study presents the evidence that hydrodynamic cavitation
alone is effective in the degradation of ibuprofen, both in the

D. Musmarra et al. / Ultrasonics Sonochemistry 29 (2016) 76–83
81
Fig. 6. Temporal sequences of intermediate identification. pin = 0.45 MPa. Time 0–150 min.
neutral and dissociated form. More than 60% of ibuprofen was
degraded within 60 min with a EEo of 10.77 kWh mꢀ3 at an
pin = 0.35 MPa without the use of additive chemicals. The effect
of inlet pressure has been addressed and compared with literature
data: the peaks of the kinetic constants related to pin seem to
initial concentration of 200 l
g Lꢀ1 and a relative inlet pressure

82
D. Musmarra et al. / Ultrasonics Sonochemistry 29 (2016) 76–83
Fig. 7. Intermediates identified and possible degradation pathways by hydrodynamic cavitation of IBP.
Table 2
match the numerical simulation of the hydroxyl radicals produced
in the Venturi reactor, which is an additional proof that the IBP
degradation passes through the collision with OH at the interface
of the collapsing bubbles. The experimental work therefore repre-
sents the basis to design and develop advanced treatment schemes
including hydrodynamic cavitation for the treatment of pharma-
ceutical wastewaters.
Furthermore the paper reports an innovative comprehensive
approach by coupling experimental observations with numerical
simulations and thermodynamic analysis (from pertinent litera-
ture) in order to figure out the process phenomenology from differ-
ent complementary point of views. A possible reaction scheme has
been identified and explained in the light of quantum mechanics as
in the literature. The comparison with the rigorous thermodynamic
model also validates the reaction mechanisms and indirectly the
simulation model. Thanks to the experimental methods and the lit-
erature review, a degradation pathway has been identified and, for
the first time, related to a plausible explanation of the pH effect.
Although this differs from the data in the literature, it can be fully
explained on the basis of the kinetic analysis developed. The mech-
anisms identified at different pH should be studied in further
experiments at different IBP initial concentrations in order to fig-
ure out the behavior in both kinetic or diffusion controlled regimes.
Rate constants for the transition state species involved in the reactions of neutral and
anionic form of ibuprofen with OH extracted from the work of Xiao et al. [38].
ꢀ
Reaction mechanism
Atom number
k (Mꢀ1 sꢀ1
)
Neutral form
H abstraction
C11
C14
C24
C30
2.76 ꢂ 109/9.59 ꢂ 107
1.50 ꢂ 109
1.41 ꢂ 108
Nucleophilic attack
2.74 ꢂ 10ꢀ3
Anionic
H abstraction
Nucleophilic attack
C24
C30
7.40 ꢂ 109
3.88 ꢂ 10ꢀ2
1.0
0.8
0.6
0.4
0.2
0.0
pH 2
pH 6
pH 9
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