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Influences of solution chemistry and polymeric naturalorganic matter on the removal of aquatic pharmaceuticalresiduals by nanofiltration

Mohammad Ali Zazoulia,b, Heru Susantoa,d, Simin Nasseric, Mathias Ulbrichta,*aLehrstuhl fur Technische Chemie II, Universitat Duisburg-Essen, 45117 Essen, GermanybDepartment of Environmental Health Engineering, Faculty of Health, Mazandaran University of Medical Sciences, Sari, IrancDepartment of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, IrandDepartment of Chemical Engineering, Universitas Diponegoro, Indonesia

a r t i c l e i n f o

Article history:

Received 15 January 2009

Received in revised form

24 March 2009

Accepted 8 April 2009

Published online 3 May 2009

Keywords:

Polymeric natural organic matter

Nanofiltration

Pharmaceuticals removal

Fouling

* Corresponding author. Fax: þ49 201 183 314E-mail addresses: zazoli49@yahoo.com (M

0043-1354/$ – see front matter ª 2009 Elsevidoi:10.1016/j.watres.2009.04.038

a b s t r a c t

This study demonstrates the removal efficiency and the permeate flux behavior during

cross-flow nanofiltration (NF) of aqueous solutions of five pharmaceutically active

compounds (PhACs). Cephalexin, tetracycline, acetaminophen, indomethacin and amoxi-

cillin were used as models of PhACs, and alginate was selected as model of natural organic

matter (NOM). Two commercial composite NF membranes (SR2 and SR3) with different

characteristics were used. The highest rejection was observed for tetracycline, i.e., 75–95%

for membrane SR 2 and 95–100% for membrane SR 3, while the rejection was least for

acetaminophen (32–36% for SR2 and 52–59% for SR3). As the pH of acetaminophen solution

was increased (from 6 to 9) the rejection would increase. Changes of ionic content (from 10

to 20 mM) lead to increase (from 89 to 93% for SR 3) or decrease (from 100 to 91% for SR2) of

cephalexin rejection depending on the membrane used. The permeate flux would decrease

with decreasing the pH solution and increasing ionic strength. The addition of alginate in

the feed stream decreased the permeate flux, with lower reduction for SR3, and increased

the PhAC rejection except for acetaminophen and amoxicillin. Both size and Donnan

exclusions seemed to occur, and the effect of Donnan exclusion was more pronounced

for the NF membrane having larger effective pore size (SR2).

ª 2009 Elsevier Ltd. All rights reserved.

1. Introduction subsequently used to augment drinking water resources. It

Nowadays, pharmaceuticals are being used for healthcare as

well as for promoting good health. Thousands of pharma-

ceutical substances have been produced in huge quantities.

The release of pharmaceutically active compounds (PhACs) or

pharmaceutical and personal care products (PPCPs) into the

aquatic environment such as domestic effluents is potentially

associated with a human health risk because such water is

7..A. Zazouli), mathias.ulb

er Ltd. All rights reserved

was reported in studies since the late 1980s that PPCPs occur

in many domestic effluents (Kolpin et al., 2002; Ternes, 1998;

Ternes et al., 2002, 2004). Meanwhile, more than 50 PhACs

from various prescription classes such as analgesics, antibi-

otics, antiepileptic, anti-rheumatics, beta blockers, chemo-

therapeutics, steroid hormones, and X-ray contrast media and

their metabolites have been detected in the aquatic environ-

ment within the concentration range of micrograms per liter

richt@uni-due.de (M. Ulbricht)..

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 0 3271

(Drewes et al., 2001; Nghiem et al., 2005). While PhACs are

often not fully assimilated by humans and animals during

treatment, they are then continuously released to the envi-

ronment mostly via domestic wastewater effluent in their

original or partially metabolized forms (Nghiem et al., 2005).

PPCPs enter the wastewater after their regular use during

showering or bathing.

Because many PhACs and PPCPs have limited biological

degradability, they are only partially eliminated during treat-

ment in conventional wastewater treatment plant. Therefore,

removal of pharmaceutical substances before entering the

aquatic environment as well as the water reuse plant is very

important. In the last decade, nanofiltration (NF) or reverse

osmosis (RO) have been proposed as an attractive technology

for removal of organic micropollutants including PhACs and

endocrine disrupting compounds (EDCs) from aquatic envi-

ronment instead of conventional wastewater treatment

(Agenson and Urase, 2007; Kimura et al., 2003a, b, 2004;

Nghiem and Schafer, 2004; Nghiem et al., 2005; Radjenovic

et al., 2008; Shim et al., 2008; Van der Bruggen and Vande-

casteele, 2003; Verliefde et al., 2008, 2009). The separation

mechanism has also been explained in those references.

Furthermore, the adsorption of hydrophobic compounds

including PhACs and EDCs onto NF/RO membrane has been

investigated by Kimura et al. (2003a, b). The results showed

that the observed adsorption, which was influenced by the

charge of compound and operating condition, in dynamic

filtration tests was more significant than that in static batch

adsorption. Further, they have also investigated the rejection

of EDCs and PhACs (Kimura et al., 2004). It was reported that

the molecular weight of the tested compounds correlated with

the rejection tendency for polyamide membranes while the

polarity was better able to describe the rejection tendency of

cellulose acetate membranes. Nevertheless, for negatively

charged compounds, electrostatic interaction was the most

dominant parameter to explain the membrane rejection

(Kimura et al., 2003a, b). Nghiem et al. (2005) reported that very

high retention of sulfamethoxazole, carbamazepine, and

ibuprofen could be achieved by NF membranes. A systematic

study on the effect of electrostatic interactions on rejection of

organic solutes has also been reported recently (Verliefde

et al., 2008, 2009). In sum, the retention of pharmaceutical

substances by NF membranes is influenced by the physico-

chemical properties of the organic solute (molecular weight,

charge), the solution chemistry (ionic environment, pH, and

concentration), the membrane characteristics (surface charge,

pore size) and the process conditions (pressure, permeation

rate, cross-flow velocity/stirring rate).

Table 1 – General characteristics of NF membranes provided b

Type of TFC membrane MgSO4 La

Flux (L m�2 h�1) Rejection (%) Flux

SR2 74 96.8

SR3 39 99.6

a NF test conditions: MgSO4: 0.5% in water at 6.5 bar; lactose: 5% in wate

Although many previously reported publications have

studied the removal of organic micropollutants by NF, much

less attention had been devoted to complex feed streams. In

fact, a feed stream that shall be treated contains not only

those substances but also other components. Natural organic

matter (NOM) is one of the components that are usually

present in many aqueous feed streams. This may influence

the removal efficiency of pharmaceutical substances by NF.

Further, NOM can promote to exacerbate the flux decline

during NF. It was reported that NOM is one of the strong

foulants during water treatment using membrane processes

(Zhang et al., 2006). NOM can generally be divided into two

fractions, i.e., hydrophobic (humic) and hydrophilic (non-

humic) substances. NOM is typically dominated by humic

materials, but proteins, polysaccharides, and other classes of

biopolymers also occur (Zazouli et al., 2007). Different results

of the effect of NOM on organic substance removal by NF had

been reported in many previous studies: NOM could either

increase (Devitt et al., 1998) or decrease (Nghiem et al., 2002)

the retention of organic substances by NF membranes. No

significant effect of NOM on retention was also reported in

one study by Taylor et al. (2000). Further, the effects of

organic foulants from secondary wastewater treatment

effluent or landfill leachate on the removal of micro-

pollutants during RO/NF have been investigated in previously

reported studies (Xu et al., 2006; Agenson and Urase, 2007).

Recently, performance of NF and RO applied in a full-scale

drinking water treatment plant using groundwater for the

removal of various pharmaceuticals has been investigated

(Radjenovic et al., 2008). They showed that the removal of

neutral substances was mainly driven by size exclusion,

while for charge substances no systematic trends were

observed. More recently, Verliefde et al. (2009) investigated

the influence of membrane fouling by different surface

waters on rejection of PhACs by NF membranes. It was

observed that the resulting fouling and its consequence are

dependent on the pre-treatment used before the NF process.

In sum, many studies dealing with removal of organic

micropollutants from real water streams by NF/RO have been

reported. However, quite different results have been

obtained. Certainly, the variety of commercially available

PhACs and PPCPs as well as membranes used would be the

most probable reason for these different results.

The aim of this study was to investigate the effect of

polymeric NOM on the removal efficiency of five PhACs having

different physicochemical properties, which are cephalexin,

tetracycline, acetaminophen, indomethacine and amoxicillin,

by using two different commercial NF membranes. These

y manufacturer.a

ctose (MW¼ 342 g/mol) Glucose (MW¼ 180 g/mol)

(L m�2 h�1) Rejection (%) Flux (L m�2 h�1) Rejection (%)

62 98.3 85 70

45 99.9 37 98.7

r at 14 bar; glucose: 1% in water at 6.5 bar.

lin

e

nd

Ro

wla

nd

,2006)

)

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 03272

selected substances are popular drugs in human medical care

as analgesic and antibiotic compounds. The effects of NOM on

removal performance (retention) and permeate flux behavior

are described and discussed. Thus, it is expected that the

results of this study will complement and reconcile findings in

previous publications.

Ta

ble

2–

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(g/m

ol)

151.1

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9444.4

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3p

Ka

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(Seegers

et

al.

,1980

)2.7

(Ma

rrie

ret

al.

,2001)

2.5

6;

6.8

8(B

en

kh

eli

faet

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,1996)

4.2

(Ta

nig

uch

iet

al.

,1997)

3.3

;7.7

;9.7

(Ro

dgers

a

4lo

gP

0.5

1(A

dla

rdet

al.

,1995)

0.8

7(P

yk

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,2006)

0.0

76

(Da

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�1.3

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,2006

2. Materials and methods

2.1. Materials

Commercial thin film composite (TFC) NF membranes from

Koch, USA, were used. Table 1 shows the general character-

istics of those two membranes. Acetaminophen, amoxicillin,

cephalexin, indomethacin, tetracycline (shown in Table 2) and

alginate acid sodium salt were purchased from Fluka Chemie

AG (Buchs, Germany). Sucrose was purchased from Acros,

Geel, Belgium. Magnesium sulfate (MgSO4) and sodium chlo-

ride (NaCl) were purchased from Sigma Aldrich GmbH, Seelze,

Germany, and Carl Roth GmbH, Karlsruhe, Germany, respec-

tively. Potassium chloride (KCl), potassium hydroxide (KOH),

and hydrochloric acid (HCl), all of p.a. quality, were purchased

from Bernd Kraft GmbH, Duisburg, Germany. Sulfuric acid was

from J.T. Baker, Holland. Water purified with a Milli-Q system

from Millipore was used for all experiments.

2.2. Analyses

The concentrations of acetaminophen, amoxicillin, cepha-

lexin, indomethacin, and tetracycline were determined from

their UV absorbance at 244, 229, 262, 265, and 360 nm, respec-

tively (measured using the UV-Visible spectrophotometer

CARY-50 Probe Varian, Germany). In some cases, a Dionex

high-performance liquid chromatography (HPLC) system

equipped with a reversed phase column Discovery C18 (Per-

fectSil Target ODS-3) was used. Ammonium acetate (0.01 M) in

actetonitrile delivered at a constant flow rate of 0.3 mL/min

was used as the mobile phase for gradient elution. Each anal-

ysis lasted 39 min, and the injection volume was 20 mL.

Conductivity and pH of the solution were measured by using

a conductivity meter (CG854 model, Germany) and a digital pH-

meter (WTW pH 525 model, Germany).

2.3. Feed solutions and nanofiltration experiments

Ultra pure water (Millipore Milli-Q) was used for the prepara-

tion of all stock solutions and membrane performance

experiments. The pH of the solution (6, 7.5 or 9) was obtained

by adjusting with addition of either NaOH (0.1 N) or HCl (0.1 N)

solution. Salt stock solutions were prepared using NaCl

dissolved in ultra pure water. In all filtration experiments,

background electrolyte solution contained NaCl (either 10 or

20 mM), and the concentration of PhAC was 500 mg/L.

The filtration experiments were conducted using a cross-

flow laboratory-scale membrane test unit which mainly con-

sisted of feed tank (5 L), pump and membrane cell (Fig. 1). The

membrane cell, the spacer inserted in the membrane cell, and

all of the tubes were made of stainless steel. Full circulation

mode was used during the experiments, i.e., the retentate and

Pump

Membrane cell

V-1 V-2

Retentate

Permeate

Sampling

Feed tank

Thermostat

V-3

Pressureguage

Fig. 1 – Flat-sheet cross-flow testing cell used in this study.

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 0 3273

permeate were returned to the feed reservoir in order to

maintain constant concentrations. For each experiment,

a new membrane disk with the effective membrane area of

20 cm2 was used. The experiments were conducted at room

temperature (22� 1 �C) controlled by a water bath. All exper-

iments were done at three different transmembrane pres-

sures, i.e. 7.5, 10 and 12.5 bar. Before use for experiments, the

membranes were soaked overnight in water to remove

impurities left over from the manufacturing process or addi-

tives used for stabilization. Pure water was firstly filtered for at

least 1 h until an approximately constant flux was observed.

During fouling experiments, the permeate flux over time was

measured. For certain times, drug concentrations of feed,

permeate and retentate were analyzed. Rejection of PhAC was

calculated according to Eq. (1)

Rð%Þ ¼�

1� Cp

Cf

�� 100 (1)

where R is the rejection (%), and Cf and Cp are the solute

concentrations in feed and permeate, respectively.

2.4. Adsorptive fouling tests

The experiments were performed using a dead-end stirred cell

filtration system. The system consisted of a filtration cell

(Amicon cell, Millipore) connected to a reservoir (450 mL), and

it was pressurized by nitrogen. Experiments were conducted at

a constant pressure of 5 bar. All fluxes of pure water were

measured (by gravimetric method) until the consecutively

recorded values were considered constant, i.e., the differences

in flux for consecutive time intervals of 20 min were less than

2%. In these experiments, the water flux was initially

measured and then PhAC solution (10 g/L) was added to the cell

and the outer membrane surface was exposed to this solution

for 3 h without any flux at a stirring rate of 300 rpm. The PhAC

solution was then removed, and the membrane surface was

rinsed two times by filling the cell with pure water (5 mL) and

shaking it for 30 s. Water flux was again measured, and water

fluxes before and after exposure were compared. The evalua-

tion of membrane performance was done by calculating the

relative water flux reduction according to Eq. (2)

RFR ¼ J0 � Ja

J0� 100% (2)

where RFR is the relative water flux reduction, and J0 and Ja are

water flux before and after exposure (adsorption), respectively.

2.5. Measurement of zeta potential

The membrane surface charge was investigated by measuring

the outer surface streaming potential. The experiments were

carried out in a flat-sheet tangential flow module (Susanto and

Ulbricht, 2005). After washing with water, the membrane was

equilibrated by soaking in 0.001 mol/L KCl solutions overnight.

Two NF membranes (with 3� 6 cm dimensions) were placed

above and below the spacer, with the active layers of both

samples facing the flow channel. The electrolyte solution was

pumped by a variable-speed pump drive from Vancouver, USA

(model 120–00, Series E 221317). Pressure was measured using

a pressure transducer by Setra Systems, USA (model 280 E).

The streaming potentials of membranes were measured using

0.001 mol/L KCl solution, in the range of pH of 3–10 (at the pH

higher than 10, the electrode is unstable and at the pH lower

than 3, the conductivity of the solution will be too large and

disturb the measurement) and at a temperature of 25� 1 �C.

The pH was measured using a pH-meter by Radiometer

Copenhagen (PHM 62 Standard) and adjusted by addition of

KOH and HCl solutions. The conductivity was recorded by

WTW microprocessor conductivity meter LF 535. At each pH,

the pressure was then step-wise increased (in the range of 65–

100 kPa). A digital voltmeter by Volt Craft, Germany, was used

to measure the streaming potential. The zeta potential z was

determined using the Helmholtz–Smoluchowski equation (Eq.

(3); cf. Mockel et al., 1998)

0,4

0,5

0,6

0,7

rb

an

ce

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 03274

z ¼ kh

e0e

DEDP

(3)

where, DE is the streaming potential, DP is the hydrodynamic

pressure difference, h is the viscosity, e is the dielectric

constant of the solvent, e0 is the permittivity of vacuum, and k

is the conductivity of the solution.

0

0,1

0,2

0,3

50010001500200025003000350040004500Wavenumbers (cm-1)

Ab

so

TFC-SR2

TFC-SR3

Fig. 2 – ATR-IR spectra of the two NF membranes (after

washing with water and drying).

2.6. Measurement of contact angle

The contact angle (CA) was measured by using the static

captive bubble method. Membranes were inverted (active

layer to the bottom) in pure water at a temperature of

21� 1 �C. An air bubble was injected from a syringe under the

sample surface in water. An optical contact angle measure-

ment system (OCA 15 plus; Data physics, Germany) was used,

and at least five measurements of bubbles were averaged to

obtain contact angle of the membrane.

2.7. Membrane surface chemistry by attenuated totalreflection infrared spectroscopy

The attenuated total reflection infrared spectroscopy (ATR-

IR) technique was used to investigate chemical surface

structure of the membrane. Spectra were measured by using

a Bruker Equinox 55 instrument (Bruker Optics Inc., Billerica,

MA, USA) equipped with a liquid nitrogen detector. All

spectra were collected between 4000 and 400 cm�1, averaging

32 scans at a nominal instrument resolution of 4 cm�1, using

a diamond crystal; the temperature was 21� 1 �C. A program

written for the Opus software from Bruker was used to

calculate difference spectra versus the corresponding back-

ground spectra.

3. Results

3.1. Membrane characterization

The membrane performance is very much influenced by the

membrane and the feed solution characteristics. Hydraulic

permeability, rejection of various solutes, membrane chem-

istry, membrane wettability and membrane surface charge

were investigated. Table 3 shows the hydraulic permeability,

the rejections of sodium chloride, magnesium sulfate, sucrose

and glucose and the membrane contact angle of the NF

Table 3 – Characteristics of the NF membranes obtained from

Membrane Pure water permeability(L m�2 h�1 bar�1)

NaCl rejection(%)a

MgSO4 re(%)b

SR2 7.5 24 92

SR3 2.1 38 93

a Experimental conditions: 10 mM NaCl in water at 10 bar, pH¼ 7.5.

b Experimental conditions: 5 mM MgSO4 in water, 5 bar, pH¼ 7.5; MgSO4

c Experimental conditions: 1 mg/L in water, 5 bar, pH¼ 7.5; sucrose and

d Average value� standard deviation.

membranes used. It is seen that the membrane SR2 was more

permeable than membrane SR3 but it had lower solute rejec-

tion. The ATR-IR spectra of two fresh membranes (after

washing with water and drying) presented in Fig. 2 show that

both thin active layer and base membrane could be detected.

Such observation has also been obtained in previously

reported studies (Kim et al., 2008; Mondal and Wickrama-

singhe, 2009). More importantly, the ATR-IR spectra suggest

that the active layer materials of the two membranes were

basically very similar; only peaks in the band areas 3200–

3500 cm�1 (N–H stretch of amide), 1640–1650 cm�1 (NH bend of

amide) and 1720–1750 cm�1 (C]O stretch of carboxylate or

ester) show different intensity. Peaks at w1240, w1490 and

w1580 cm�1, which cannot be related to polyamide but are

typical for aromatic polysulfone, were also observed. The

contact angle (CA) data, which indicate the hydrophilicity of

the membranes, show that both membranes had CA within

the range of a hydrophilic material (lower than 60� (Vogler,

1999)). However, the membrane SR3 was slightly more

hydrophobic than the membrane SR2. Zeta potential data

presented in Fig. 3 show that the surface of both NF

membranes had a negative charge and the absolute zeta

potential value decreased towards acidic pH values.

3.2. Adsorptive fouling of NF membranes

Adsorptive fouling which represents membrane–solute

interactions without flux through the membrane was

experiments.

jection Sucrose rejection(%)c

Glucose rejection(%)c

Contact angle(�)d

98 73 40.1� 1.8

99 98 44.6� 4.9

rejection based on conductivity measurement.

glucose rejection based on TOC measurement.

-19

-17

-15

-13

-11

-9

-7

-53 4 5 6 7 8 9 10

pH

Zeta p

oten

tial (m

v)

TFC-SR3TFC-SR2

Fig. 3 – Zeta potential of the two NF membranes as function

of pH value.

Table 4 – Effect of ionic strength on rejection of cephalexinby the two NF membranes and the related permeatefluxes (transmembrane pressure 10 bar, pH [ 7.5; initialconcentration of cephalexin 500 mg/L).

Membrane/ionicstrength

No alginate 25 mg/L alginateadded

Rejection(%)a

Flux(L/m2 h)b

Rejection(%)a

Flux(L/m2 h)b

SR2 10 mM w100 50.4 w100 49.2

20 mM 91� 1 48.9 93� 1 48.4

SR3 10 mM 89� 1 23.1 86� 2 22.1

20 mM 93� 1 22.1 98� 3 21.2

a Average value� standard deviation.

b Steady state fluxes after 2 h filtration.

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 0 3275

investigated by exposing the outer membrane surface to the

drug solution. In addition, the effect of alginate on that

adsorptive fouling was also investigated. The relative water

flux reduction (RFR) was used to identify these membrane–

solute interactions. The results showed that no change in

water flux was observed after exposing the two membranes to

drug solutions for all types of pharmaceuticals (acetamino-

phen, tetracycline, cephalexin, indomethacin and amoxi-

cillin). Furthermore, the addition of alginate into the

tetracycline solution yielded the same result.

3.3. Cross-flow nanofiltration

3.3.1. Effect of pH on drug rejection and permeate fluxTo investigate the effect of pH on rejection and permeate flux

of membranes, experiments were performed with feed solu-

tions at different pH values (6, 7.5 and 9). In this study, acet-

aminophen, with the lowest molar mass among the five drugs

and a phenolic group, was used. Because of this phenolic

group, the properties of this PhAC are expected to be sensitive

0

10

20

30

40

50

60

70

80

5 6 7 8 9 10pH

Flu

x (L

/m

2h

)

0

10

20

30

40

50

60

70

Rejectio

n (%

)

flux-SR2 flux-SR3 Rej-SR2 Rej-SR3

Fig. 4 – Influence of pH on acetaminophen rejection and

permeate flux (the feed solution contained 500 mg/L

acetaminophen and 10 mM NaCl).

to the pH value. Fig. 4 shows the effect of solution pH on

acetaminophen rejection and permeate flux. It was observed

that for both NF membranes, as the pH was increased the

permeate flux and solute rejection would also increase.

3.3.2. Effect of ionic strength on drug rejection andpermeate fluxTo study the effect of ionic strength on rejection and permeate

flux of membranes, the salt content of the feed solution was

adjusted with NaCl (10 and 20 mM). In this study, cephalexin,

with medium molar mass and amino and carboxylic acid

groups, was used. It is expected that with such structure the

effect of ionic strength will clearly be observed (in fact,

amoxicillin can also be used for this purpose). In addition, the

effect of addition of alginate was also investigated. Table 4

shows the rejection of cephalexin and the permeate fluxes for

the two membranes. For membrane SR2, increasing the ionic

strength of the feed solution decreased the rejection of

cephalexin. By contrast, for membrane SR3 the rejection

increased as the ionic strength was increased. The presence of

alginate in the cephalexin solution slightly increased the drug

rejection at higher ionic strength while at lower ionic strength

almost no change was observed.

0

10

20

30

40

50

60

70

80

90

100

5.0 7.5 10.0 12.5 15.0Transmembrane pressure (bar)

Flu

x (L

/m

2h

)

50

60

70

80

90

100

110

Rejectio

n (%

)

flux-SR2 flux-SR3 Rej-SR2 Rej-SR3

Fig. 5 – Influence of transmembrane pressure on

tetracycline rejection and permeate flux (the feed solution

contained 500 mg/L tetracycline; pH [ 7.5, 10 mM NaCl).

22

23

24

25

26

27

28

29

30

31

32

0 40 80 120 160 200 240 280 320 360 400Time (min)

Flu

x (L

/m

2h

)

Added alginate, therebythe concentration of

alginate was 25 mg/L Added alginate, thereby the concentration of

alginate was 50 mg/L

AcetaminophenAmoxicillin

CephalexinIndometacin

Tetracyline

Fig. 7 – Influence of NOM alginate on permeate flux of

nanofiltration membrane SR3 (transmembrane pressure

10 bar, pH [ 7.5, feed concentration of pharmaceutical

500 mg/L).

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 03276

3.3.3. Effect of transmembrane pressure on the drug rejectionand permeate fluxTo investigate the influence of transmembrane pressure on

performance of the membranes, experiments were performed

at 7.5, 10 and 12 bar. In this study, tetracycline, the largest

among the five drugs, was used. Regardless the mechanism of

separation, with this high molar mass, it is expected that the

effect of pressure will obviously be observed. Fig. 5 shows the

rejection of tetracycline and the permeate flux at different

transmembrane pressures for the two membranes. It is seen

that the rejection of tetracycline increased with increasing

transmembrane pressure for membrane SR2. For membrane

SR3, the rejection showed a plateau value in the range of

95–98%. The permeate flux increased with increasing trans-

membrane pressure for both membranes. These findings are

in accordance with the results of other previous studies (Tang

et al., 2007). They indicated that the (initial) fluxes of

membranes varied almost linearly with applied pressure.

Nevertheless, different trends were observed for long-term

filtration. Overall, the influence of pressure on performance

for membrane SR2 was more pronounced than for SR3.

3.3.4. Effect of polymeric organic matter on the rejection andpermeate flux behaviorEffect of polymeric NOM was investigated by introducing

alginate at two different concentrations (25 and 50 mg/L) into

the drug solutions. In this study, all five PhACs were used.

Figs. 6 and 7 show the influence of polymeric NOM alginate on

permeate flux behavior for membranes SR2 and SR3, respec-

tively. Initially, filtration was performed without addition of

alginate for 2 h. Thereafter, alginate was added in order to

obtain drug solution with concentration of alginate of 25 mg/L.

After 2 h filtration, the alginate was further added so that the

concentration became 50 mg/L. It was observed that the

addition of alginate decreased the permeate flux for both NF

membranes. However, the decrease in flux after addition of

alginate was more pronounced for NF membranes having

higher permeability (SR2). The permeate flux was further

decreased after addition alginate for the second time. In

40

45

50

55

60

65

70

75

80

85

0 40 80 120 160 200 240 280 320 360 400Time (min)

Flu

x (L

/m

2h

)

AcetaminophenAmoxicillinCephalexinIndometacinTetracyline

Added alginate, thereby the concentration of

alginate was 25 mg/L

Added alginate, therebythe concentration of

alginate was 50 mg/L

Fig. 6 – Influence of NOM alginate on permeate flux of

nanofiltration membrane SR2 (transmembrane pressure

10 bar, pH [ 7.5, feed concentration of pharmaceutical

500 mg/L).

addition, it was generally observed that the flux decreased

over filtration time.

Tables 5 and 6 show the influence of alginate concentration

on rejection of the PhACs for the membranes SR2 and SR3,

respectively. In the absence of alginate, in line with the initial

characterizations (cf. Tables 1 and 3), membrane SR3 generally

gave much higher rejections for four drugs than membrane

SR2. However, the reverse order for cephelexin was unex-

pected. For both membranes, the lowest rejections were

observed for the smallest drug acetaminophen. For membrane

SR2, significant deviations from size-based separation were

observed for amoxicillin (lower rejection than other drugs with

similar size) and cephalexin (higher rejection than other drugs

with similar size). Further, it was observed that the presence of

alginate in the solutions increased in some cases the drug

rejection, and this effect was more pronounced with

increasing alginate concentration. For membrane SR2, major

increases in rejection were only observed for indomethacin

and tetracycline. A clear exception was the smallest drug

acetaminophen, where a decrease of rejection was observed

for membrane SR3 (decrease in rejection for membrane SR2

was within the range of standard deviation).

Table 5 – Effect of alginate on drug rejection for NFmembrane SR2 (transmembrane pressure 10 bar,pH [ 7.5, feed concentration 500 mg/L, 10 mM NaCl).

Drug Noalginate

25 mg/Lalginate

50 mg/Lalginate

Acetaminophen 34� 2 32� 2 30� 1

Amoxicillin 64.9� 1 64� 1 62� 3

Cephalexin w100 w100 w100

Indomethacin 82� 1 85� 1 95� 1

Tetracycline 89� 5 94� 1 97� 1

Table 6 – Effect of alginate on drug rejection for NFmembrane SR3 (transmembrane pressure 10 bar,pH [ 7.5, feed concentration 500 mg/L, 10 mM NaCl).

Drug Noalginate

25 mg/Lalginate

50 mg/Lalginate

Acetaminophen 58� 1 53� 2 49� 2

Amoxicillin 95� 2 98� 1 99� 1

Cephalexin 88� 1 86� 2 78� 2

Indomethacin 95� 5 98� 2 w100

Tetracycline 98� 1 w100 w100

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 0 3277

4. Discussion

4.1. Membrane characterization

Considering hydraulic permeability and rejection data of both

membranes SR2 and SR3 (Table 3), a trade-off between flux and

rejection was apparently observed. However, in contrast to data

for NaCl, for the charged solute from bivalent ions, MgSO4, the

difference in rejection was not significant. Similar phenomenon

was observed for non-charged solutes: a significantly different

rejection was only observed for the smaller solute, glucose, but

not for the larger solute, sucrose. Compared to membrane SR3,

membrane SR2 had similar rejection of bivalent salt but

significantly lower rejection for glucose. This implies that the

effect of charge interactions (Donnan exclusion) on separation

was significantly larger for the membrane SR2 (cf. Baker, 2004).

In general, the permeability and solute rejection results

obtained in this work agree well with the membrane charac-

teristics given by the manufacturer (cf. Table 1).

Characterization of membrane surface chemistry by ATR-

IR spectroscopy suggests that both membranes are made from

similar material. Specific bands indicate that the base

membrane was made from an aromatic sulfone polymer; and

due to the penetration depth of the ATR method, w2 mm, it is

possible to detect the base polymer underneath the thin active

layer of the composite membrane. The other bands in the IR

spectra are in agreement with a polyamide structure of the

active layer, but more detailed assignments could not be

made. The difference in peak intensity in certain band areas

(cf. Section 3.1) can be explained by different contact area with

the crystal during the ATR measurement. Although ATR-IR

spectra indicated that both membranes were made from the

same material, CA measurements showed different values.

The most probable reason for this difference is that the degree

of swelling of the active layer of membrane SR2 was higher

than of SR3 but its swollen thickness was smaller as noticed

by its higher hydraulic permeability and lower solute rejection

(cf. Table 3). This explanation is supported by previous studies

by Freger (2003, 2004) who measured the swelling degree of

the thin active layer of different polyamide composite NF and

RO membranes. It was reported that with the same swelling

degree, NF membranes could have different hydraulic

permeability because their active layer thickness was

different. The thinner the active layer, the higher hydraulic

permeability was observed. Further, his results also showed

that there was a correlation between the changes in the active

layer swelling and permeability (Freger, 2004).

As presented in Fig. 3, the membranes have a negative

surface charge which is decreasing towards acidic pH values.

This phenomenon can be due to the dissociation of membrane

functional groups such as carboxylic acid, and adsorption of

hydroxyl ions to the membrane surface. Qualitatively, both

effects will be influenced by the pH of the solution in the same

way. Charge interaction between fixed ionic groups on the

membrane surface can modify the effective membrane pore

size to some extent (Childress and Elimelech, 2000). Overall,

the surface charge of the membrane SR3 seemed to be

somewhat larger than for SR2. This would be in contrast to the

description of the barrier effects where a larger Donnan effect

was ascribed to the membrane SR2 (cf. above). However, when

considering the wettability and the flux data and the related

interpretations (cf. above), the lower surface charge density of

membrane SR2 can be related to its higher degree of barrier

layer swelling at a lower barrier thickness than for membrane

SR3.

4.2. Nanofiltration separation performance andmechanism

The results obtained from adsorption experiments suggest that

the effects of pure adsorptive fouling during removal of PhACs,

even in the presence of polymeric NOM were negligible. In

particular for NOM, this is different from results for UF

membranes (Susanto and Ulbricht, 2005, 2008; Susanto et al.,

2007). However, it can be well understood because the hydraulic

resistance of a molecular monolayer, even of the polymer

alginate, is much smaller than the resistance of the polyamide

barrier layer of the NF composite membrane.

Flux behavior as well as rejection profile during NF is

significantly affected by the pH and the ionic composition of

the drug solution. In addition, transmembrane pressure and

NOM content also influence such behavior. Both permeate flux

and solute rejection increased with increasing pH value of the

solution (cf. Fig. 4). The possible explanation for this observa-

tion is that the membrane charge would be more negative due

to deprotonation of carboxylic acid groups under alkaline

conditions. At the same time (when moving to higher pH), the

phenolic group of acetaminophen would be deprotonated

leading to more negatively charged character of the solute.

Under these conditions, the electrostatic repulsion between

acetaminophen and membrane will be larger leading to larger

rejection. The slightly reduced permeate flux (mainly water)

with decreasing pH is related to the rejection behavior. At lower

pH the electrostatic repulsion would be less significant than at

higher pH, consequently, concentration polarization on the

membrane surface, which reduces the flux, would be more

significant. Similar trends of decrease in permeate flux with

decreasing pH solution were also observed in other reports (Lee

et al., 2006; Liikanen et al., 2005).

In contrast to the effect of solution pH value, the effects of

ionic strength on permeate flux and solute rejection were

dependent on the membrane itself (cf. Table 4). Decreasing

rejection with increasing ionic strength observed for

membrane SR2 can be explained as follows: both the charge of

the solute and the membrane are reduced due to double layer

compression, leading to a decrease in electrostatic repulsion

between the cephalexin and active layer of the membrane.

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 03278

Nevertheless, this explanation is not valid for membrane SR3,

which showed a slight increase in rejection with increasing

ionic strength. This indicates that the drug separation mech-

anism is different for both membranes. Indeed, much

stronger influence of Donnan exclusion on rejection has been

evoked for membrane SR2 than for membrane SR3 (cf. Section

4.1). Such difference in transport mechanism for different NF

membranes was also found by Nghiem et al. (2005). They

reported that the retention of pharmaceuticals by a tight NF

membrane is dominated by steric exclusion, whereas both

electrostatic repulsion and steric exclusion govern the reten-

tion of ionizable pharmaceuticals by a loose NF membrane.

This is fully in line with our results and interpretation.

The permeate flux and rejection trends as function of

transmembrane pressure up to 12.5 bar (cf. Fig. 5) suggest that

the separation mechanism of both membranes is different. For

membrane SR2, the separation is not mainly determined by

size exclusion mechanism. It should be noted that size exclu-

sion separation typically shows a trade-off between permeate

flux and rejection. Nevertheless, considering the trends of the

rejection data, constant or decreasing rejection would probably

be observed with further increase of transmembrane pressure.

For membrane SR3, an indication of size exclusion mechanism

can more obviously be observed than for membrane SR2.

The observed trend in rejection cannot be explained with

the (large) differences in the log P values (cf. Table 2). There-

fore, charge effects would have larger impact which is in

agreement with the properties of this membrane (cf. Section

3.1). However, the pK values (both, amoxicillin and cepha-

lexin, have one amino and one carboxylic acid; the phenolic

group of amoxicillin should be protonated at pH 7.5) cannot

also provide a convincing explanation for the large differences

in rejection. In contrast, for membrane SR3, rejections are

mainly governed by size exclusion. This is in agreement with

the results obtained from the effect of transmembrane pres-

sure (cf. above).

4.3. Influence of alginate on nanofiltration separationperformance

Because polymeric NOM used in this work is completely

retained by the membrane, it will form a fouling layer on the

membrane surface and thus increase the permeate flow

resistance. As a result, decreasing permeate flux in the pres-

ence of polymeric NOM was observed. This explanation is

supported by further decrease in permeate flux if the

concentration of polymeric NOM added was increased (cf.

Figs. 6 and 7).

A different effect of ionic strength was observed in the

presence of the NOM alginate (cf. Table 4). In this case, algi-

nate could slightly hinder penetration of drug into membrane

active layer when the higher salt concentration lead to a more

compact adsorbed NOM layer. Slight increase in rejection in

the presence of NOM was also observed during NF of PhACs

dissolved in treated surface water (Verliefde et al., 2008). On

the other hand, no significant effects of ionic strength and

alginate on permeate flux (mainly water) were observed for

both membranes.

Except for acetaminophen and cephalexin with

membrane SR3, addition of alginate increased drug rejection

(cf. Tables 5 and 6). With its moderate log P, acetaminophen

would be enriched on/in the polar alginate layer and more

easily diffuse through the membrane barrier to the permeate

side, thus decreasing the observed rejection. This explana-

tion is also valid for cephalexin, which has lower log P.

Nevertheless, such phenomena were not found for

membrane SR2 due to its much smaller membrane resistance

compared to SR3 (note that, SR2 has higher hydraulic

permeability and consequently the effect of solute diffusion

should be smaller). The major increase in rejection for

indometachin and tetracycline in the presence of alginate for

membrane SR2 can be explained because the alginate fouling

layer could not only provide charge repulsion between

carboxylic acid groups of the drug and of the alginate but

could also contribute to the size exclusion. For membrane

SR3, all changes (except for acetaminophen; cf. above) were

quite small, and this can be related to the fact that this

membrane is significantly tighter than the membrane SR2 (cf.

Tables 1 and 3).

5. Conclusions

In this study, the removal efficiency for five pharmaceuticals

by two commercial NF membranes was investigated with the

aim to study also the effect of polymeric NOM (here alginate

as model) on the separation performance. No water flux

reduction due to adsorptive fouling was observed, but the

addition of alginate during nanofiltration lead to significantly

reduced permeate fluxes, i.e. membrane fouling. Overall, the

rejection efficiency of membrane SR3 was higher than of

membrane SR2 what was in line with rejection data for

standard test substances and water flux data. The PhACs

rejection and permeate fluxes were influenced by pH, ionic

strength, and transmembrane pressure, and those effects

were a function of structure and property of the PhACs and

properties of the membrane. Both size exclusion and

Donnan exclusion contributed to the separation; the effect of

Donnan exlusion was much more pronounced for the

membrane SR2 which has higher flux and surface hydro-

philicity (both presumably due to larger swelling of the

active polyamide layer) than membrane SR3. Addition of

alginate to the feed significantly influenced drug rejection

and permeate flux. Again, the changes were a function of the

pharmaceutical: for the smallest substance with moderate

polarity a decrease of rejection due to the alginate fouling

layer was observed; for large drugs or drugs with the same

charge as the fouling layer, an increase of rejection was

observed. In conclusion, this study demonstrates the high

potential of NF for the removal of pharmaceuticals from

aqueous streams but it emphasizes also that the additional

effects of membrane fouling on removal efficiency must be

considered.

Acknowledgements

One of the authors (MAZ) is grateful for the financial support

of his stay at Universitat Duisburg-Essen (UDE) by Tehran

w a t e r r e s e a r c h 4 3 ( 2 0 0 9 ) 3 2 7 0 – 3 2 8 0 3279

University of Medical Sciences. The authors thank Marcel

Gawenda (UDE) for his help to prepare the NF set-up, Inge

Danielzik (UDE) for her contribution to the HPLC analysis and

Claudia Schenk (UDE) for technical support. The donation of

the membranes by Dr. Hans-Werner Rosler, CUT GmbH &

CoKG, Erkrath, is gratefully acknowledged.

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