Desalination 315 (2013) 46–60

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Desalination

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Transmission of p-anisic acid through nanofiltration and goat membranes

Pankaj J. Gandhi, Z.V.P. Murthy ⁎Department of Chemical Engineering, S. V. National Institute of Technology, Surat — 395 007, Gujarat, India

H I G H L I G H T S

► p-Anisic acid transmission through NF membranes is reported for the first time.► This study provides useful information for product development in medical science.► It gives an idea on local drug delivery in dermal and post breast cancer treatments.► Transmission is affected by pressure, temperature, and feed flow rate.

⁎ Corresponding author. Tel.: +91 261 2201641, +92227334.

E-mail addresses: zvpm2000@yahoo.com, zvpm@ch

0011-9164/$ – see front matter © 2012 Elsevier B.V. Allhttp://dx.doi.org/10.1016/j.desal.2012.09.002

a b s t r a c t

a r t i c l e i n f o

Article history:Received 11 May 2012Received in revised form 4 August 2012Accepted 2 September 2012Available online 26 September 2012

Keywords:p-Anisic acidNanoparticlesNanofiltrationGoat membraneZeta potentialMass transfer coefficient

The aim of this work was to study the transmission of p-anisic acid through two different membranes, viz.,commercially available nanofiltrationmembrane (NF-300) and a goatmembrane. The p-anisic acid is a crystallineorganic compound having vital applications in medical science for the treatment of Parkinson's disease, hepatitisB and C viruses, liver diseases, post radiation treatment of breast cancer, and skin desquamation. The study oftransmission (or rejection) of material and change in the permeate flux have been made with respect to changesin feed concentration, pH, cross flow velocity, time and temperature and found that the transmission of p-anisicacid is affected by the type of membrane, its pore size and structure of pores. Also a study pertaining to themasstransfer coefficient has beenmade and evaluated the samewith different theories. Mass transfer of p-anisic acidis explained in a better way by the simple graphical theory. The transmission of p-anisic acid is affected by themembrane structure and its type. A higher transmission was observed through the goat membrane. Usingnanosize particles the drug dosage can be reduced with better diffusion, further, toxicological aspects can alsobe reduced.

© 2012 Elsevier B.V. All rights reserved.

1. Introduction

Nanosize particles are gaining importance in various researchactivities and industries such as cosmetics, dyes, electronics, pharma-ceuticals and many more [1]. In pharmaceutical industry for activepharmaceutical ingredient (API), particles with less than 1 micron sizeare considered as nanoparticles [2]. Modern drug delivery systemshave realized the importance of nanosize particles for deriving betterresults [3]. Most of the newly developed drugs are poorly solublein water, and poor solubility results in low bioavailability or erraticabsorption of drugs [2–7].

The p-anisic acid, an organic compound, found naturally in anise is awhite crystalline solid, which is insoluble in water at room temperature,and soluble in alcohols, ether and ethyl acetate [8]. Improvement in drugsolubility makes them suitable for absorption in gastrointestinal tract

1 261 2201642; fax: +91 261

ed.svnit.ac.in (Z.V.P. Murthy).

rights reserved.

into the bloodstreamandhelps them reach the site of action [9]. Organicsolvents selectively adsorb to the specific faces of the crystal and suitablydissolve them. Ethanol was selected as the solvent due to its extensiveuse in pharmaceutical synthesis, good solubility of many organic solutesat high concentrations and easy availability. The p-anisic acid is beingwidely used as an aroma component in foodstuff [10], as a preservativein skincare products [10,11], and as a drug in dermatological applica-tions [12].

The p-anisic acid is having an antineurotoxic behavior, which isuseful for developing drug formulation for addressing Parkinson's dis-ease [13,14]. Gadgoli and Mishra [15] have evaluated antihepatotoxicactivity of p-anisic acid which is quite useful for addressing the diseasescaused by hepatitis B and hepatitis C viruses and also in the diseaseswhere liver can be damaged by infections. Recent use of Food andDrug Administration (FDA) approvedmedicines for curing HIV infectedpatients have shown hepatotoxic behavior and results into damage ofthe liver [16,17]. It is estimated that across the globe, more than 90%of breast cancer patients treated with radiotherapy suffer from radia-tion dermatitis [18]. Based on the published results [19–25], it hasbeen found that therapeutic doses of radiation results into persistentskin erythema, dry desquamation, moist desquamation rash, pain,

47P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

itching and ulceration. Across the globe there is no evidence based op-timal treatment for radiation dermatitis [26]. Cotton and Amar [12]found that p-anisic acid can effectively be used for addressing the des-quamation and stimulating epidermal renewal. After the experimentson rat, Cramer and Michael [27] noted that there are no toxic effectsdue to the hydrolysis of p-anisic acid, and also found that p-anisic acidwas rapidlymetabolized and excreted from the body. So, it is of interestto understand the transmission behavior of p-anisic acidwithin the skincells or tissue membranes.

Based on the above discussion, it can be said that it is appropriate tostudy the penetration of chemicals, drugs and other similar pharmaceu-tical substances through skin, membrane and biological barriers withthe help of in-vitro testing [28,29]. In view of the developments ofnew pharmaceutical formulations and assessment of risk associatedwith the same, a study of permeability of substances through mem-branes is important in today's era [30]. Skin is one of the biggest andcomplicated multilayer organs in human body and is widely used formeeting the transdermal drug delivery applications [31]. For the de-velopment of various pharmaceutical products and ointments for de-livering them through transdermal route for the diseases pertainingto the skin, cancer and other similar diseases in-vitro skin transportstudies provide valuable information for designing a final product[28].

Stamatialis et al. [31] gave a detailed usage ofmembranes inmedicalapplications, mainly in the drug delivery systems through diffusionmechanisms. The usage of artificial and natural membranes in medicalfield has been increased in the last decade [31,32]. Some of the featuresofmembranes, such as specific pore sizes, narrowpore size distributions,high porosity, high diffusion coefficients, smooth surfaces and thin skinlayers make them suitable for meeting the medical science applications[33–35]. The drug release in diffusion basedmembrane system ismainlycontrolled by transport mechanism of the drug across the membrane[31]. The transport mechanism of the drug across the membrane isgoverned by the Fick's law of diffusion and is influenced by the drug dif-fusivity,membrane type andmembrane thickness [31].With thehelp ofpredictive methods, drug transmission through membrane is deter-mined [31,36]. Presence of polymeric materials on to a surface of mem-brane pores develops transmission switches and gates [31], thesepolymeric materials are affected by the changes in the average particlesize, time, concentration, temperature and pH, which in turn affect theperformance of the membrane systems [37–43]. In a membrane basedsystem, drug release is influenced by the feed concentration, pH of thefeed, and drug transmission through membrane [31].

Shulka and Mishra [44] have studied the effect of pressure changeacross the urinary bladder membrane and found that a membrane'spermeability is influenced by the molecular size, pores, physiologicalstate, density and viscosity of permeate, solubility of permeate andnumber of hydrogen bonds. Kermis et al. [45] have developed cross-linked pHEMA membranes and studied the permeation of creatinineand IgG-Fab fragment for meeting the transdermal and dialysis re-quirements and stated that the permeation of substances is con-trolled by a Fick's law of diffusion. Liu et al. [46] have found thatPLGA/collagen membrane can be effectively used in the treatment ofwound dressing.

Even though animal skins are not revealing the drug transport dataequivalently with human skin [47] they are used by the researchers toknow the drug permeation behavior through the skin due to the restric-tion on the use of human skin in some countries [30,47]. Also the use ofartificial polymericmembranes has been increased in the past fewyearsfor simulating the skin's permeation behavior through in-vitro ex-periments [30,47–50]. The skins are having lipophilic and hydrophilicpathways [47,49,51–57] whereas the synthetically derived polymericmembranes have micro channels of pores which mimic the lipophilicand hydrophilic domains [30,47]. The drug transport takes placethrough these lipophilic and hydrophilic pathways, which comprisenanopores. Porosity is one of the important characteristics ofmembranes

and the efficiency of the membrane is dependent on it [58]. In NF, themechanism of separation depends on the factors such as electric repul-sion, particle size, etc. [59]. Zhang andWu [60] have examined the effectof temperature and pH on transmission of nanoparticles of various pep-tides, proteins, and vitamin B12. Urase and Sato [61] have studied the be-havior of different types of nanofiltration (NF) membranes for selectedpharmaceuticals with respect to changes in pH. Chandrasekran et al.[62] have explained the different types of therapeutic systems whichare utilizing membrane controlled diffusion mechanism for delivering adrug through local drug delivery systems, such as intrauterine progester-one contraceptive system, ocular therapeutic system, and transdermaltherapeutic system. During the last decade, in the pharmaceutical in-dustry, usage of pressure driven nanofiltrationmembranes has been in-creased to a great extent [63] mainly in the area of antibiotics [64,65],such as tylosin [66], fermentation broths [67] and pharmaceutical prod-ucts such as erythromycin [68] and amoxicillin [63].

Themain objective of the present work was to investigate the trans-mission of p-anisic acid through a natural membrane obtained fromgoat's internal skin and compared it with thin film composite polyamidenanofiltration membrane (NF-300 membrane, Permionics, Vadodara,India) as a function of various parameters, such as time, concentration,temperature and pH. It was presumed that membranes used here actas human skin cell or tissue and the experimentation enables better un-derstanding of the system which could serve as novel dermal carrierswith controlled release kinetics and targeted drug delivery through theskin membrane in humans for meeting the various medical require-ments. To our knowledge, this will be the first report to study the trans-mission or rejection of p-anisic acid through asymmetric imprintedmembrane and asymmetric natural membrane. The present researchwork is helpful to understand the separation effect and recognitionphenomenon in aqueous media. Also this study will provide the direc-tion for the selection of asymmetric polymeric and natural membranesas selective absorbent or separation routes for drug purification andseparation of drug isomers. Anisic acid exhibits in ortho-, meta- andpara-isomer form. Here an attempt has been made to provide thebasic information pertaining to the addressing of the purification andenvironmental issues, however there is further work required toestablish the physical relationships and process parameters.

2. Materials and methods

2.1. Membranes

Two membranes, viz., (i) NF 300 (Permionics, Vadodara, India)which is a thin film composite nanofiltration membrane having a mo-lecular weight cut-off (MWCO) of 300 Da, and (ii) naturally extractedgoat skin parchment membrane with the help of a local slaughterhouse having pore sizes of around 46 nm (varying due to the naturalcharacteristics) suited for nanofiltration experiments. The pore radiuswas determined with the help of stearic-hindrance pore (SHP) model[69]. The internal layer of the goat skin membrane obtained was firstwashed with water, and then soaked in 0.7% NaCl solution [44] for3 h. After that the skin was removed from the brine solution andwas treated with 10% formalin-alcohol solution [46] according tothe procedure explained elsewhere [70–73] to remove debris, fatsand preservatives; and was then dried in an oven, and processedthrough rollers to obtain a perfect flat sheet. Both the membranesused for the experimentation were flat sheet membranes and werestored in a 4% formalin solution at 5 °C.

2.2. Chemicals

The p-anisic acid (MW=152.15 g/mol, 99% purity) used was de-rived according to mWE reaction, details of the method has beenreported elsewhere [74], and reduced its average particle size to250 nm through the sonicationmethod [75]. Surfactant (biodegradable

48 P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

Tomadol 23–6.5)was provided by Air Products Asia Inc., Singapore, anddistilled water of pH 5.9±0.2 and conductivity of 1.0 μS/cm (Millipore,India) were used as water media in all the experiments. Hydrochloricacid (Merck, India), sodium hydroxide (Merck, India), sodium chloride(Finar Chemicals, India), ethanol (Finar Chemicals, India) and citric acid(Finar Chemicals, India) were used in the experiments to adjust the pHand for cleaning purpose.

2.3. Analytical methods

A Shimadzu HPLC system equipped with Supelco drug discoveryC-18 column (with diameter, length and pore size of 4.6 mm, 250 mmand 5 μm, respectively) and a UV spectrophotometer detector (HACHDR-5000) was used to analyze p-anisic acid concentration in feed andpermeate samples. The same procedure as reported in our previouswork [74] was followed to measure p-anisic acid concentration. Micro-processor based pH system (1012 E, Swastik, India) was used to mea-sure pH at various stages during the experiments.

2.4. Determination of particle size and distribution

Average particle sizes of p-anisic acid were measured after thesonication process onMalvern Zetasizer, Model # ZS 90 (Malvern Instru-ments, UK). For particle sizemeasurements, on zetasizer, the parameterswere set as follows: material RI (refractive index)=1.59; dispersionRI=1.33; material absorption=0.01; dispersion name=water;temperature=25 °C; scattering angle=90o, measurement posi-tion=4.65 mm; and viscosity=0.8872 cP. Size measurementswere made using disposable polystyrene cells. TheMalvern Zetasizerprovides data of average size (Z average) of particles in nanometerwith its size distribution.

2.5. Infrared spectroscopic analysis

FTIR study was carried out for both the membranes on an FTIRspectrometer (Model 8400S, FTIR INS Shimadzu). All the FTIR wereperformed in transmission mode with a wave number region of4000–400 cm−1. FTIR analysis has been made for both the mem-branes for identifying different constituents, mainly the presence ofactive surface functional groups.

2.6. Surface morphology and characteristics

For having an idea of surface properties of themembrane, its pore sizeand other such relevant information, we have performed the scanningelectron microscopy (Model # LEOs-440i, Leo Electron Microscopy,Cambridge, UK and Model S-3400N, Hitachi, Japan) to characterizemembrane surfaces. SEM images of membrane surfaces and theircross-sections were taken. SEM images of membranes were obtainedfor pre-and-post filtrations.

The surface charge (apparent zeta potential) of the membranes wasanalyzed because it is useful to understand the fouling behavior of themembrane [76,77] and to describe the material rejection by nano-filtration qualitatively. The zeta potential (ξ) of membranes was ana-lyzed along the surfaces since the membranes studied are flat andtight and do not allow for a free passage of the electrolyte through themembrane. The ξ of both the membranes were determined using astreaming potential analyzer (Model # ECO 780 SP, M/s. Veer Instru-ments, Bharuch, India) according to the procedure explained elsewhere[76,78]. The calculation of the charge density of the membrane surfaceand pores was done by performing titration measurement of syntheticmembrane and goat membrane material and by streaming potentialmeasurement of the nanofiltration membrane. The ξ was calculatedfrom the Helmholtz–Schmoluchowski equation [78] without any cor-rections, which represents the value of apparent zeta potential. Herethe value of ξ represents the surface charge and provides comparable

values. The streaming potential, developed by the flow of 1 mMKCl-solution at 25 °C in a slit (height about 0.5 mm) of two membranesheets, is linear to pressure drop across the slit. The slope of this linewas determined and the zeta potential calculated accordingly fromHelmholtz–Schmoluchowski equation. Samples of both themembraneswere first cut as per the desired size, and then they were cleaned in anultrasonic bath in 150 mL of Millipore water for three times. Thecleaning cycle comprises 12 min and in each cycle fresh water wasused. After water cleaning, in separate beakers, the membranes weresoaked in 20% ethanol for 15 min for wetting of the surfaces and thensamples were washed with water.

2.7. Laboratory scale NF test cell

A laboratory scale Perma®-pilot membrane system (Permionics,Vadodara, India) filtration test unit was used to carry out the NF exper-iments. The membrane housing cell is made of stainless steel (SS 316)(240 mm [L]×180 mm [W]×25 mm thickness) with two halvesfastened together with bolts. The top half of the cell contained theflow distribution chamber and the bottom half was used as themembrane support system along with the passage of permeates.The effective surface area for themembranewas150 cm2. Toprovide suf-ficient mechanical support to the test membrane Whatman filter paperwas laid over the perforated stainless steel gauge. To avoid leakage, theupper half of the test cell was equipped with ‘O’ ring boundary of thegasket material. Experimental setup and details of the experimentationwere given elsewhere [79–81].

2.8. Nanofiltration experiments

Prior to experiments, the membrane was conditioned by filtratingdistilled water to reach the maximum permeability coefficient of themembrane. In order to avoid membrane compaction the membranewas stabilized for 4 h at 10 bar until therewas no variation in the perme-ateflux. The feed temperaturewas kept constant at 30±1 °C throughoutthe experiments, except when experimental results as a function of tem-perature were to be obtained. The purpose of carrying the experimentsat 30 °C is to know the performance of the membrane (mainly the syn-theticmembrane) in terms of transmission and fluxwhichmay be usefulfor the environmentalist in effluent treatment, which is also useful inthe drug purification and in the separation of isomers. Traditional ef-fluent treatment for p-anisic acid (aromatic ring structure) con-sumes more energy and time; whereas such type of syntheticmembrane based treatment will help them to recover the materials,as well as it will reduce the cost and time of treatment. Initially thewhole set-up was run for 1–2 h to stabilize the system. After theabove stabilization process, pure water permeability (PWP) was mea-sured at different pressures starting from high pressure to low pressureusing Millipore water. The experiments were performed in cross-flowbatch circulation mode and hence permeate and concentrate wererecycled to the feed vessel in order to keep the feed concentration con-stant. The experiments were carried out at different feed concentra-tions of p-anisic acid (50, 100, 150, 200, 250, 300 mg/L), appliedpressure (4, 6 bar), time (0.5, 1, 1.5, 2, 2.5, 3 h), temperature (36,37, 38, 39, 40 °C) and pHs (3, 4, 5, 6, 7) for both NF-300 and thegoat membranes. The feed solution was prepared by first dissolvinga required amount of p-anisic acid in ethanol (for 1 mg of p-anisicacid 3 mL of ethanol was taken) and then homogenized it inMillipore water. The corresponding permeate flux (Jv) was calculat-ed as the volume of permeate passed through the membrane perunit effective membrane area, per unit time in L/m2h for each set of op-erating conditions. The samples of feed and permeate were collected foreach set of operating parameters for analysis.

After each set of experiments for a given experimentation condition,the set-up was rinsedwith dilute citric acid solution for 45 min at 2 barto clean the system. This procedure was followed by a measurement of

49P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

PWP to ensure that initial membrane PWP is restored. The percentagetransmission of solute (T%) or observed rejection (Robs) was calculatedusing the following equations:

T %ð Þ ¼ Cp

Cf� 100 or Robs ¼ 1−

Cp

Cfð1Þ

where, Cp and Cf are the solute concentration in the permeate and feed,respectively.

2.9. Membrane transport model

2.9.1. Concentration polarizationAccording to the irreversible thermodynamics, the membrane is

considered as a black box [82]. The rejection of the solute by themembrane and its concentration near themembrane surface are relatedwith each other, the higher the concentration, the higher the rejectionof the solute materials by the membrane. The increment of the concen-tration at themembrane–liquid interface is termed as concentrationpo-larization [83].

2.9.2. TheoryThe concentration polarization is explained with the help of the

film theory and characterized on the basis of the Spiegler–Kedemmembrane transport model [82–84]. Due to the presence of concen-tration polarization, Eq. (1) is not providing the accurate results formembrane true or real rejection (R) and is to be changed as follows:

R ¼ 1−Cp

Cwð2Þ

where Cw is the solute concentration at themembranewall in upstreamside, whichwill be higher than the Cf. A mass balance of solute in differ-ential element can be explained with the help of boundary condi-tions [85]:

expJvk

� �¼ Cw−Cp

Cf−Cpð3Þ

where, Jv is volumetric flux through the membrane, k is mass transfercoefficient in the polarized boundary layer [86]. The above Eq. (3) rep-resents the mass transfer effect in exponential terms, which showsthat when concentration polarization is not there, Cw and Cf are equaland the exponential term becomes unity. In the presence of concentra-tion polarization at the membrane surface, Cw will be higher than the Cfand exponential becomes greater than unity. To derive the mass transfercoefficient from experimental data, Eq. (3) can be linearized as follows[85,87]:

ln1−Robs

Robs

� �¼ ln

1−RR

� �þ Jv

k: ð4Þ

Here, the mass transfer coefficient can be expressed as

k ¼ aun ð5Þ

where a and n are constants and u is the membrane cross flow velocity.Extrapolation of observed rejection data can derive the value of true re-jectionwith respect to infinite crossflowvelocity. A slope value of a bestfitted line in a graph of ln[(1−Robs)/Robs] versus Jv/un will provide avalue of 1/a. Rearrangement of Eq. (4) will provide the value of real re-jection as:

R ¼ 1

exp ln 1−RobsRobs

��� ���− Jvaun

h iþ 1

: ð6Þ

3. Results and discussion

3.1. Membrane characterization

3.1.1. FTIR analysis of the goat membraneFTIR analysis of the goat membrane (Fig. 1A) has been made to

determine the functional groups of the membrane. Details of variousgroups present in the membrane are mentioned in Table 1.

3.1.2. FTIR analysis of the NF-300 membraneFTIR analysis of the NF-300 membrane (Fig. 1B) has been made to

determine the functional groups of the membrane. Details of variousgroups present in the membrane are given in Table 2.

After comparing the FTIR analysis of both the membranes, it can besaid that almost similar bends of chemical compositions are havingtheir presence in both themembrane structures leading to a conclusionof similar functionality when they are exposed to the membrane sepa-ration process.

3.2. SEM images and surface analysis of membranes

3.2.1. SEM analysis of the NF-300 membraneFig. 2 comprises the top surface and cross sectional views of NF-300

membrane at differentmagnifications. The NF-300membrane is havingpores of different sizes with uniform distribution across the surfacewith fiber like polymeric material at the top side of the membrane.The roughness of the membrane surface was found around 13.2 nm(measured by atomic force microscopy measurement on a sample sizeof 2.5 μm by 2.5 μm). It is evident from the cross-sectional images(Fig. 2B,C,D) that the NF-300 membrane possesses an asymmetrictype imprinted structure, which consists of thin and dense layers, andsimilar observations were made by other researchers [88,89]. Thepores of the NF-300 membrane are completely covered by a thinimprinted layer (Fig. 2A). This fiber made of polymeric structure is ofpolyamide and is one of the active group members of the NF-300 mem-brane layer. The pore sizes were visualized under the cross-sections ofthe membrane. By looking at the cross-sections of the membrane(Fig. 2B,C) it can be said that the pore openings are clearly visible fromthe top side and from the cross-sectional view. The cross-sections ofthe membrane (Fig. 2B,C,D) indicate that the pores are cylindricalin nature and comprises various layers, also they indicate a large porouslayer having a finger-like void structure in the micron range, and adense porous layer with sponge-like structure pores. Fig. 2C indicatethe dense imprinted layer in NF-300 membrane; also Fig. 2D indicatesthe imprinted type half-cut cylindrical pores of the membrane.

3.2.2. SEM analysis of the goat membraneFig. 3 comprises the top surfaces and cross-sections of the goat

membrane at different magnifications. The goat membrane is having ahighly rough surface (Fig. 3A), of asymmetric type (Fig. 3C,D), andthere is no uniformity in pore distribution (Fig. 3B) as there is no porelike structure, with fiber like polymeric materials at the top side of themembrane. The roughness of the membrane surface was found to bearound 22.4 nm. The SEM images of the goatmembrane clearly indicatethat the membrane is having a fibrous structure and due to the samestructure the pathway of fluid in such type of membrane is followinga zigzag pattern [90]. This particular fibrous structure (Fig. 3B) is dueto the nature of skin collagen fibers and is one of the most importantparts of the membrane which induces effective adsorption of materialson the membrane surfaces [90]. It is evident from the cross-sectionalimages (Fig. 3C,D) that the goat membrane is having an asymmetricstructure, which consists of a dense layer of fibers like materials.

By comparing the SEM images of two different membranes (Figs. 2and 3), it can be said that the goat membrane is not having a porousstructure like that of the NF-300 membrane but it is having a meshlike structure comprising fibers which mimic the action to act as

4000.080.0

81828384858687888990919293949596979899

100.0

3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600 400.0

cm-1

4000.065.0

66

68

70

72

74

76

78

80

82

84

86

88

90

92

94

96

98

100.0

3600 3200 2800 2400 2000 1800 1600 1400 1200 1000 800 600 400.0

cm-1

%T

%T

3422.83

2923.33

2853.19

2588.832337.09

2085.45

1652.50

1558.10

1543.70

1510.16

1384.55

1315.291248.50

1121.281042.98

858.30

776.25

673.79 604.62

465.10

1410.86

1456.19

3426.19

2922.45

2853.04

2114.86

1741.64

1653.42

1574.961544.71

1461.05

1240.93

1340.57 1164.68

1202.86

1118.12

1081.061033.84

859.58

712.64671.16

469.47

A

B

Fig. 1. (A) FTIR spectrum of goat membrane; (B) FTIR spectrum of NF-300 membrane.

50 P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

pores. The cross sections of the membrane (Fig. 3C,D) indicate thatthere is the absence of pores and cylindrical structure; however, themembrane is having a dense structure of micro channels for thetransportation and diffusion of materials or drug particles. It hasbeen found that as compared to the polymeric NF-300 membrane,the goat membrane is having a higher mechanical strength as wellas it is convenient to handle due to the properties of leather [90].

3.3. PWP

Before the p-anisic acid transmission experiments, the PWP of themembrane using ultra pure water was measured at 30+1 °C. A plot ofPWP versus transmembrane pressure (TMP) gives a slope Lp, known asPWP coefficient of the membrane. The Lp value was found (figure notshown) to be 8.43 for the NF-300 membrane and 11.7 L/m2h bar forthe goat membrane, which were in the range of the NF membranes[91]. The Lp value was considered to be a reference to evaluate thecleaning procedure, concentration polarization and fouling nature ofthe membrane.

3.4. Effect of feed concentration and pressure as a function ofmembrane type

As it is known that nanofiltration is a pressure driven process,operating pressure is one of the critical parameters in the membranebased separation process. Fig. 4 indicates that the permeation fluxincreases with increasing pressure for both the NF-300 and goat mem-brane and for both the sizes of particles of p-anisic acid, and similar ob-servations have been noted in the literature [92,93]. Experiments withrespect to the pressure indicate that operating pressure has a remark-able effect on the membrane efficiency [63].

Experimentswere carried out at a constant temperature 30+1 °C tostudy the effect of feed concentrations ranging from 50 to 300 mg/L attransmembrane pressures of 4 and 6 bar. The effect of feed concentra-tion on the NF-300 and goat membrane is shown in Fig. 5. It can beseen that on increasing the feed concentration from 50 to 300 mg/L thetransmission of p-anisic acid increases. This was because in increasingthe feed concentration osmotic pressure increases (and so small drivingforce across themembrane) thereby decreasingwaterflux and increasingsolute permeability through the membrane [94]. From Fig. 4, it can besaid that as we increase the concentration of the feed the permeation

Table 1FTIR analysis of goat membrane.

Sr. no. Position of peakin FTIR graph

Type of vibration Presence of chemical groups

1. 3426.19 cm−1 N\H stretching Weak amides, primaryand secondary amines

2. 2922.45 cm−1 CH2 stretching Anti-symmetric type aromatics3. 2853.04 cm−1 C\H stretching Alkane compounds4. 2114.86 cm−1 C`C stretching Alkyne compounds5. 1741.64 cm−1 C_O stretching Aldehydes and saturated aliphatic6. 1653.42 cm−1 N\H stretching Amine group leading to NH2

scissoring depictingthe presence of polyamide group

7. 1574.96 cm−1 C\C stretching Aromatic ring compound8. 1544.71 cm−1 N\O asymmetric

stretchingNitro compound

9. 1461.05 cm−1 C\H bend Alkane compound10. 1340.57 cm−1 C\N stretching Aromatic amine11. 1240.93 cm−1 C\O stretching Carboxylic acid and ether12. 1202.86 cm−1

1081.06 cm−1

1033.84 cm−1

C\N stretching Aliphatic amines

13 1164.68 cm−1 O\C\C stretching Ester compound14. 1118.12 cm−1 C\H wag stretching Sulphonic acid group15. 859.58 cm−1 C\Cl stretching Alkyl halide16. 712.64 cm−1 C\H stretching Phenyl ring substitution ring17. 671.16 cm−1 Vibrations Mono-, meta- or 1,3,

5-substitution in aromatic ring

51P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

fluxdecreases. This particular phenomenon is due to the existence of con-centration polarization which has the ability to influence the membraneseparation process [63]. The effect of the concentration polarization canbe reduced with the help of feed and permeate spacers which improvesbackdiffusion [95,96]. Also by increasing the shear force at themembranesurface with high feed flow rates, the effect of concentration polarizationcan be reduced [82]. At the time of development of the concentration po-larization on the membrane surface, a specific layer is formed at themembrane–liquid interface. At this interface, the formed layer carries ahigher concentration of solute material (here p-anisic acid) than that of

Table 2FTIR analysis of NF-300 membrane.

Sr. no. Position of peakin FTIR graph

Type of vibration Presence of chemical groups

1. 3422.83 cm−1 N\H stretching Weak amides, primaryand secondary amines

2. 2923.33 cm−1 CH2 stretching Anti-symmetric type aromatics3. 2853.19 cm−1 C\H stretching Alkane compounds4. 2588.83 cm−1 COOH stretching Antisymmetric type acid group5. 2337.09 cm−1 C`N stretching Nitrile group6. 2085.45 cm−1 C`C stretching Alkyne group7. 1652.50 cm−1 N\H stretching Amine group leading to NH2

scissoring depicting thepresence of polyamide group

8. 1558.10 cm−1

1510.16 cm−1C\C stretching Aromatic ring compound

9. 1543.70 cm−1 N\O asymmetricstretching

Nitro compound

10. 1456.19 cm−1 C\H stretchingvibration of scissoringand bending type

Alkane compound

10. 1410.86 cm−1 OH bend stretching –

10. 1384.55 cm−1 C\H rock type stretching –

11. 1315.29 cm−1 C\N stretching Aromatic amine14. 1248.50 cm−1 C\O stretching Carboxylic acid and ether12. 1121.28 cm−1 C\H wag stretching Sulphonic acid group15. 1042.98 cm−1 C\N stretching Aliphatic amines16. 858.30 cm−1 C\Cl stretching Alkyl halide17. 776.25 cm−1 C\H stretching Phenyl ring substitution ring18. 673.79 cm−1 vibrations Mono-, meta- or 1,3,

5-substitution in aromatic ring19. 604.62 cm−1 C\H stretching Alkynes

the bulk of the solution [63,97]. For such type of condition, the transportof material across the membrane is mainly driven by the concentrationgradient because an increase in osmotic pressure reduces the drivingforce for mass-transfer [63,92], which results into a reduction in thepermeate flux. From Fig. 4, it has been observed that beyond the con-centration of 250 mg/L, the permeate flux is almost constant with avery little change. From the above observation, it can be concludedthat the thickness of the layer of concentration polarization is almostconstant and has moved toward the steady value, which results into astable separation [63].

Fig. 5 also shows that due to the larger pore size of the goat mem-brane, the percentage transmission of p-anisic acid for the goat mem-brane was higher than that of the NF-300 membrane. From thisobservation, an inference can be drawn that the difference in the mem-brane structure is having an impact on the transmission (or rejection)of the material, and similar findings were reported in literature [98].Here, transmission at low pressure was studied keeping into consider-ation that p-anisic acid is to be used as a dermal carrier and operate atnormal atmospheric conditions. The p-anisic acid feed solution preparedfrom 250 nm particle size for both 50 mg/L and 300 mg/L (minimumand maximum concentrations studied) was selected for further sets ofexperiments as a higher transmission was observed in Fig. 5 for thisrange and the pressure was at 4 bar. Low pressure is selected overhere in view of having compatibility with skin and from Fig. 5, it canbe said that better transmission has been derived at the said operatingconditions.

Transmission of p-anisic acid through both themembranes is linearlycorrelated with feed concentration (for the goat membrane: correlationcoefficient R2=0.998 at 4 bar; R2=0.998 at 6 bar; and for the NF-300membrane: R2=0.984 at 4 bar; R2=0.999 at 6 bar). From this data ofcorrelation coefficient (R2) it can be said that the performance of thegoat membrane in terms of transmission of p-anisic acid is almost uni-form at both the pressures and it only varies with a change in the feedconcentration and have a linear relationship. Even though in the caseof the NF-300 membrane, there is a linear relationship between thefeed concentration and transmission, the value of R2 varies with changesin operating pressure. From this it can be said that the performance ofNF-300 is affected by the pressure at specific feed concentration.

3.5. Influence of cross-flow rate

Cross-flow rate across the membrane surface is one among the im-portant factors which is having an impact on the membrane perfor-mance. To determine the effect of flow rates, experiments werecarried out at different flow rates. The effective membrane area is150 cm2, hence for a flow-rate of 15 L/min, the cross flow velocityis 0.017 m/s. The cross-flow rate across the membrane is turbulentin nature due to the mixing of streams. The findings are wellsupported with the earlier researches [82,83]. Fig. 6 shows the per-centage transmission of p-anisic acid at different feed flow rates(4–16 L/min) at 4 bar pressure. It can be seen that the transmissionis fairly constant for initial feed flow rate selected and then it startsdecreasing slightly. This is due to the reason that an increase in feedflow rate increases the turbulence over the membrane surface. This inturn reduces the boundary layer thickness which exists at the interfaceof the membrane and fluid thereby decreasing the transmission of thematerial [63,99]. The thickness of the boundary layer formation on themembrane surface is influenced by the flow pattern and viscosity ofthe material [63]. Here the experiments were conducted at 30+1 °Ctemperature, hence viscosity is almost constant and amajor influencingfactor is flow rate. By changing the flow rate, the tangential and radialvelocities of the fluid across the membrane surface were also affected,which leaves an impact on the rate of transmission and permeate fluxes[63].

At a higher feed flow rate (above 15 L/min), fouling of membranewas observed, which is visualized in Fig. 7Aa. From Fig. 6, it can be

A B

C D

Fig. 2. SEM images of NF-300membrane: (A) top surface; (B) cross-section of themembrane; (C) asymmetric view, micro-channels of cylindrical type in cross section of themembrane;and (D) micro-channels with a layer separation.

52 P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

observed that the transmission of p-anisic acid decreased with an in-crease in the cross flow rate because at a higher level of flow rate,membrane fouling was observed [100]. These results suggest thatthe present flow channel geometry is having a complex hydrodynamicscondition, whichmay be one of the reasons for the formation of crystalsat themembrane surface [101]. The foulingwasmainly observed due tothe precipitation of crystals at its surface. Here the increment in crossflow-rate has induced the formation of crystals due to a change inheat and mass balances under the conditions of turbulence, and similarfindings were reported elsewhere [100]. In this case, deliberately wehave avoided higher values of fluxes with an aim to maintain theconstant bulk conditions in the upstream of themembrane. This con-stant bulk conditions has allowed the manifestation of nucleation

A

C

Fig. 3. SEM images of a goat membrane: (A) top surface; (B) fibrous structure of membranesfibrous micro-channels; and (D) inner layer of the membrane indicates a fibrous structure

phenomena at the membrane surface. Due to the constant bulk con-ditions, incipient nucleation took place [102].

Due to the changes in the heat andmass balances in the near vicinityof themembrane, the feed solution acquires a condition of supersatura-tion. Under the supersaturation condition, the concentration at themembrane surface (i.e. concentration polarization) increases, which re-sults into the permeation of clean water and rejection of the species,leading to the crystal formation/deposition on membrane surface, andsimilar findings were reported by Kostoglou and Karabelas [103].Here, the permeate flux is a driving force for the crystal formationwithinthe range of 8 to 15 L/m2h, and it is in line with findings reported byKarabelas et al. [102]. Under the supersaturation condition, the concen-tration of p-anisic acid exceeds its solubility limit; due to which

B

D

and no pores; (C) asymmetric view, cross-section of the membrane shows zig–zag typein the membrane.

10

20

30

40

50

60

70

50 100 150 200 250 300

Concentration (mg/L)

Per

mea

te f

lux

(L/m

2 h) 6 bar, GM

4 bar, GM

6 bar, NF

4 bar, NF

Fig. 4. Variation of permeate flux as a function of concentration for different experimentalconditions (GM= goat membrane; NF = NF-300 membrane).

40

50

60

70

80

4 6 8 10 12 14 16

Cross flow rate (L/min)

% T

ran

smis

sio

n

50 mg/L, GM

300 mg/L, GM

50 mg/L, NF

300 mg/L, NF

Fig. 6. Influence of cross-flow rate on %T at a constant pressure of 4 bar (GM = goatmembrane; NF = NF-300 membrane).

53P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

crystallization may occur either directly on the membrane surface orin the bulk and subsequently deposited on the membrane surface[104,105]. The classical nucleation theory has accepted that the nu-cleation induction time varies with degree of supersaturation. Thenucleation rate of surface crystals depends on the available scale-free membrane surface area.

Karabelas et al. [102] have reported that no reliable criteria havebeen ascertained yet for the process of incipient crystallization inmembrane science which is mainly due to the complexity associatedwith the membrane. The crystal formation process on the membranesurface is a complex process like a black box and it comprises severalintermingled sub-processes which are difficult to identify [103].Kostoglou and Karabelas [103] have stated that apart from fouling/scaling, the process of desalination is also to be evaluated on thebasis of membrane crystallization. The dissolved organic materials inliquid undergo instantaneous reactions and develop concentrationfield, resulting into the nucleation and formation of crystals. This partic-ular process is governed by electro-neutrality and zero-electric currentand is supported by the well known equations such as Stefan–Maxwelland Nernst–Planck [103]. Rejection of dissolved organic materials andpermeation of water flux increases the concentration of the material

40

45

50

55

60

50 100 150 200 250 300

Concentration (mg/L)

% T

ran

smis

sio

n

4 bar

6 bar

60

65

70

75

80

50 100 150 200 250 300

Concentration (mg/L)

% T

ran

smis

sio

n

4 bar

6 bar

B

A

Fig. 5. Effect of feed concentration on p-anisic acid %T with NF-300 membrane (A) andwith goat membrane (B).

at the surface, resulting into the development of supersaturation stagewhich is sufficient enough for the precipitation of materials through anucleation stage. Here both bulk and surface precipitations may occuraccording to the prevalence of the conditions at the membrane. Duringthe process of surface precipitation, the surface particles are immobilizedand grow to larger sizes, resulting into the development of concentrationfields around them.When the level of supersaturation is higher than thecritical value, it provides a driving force for the random development ofnuclei at themembrane surface. Here the flow of the solution has its im-pact on the growth of the crystals. In such type of situations, as per theprinciple of electro-neutrality and condition of zero-current, rejectioncoefficient will equal everywhere. Another reason for the formation ofnuclei on the membrane surface is the collision of ions and their adsorp-tion at the membrane surfaces. The growth of nuclei at the membranesurface is due to the combination of diffusion in the bulk and surface re-action of the solute. The diffusion of organic material from its bulk stageto the membrane surface takes place due to the surface integration. Theparticles in the bulk phase of the liquid are under the influence ofBrownian motion and develop coagulation [103]. So under the effect ofthe Brownianmotion the nucleation, coagulation and adsorption of par-ticles take place due to the convection and diffusion of ionic species[103]. After the deposition of bulk particles at the membrane surface,they behave as surface particles; details of thismechanism, itsmodelingand pictorial description are given by Kostoglou and Karabelas [103].Here in this case, first the active compound is accrued at the membranesurface due to the rejection, but later on due to the supersaturation, theprecipitation starts, and results into the reduction of the solution con-centration [103]. As per the theory of mass and heat transfers, an incre-ment in the supersaturation level increases the formation of smallnuclei, however, this weird process is not observable [103]. The flowof feed, when it comes in contact with the membrane, behaves like aplug flow, resulting into an increment in particle size and a reductionof the diffusion coefficient [103]. Over a period of time, the surface par-ticles are stabilized due to the reduction of concentration and disap-pearance of bulk and surface nucleations. Generally, the particles aredeveloped in a bulk phase of the solution and then travel to the mem-brane surface, until the steady state condition reached at the mem-brane, and this transfer of particles continued. Under the presence ofcross-flow conditions, shear stress exists on the membrane surface[103]. Under the shear stress, the behavior of bulk particles is differentthan that of particles created on the surface [106]; here the shear forcesfavor the incipient crystal formation [103]. Chen et al. [107] have shownthat rejection/retention of material at the membrane surface is depen-dent on operational flux. The particles developed on the surface remainconnected there, but the bulk particles have a tendency to remainsuspended in the cross-flow field and thus reduce the extent of mem-brane scaling [103]. As the permeate flux increases, p-anisic acid in afeed solution acquires a saturation limit, resulting into nuclei formationand promotes growth on the membrane, typically known as scaling[99], which reduces the permeation flux [108]. Karabelas et al. [102]have pointed out that formation of crystals/scaling of membrane is

54 P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

very critical in desalination and can be studied with the help ofmodeling of the basic data of thermodynamics and kinetics. Tzotziet al. [109] have found that permeate flux is not highly influencedby the membrane scaling. More work in the direction of the studyof crystallization on reverse osmosis membrane is reported elsewhere[110].

After comparing the SEM images of Fig. 7 and Fig. 6, it can be said thatthe rate of fouling is higher in the case of theNF-300membrane,whereasit is on a lower side in the goatmembrane. The size of re-crystallized par-ticles of p-anisic acid formed and adsorbed on the NF-300 membrane ison a higher side than that on the goat membrane. From this results itcan be said that flow rate across themembrane surface is one of the im-portant factors affecting the membrane flux. The % transmission ofp-anisic acid decreases for the cross flow rate higher than 8 L/min,hence in view of the objective of maximum transmission of p-anisicacid, for further experimental study 8 L/min was considered as anoptimum value of the cross flow rate.

3.6. Influence of pH on the transmission of p-anisic acid

The pH value of the feed solution has an impact on the p-anisicacid itself andmembrane materials as well as the interaction betweenthem in the water; in view of the same it is essential to determine theeffect of pH on the membrane performance. The effect of pH on thetransmission of p-anisic acid was studied by the addition of NaOH(0.1 N) andHCl (0.1 N) to a feed solution and varying its pHs accordinglyat 4 bar and 8 L/min crossflow rates. Generally, solute rejection or trans-mission by NF membranes is expected to be dependent on the electricalinteraction between solute and membrane surfaces and it also dependson the pH of the solution. The change in the pH of the feed solution in-duces changes in the level of supersaturation [102], which results intoprecipitation of crystals at the membrane surface.

As pH increases the transmission increases to themaximum(Fig. 8A)and then starts decreasing. This is mainly due to the higher diffusivity ofH+ ions than the OH− ions at a higher pH. As we increase the pH of thefeed solution, the transmission (or rejection) of p-anisic acid reduces (or

a

a

A

B

Fig. 7. Adsorption of p-anisic acid on: (A) NF-300membrane surface: (a) crystal formation: croformation: cross flow effect; (b) crystal formation: pH effect.

increases), and similar findings of increment in pH of the feed solutionand increment in the rejection of organic material in aqueous solutionwere reported by Ahmad et al. [98]. The p-anisic acid has an aromaticring structure which induces higher hydrophobicity for the incrementof pH [98]. It can be observed from Fig. 8A that for the goat membranethe maximum transmission was observed at pH 5 and that for theNF-300 membrane at pH 4. Hence, it can be said that for the goatmembrane at pH 5 and for the NF-300 at pH 4 the membrane isoelec-tric point was approached [98].

The electric potential at the membrane surface cannot be directlymeasured, but the electric potential at the hydrodynamic plane ofshear can be determined from streaming potential measurements,known as zeta potential (ξ) measurement. Streaming potential gener-ates due to the relativemotion between fluid containing charged speciesand a charged surface caused by the hydrostatic pressure gradient.Mem-brane acquires a surface charge when it comes into contact with anaqueous solution. When under a pressure, an aqueous solution movesthrough a membrane slit, then a streaming potential is generated. Theflow of liquid gives rise to a streaming current, thereby generating a po-tential difference. The ξ is an important and reliable indicator of themembrane surface charge which interacts with its surroundings.

The calculated apparent ξ of both the membranes is shown in Fig. 9.The isoelectric point of the NF 300 membrane is near to 4 and the goatmembrane is near to 5. The goat membrane has much more surfacecharges than the NF-300 membrane at neutral conditions. As shownin Tables 1 and 2, the NF-300 membrane and goat membrane havecarboxylic acid and amine groups and therefore exhibit negative orpositive surface charges depending on the pH. Above pH 4 (for theNF 300 membrane) and pH 5 (for the goat membrane), the carboxylfunctional groups are dissociated resulting in a negatively chargedmembrane surface. Below pH 4 (for the NF-300 membrane) and pH 5(for the goat membrane), the carboxyl groups are fully undissociated,but the amine groups are protonated so that the membrane surface ispositively charged. A comparison of Fig. 9a and b shows that there isan effect of feed concentration on the surface charge of the membrane.From the comparison, an inference can be drawn that with the increase

b

b

ss flow effect; (b) crystal formation: pH effect; and (B) goatmembrane surface: (a) crystal

40

50

60

70

80

90A

B

3 4 5 6 7

pH

% T

ran

smis

sio

n

50 mg/L, GM

300 mg/L, GM

50 mg/L, NF

300 mg/L, NF

10

20

30

40

50

2 3 4 5 6 7 8

pH

Per

mea

te F

lux

(L/m

2 h) 50 mg/L, GM

300 mg/L, GM

50 mg/L, NF

300 mg/L, NF

Fig. 8. (A) Influence of pH on p-anisic acid %T (4 bar, 8 L/min); (B) variation of permeateflux as a function of pH (4 bar, 8 L/min) (GM = goat membrane; NF = NF-300membrane).

55P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

of the bulk concentration of the feed solution from 50 mg/L to300 mg/L, the charge of membrane surface also increases due to thehigher adsorption of material, and there is a shifting of the curve of ξ,and similar findings were also reported by others [111–113].

-40

-30

-20

-10

0

10

20

30A

B

1 2 3 4 5 6 7 8 9 10

pH

Zet

a P

ote

nti

al, m

V

NF

GM

-50

-40

-30

-20

-10

0

10

20

30

1 2 3 4 5 6 7 8 9 10

pH

Zet

a P

ote

nti

al, m

V

NF

GM

Fig. 9. (A) Isoelectric point, zeta potential vs. pH, 50 mg/L; (B) isoelectric point, zetapotential vs. pH, 300 mg/L.

The isoelectric point is one where minimum rejection (or maximumtransmission) occurs and is mainly due to the existence of electrostaticrepulsion forces between the charged membrane surface and solute. Ata lower pH, themembrane exhibits a positive charge and shows a higherrejection and vice-versa [98] due to the presence of the amide group inthe membrane (details of the same are as mentioned in Tables 1 and2). Fig. 8 shows that the permeate flux is highest while transmission ishighest (or rejection is lowest) [114]. It can be predicted that as thesolution pH decreases below the pKa value of 4.5 for p-anisic acid,electrostatic repulsion between p-anisic acid and themembrane surfaceis eliminated, allowing adsorption of the uncharged p-anisic acid to themembrane and the same can be visualized in Fig. 7Ab and Bb. At pHvalues above the isoelectric point, the surface of themembrane acquiresa negative charge, which increases the rejection of material. Fig. 8Ashows that at pH of 7, lower transmission (or maximum rejection) ofmaterial is mainly due to the negative charge acquired by the mem-brane pores. At this condition, p-anisic acid experiences an electrostaticrepulsion from the membrane pore, which causes its rejection by themembrane. Here the important scientific principle is electro-neutralityof the permeate solution. At a lower pH, the electrostatic repulsiveforces and rejection of the material decreases. At pH 4.0 (NF) and 5(GM), the transmission attains global maximum (or rejection attainslocal minimum), since the deficient in charge leads not only to no elec-trostatic repulsion but also to increased pore sizes and allow the passageof p-anisic acid. Both these membranes behave as both positively andnegatively charged surfaces under different pH conditions.

While elimination of charge repulsion reduces the removal rate, ad-sorption can contribute to the short-term removal of p-anisic acid. Bothprocesses occur simultaneously, and their relative contributions cannotbe separated. Thus, not significant but to some extent quitemarginal in-crease in transmission for p-anisic acid is observed at their isoelectricpoint [115]. The permeate flux was observed to be quite constant forthe entire pH range selected with higher values (Fig. 8B). Comparedto the NF-300 membrane, a sharp fall in transmission was observedwith the goat membrane on increasing the pH. With the increase inthe pH value, a degree of ionization will increase, which leads to an in-crease of adsorption capacity of the membrane and results into the re-tention of material at the surfaces, and the same can be visualized inFig. 7Ab and Bb. The crystals obtained are flat and lump type in nature,and similar findings were reported by Lee et al. [116]. As explained inSection 2.2, for maintaining the pH of the feed solution, certainchemicals were used. Some of the ions from these chemicals may ad-sorb onto the active sites of the membrane and hinder the process ofcrystal formation. As we increase the pH, the nucleation and growthof the crystals are hindered by the movement of ions across the activesites of the membrane, the evidence of the same is morphologicalchanges and alteration in the shape of the crystals [116]. The increaseof pH does not promote bulk nucleation, which means that membranesurface crystallization phenomenon is having its existence. The smallchanges in the pH resulted into the precipitation of crystals at the surfaceof themembrane [117]. As seen in Fig. 8B, the permeateflux is not havinga difference with pHs from 5 to 7, meaning the concentration polariza-tion increaseswith pH. This negative effect on the permeate flux nullifiesthe positive effect of the membrane permeability rise.

Here in this work, we have ignored the possibility of formation ofhigher molar masses at high pH in view of the reduction of transmis-sion (or increment in rejection) at a higher pH [98]. Hence it can beconcluded that the rejection (or transmission) of p-anisic acid isdue to the changes in the membrane structure caused by the solutionpH, and similar findings were reported elsewhere [98,114]. Freger etal. [118] have found that at low (acidic) pH, chemical bonds of mem-brane polymer matrix dislocate due to the hydrolysis. The hydrolysisof the membrane reduces the degree of crosslinking (i.e. rigidity) ofthe matrix. Also the hydrolysis under lower pH increases the hydrophilicsites at the membrane, which ultimately increases the permeate flux.The reduction of transmission (or increment in rejection) of p-anisic

20

30

40

50

60

70

80

90A

Per

mea

te f

lux

(L/m

2 h)

50 mg/L, GM

300 mg/L, GM

50 mg/L, NF

300 mg/L, NF

56 P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

acid at a higher pH is mainly due to the hydration swelling of the mem-brane skin layer [114]. The hydration of the membrane reduces the poresize of membrane which in turn reduces the permeation of solute.

The above findings provide valuable information for the develop-ment of a marketable product of p-anisic acid in the form of dermalointment, dermal patches,medicine and syrup. The said product of oint-ment and dermal patches for meeting the post radiation treatment incase of skin cancer and for skin desquamation should have a pH valueof above 4.5 (pKa value) and not more than 5.0 for effective diffusionof p-anisic acid through the skin membrane of patients. In the sameway for deriving better in-tissue diffusion of p-anisic acid for hepatitisB and C viruses and for HIV patients, the medicine must be in therange of 4.5–5.0 pH.

3.7. Influence of time and temperature on p-anisic acid transmission

Usually for the NF membranes, flux decreases with time due to theincrease in osmotic pressure thereby increasing concentration at themembrane surface but the permeate quality remains the same [119],which results into the retention of needle and cylindrical type crystalsat the surface of the membrane. Similar findings of retention of needle-type crystals at the membrane were observed by Lee et al. [116] fordissolved organic matter. Lee et al. [116] have also stated that the pHof a feed solution has an impact on the size and shape of the crystalformation at the membrane surface. The density (number of crystalsper mm2) of crystals on the membrane surface increases with respectto time [102].

Fig. 10 shows the transmission p-anisic acid as a function of time at aconstant pressure (4 bar) and a cross flow rate (8 L/min) for p-anisicacid feed solution. It can be seen that the percentage transmission in-creases very minutely with time. This minor increase in the transmis-sion is due to the minor decrease in the solvent permeability. Initially,a slight decrease in the transmission was observed so as to reach asteady state. The transmission effects observed were greater for thegoat membrane owing to its larger pore size and hence, allowingmore permeation of p-anisic acid through it as compared to theNF-300 membrane. In view of the changes in the body temperaturefrom person to person, a range varying from 36 to 40 °C was selectedfor better understanding of p-anisic acid transmission process throughboth the membranes (acting as a model human skin). It was also seenthat as pressure increases the percentage transmission decreases. Thiswas mainly due to the fact that when pressure increases, water fluxthrough themembrane increases andwhile solute fluxes essentially re-main unchanged as they depend on the concentration difference acrossthemembrane.When pressure across themembrane surface increased,macroscopic driving force of the permeation also increases, which re-sults into the pressing of micro-structure of the membrane and causesdistortion of transport channels, which might have closed or reducedthe area of channel or pathway to block the molecules to pass [92,93].

40

50

60

70

80

90

0.25 0.5 1 1.5 2 2.5 3

Time (h)

% T

ran

smis

sio

n

50 mg/L, GM

300 mg/L, GM

50 mg/L, NF

300 mg/L, NF

Fig. 10. Influence of time on p-anisic acid %T (GM = goat membrane; NF = NF-300membrane).

During this time, the working ability of recognized sites and cavitieswere negatively affected at a higher pressure, which results into areduction of transferring rate of p-anisic acid [94]. Thus, p-anisic acidtransport due to convection becomes more significant as compared todiffusion [97].

Fig. 11A shows that theflux increaseswith an increasing temperatureas expected [120], but in both the membranes the permeate flux almostdoubles from 30 to 40 °C with a larger increase in case of the goat mem-brane. This may be either due to reduced viscosity at a higher tempera-ture [121] or an increase of average pore radius [120] or the combinedrole of both for the establishment of flow channels through the mem-brane [122]. There is no literature available on goat membrane forcomparison, hence it can be concluded that the situation needs specificstudy. It can be seen from Fig. 11B that as temperature is increased thep-anisic acid transmission also increases. These results are in agreementwith the results already reported elsewhere [120]with a larger increasein the case of the goat skin membrane from 78.1 to 85.3% as comparedto 56.5 to 61.1% for the NF-300 membrane at 300 mg/L feed solutionconcentration. Here the significant difference observed is that the goatmembrane exhibits a higher mass transfer performance [90,97]. Astemperature increases, thermal energy gets increased, thus increasingthe diffusivity of the solute. Since transport of the solute throughpores is mainly diffusive, an increase in diffusivity of the solute resultsin an increase in solute transmission. The transmission of p-anisic acidthrough both the membranes is linearly correlated with temperature,viz., for the goat membrane: R2=0.976 at 300 mg/L and R2=0.974 at50 mg/L and for the NF-300 membrane: R2=0.939 at 300 mg/L andR2=0.962 at 50 mg/L. At both the feed concentrations the R2 valuesare on a higher side for the goat membrane.

Above information derived here from the experimental data oftemperature range is having a vital importance for the drug deliverythrough human skin. It can be said that for meeting the requirementsof local drug delivery of p-anisic acid through ointment or dermalpatch, an external aid of hot air circulation (for limited time interval)near the affected body area will deliver the expected results of betterdrug efficacy and early recovery through healing.

B

25 30 35 40 45

Temperature (oC)

40

50

60

70

80

90

25 30 35 40 45

Temperature (oC)

% T

ran

smis

sio

n

50 mg/L, GM

300 mg/L, GM

50 mg/L, NF

300 mg/L, NF

Fig. 11. (A) Variation of permeate flux as a function of temperature; (B) influence oftemperature on p-anisic acid %T (GM = goat membrane; NF = NF-300 membrane).

Table 3Comparison of true and observed transmission for NF-300 and goat membranes in thePerma®-filtration setup.

Conditions Tobs (max) % Treal (%) ΔT (%)

57P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

These particular experimentswith both themembraneswith differentoperating conditions are a kind of in-vitro experiments for simulating thereal world problems of product development in the area of local drugdelivery systems.

50 mg/L, GM 69.5 74.2 4.7050 mg/L, NF 47.3 49.5 2.20300 mg/L, GM 78.1 80.7 2.60300 mg/L, NF 56.4 60.3 3.90

Table 4Comparison of true and observed rejection for NF-300 and goat membranes in thePerma®-filtration setup.

Conditions Robs (max) % Rtrue (%) Difference (%)

50 mg/L, GM 33.8 26.1 −7.750 mg/L, NF 56.8 53.4 −3.4300 mg/L, GM 26.1 21.5 −4.6300 mg/L, NF 45.9 41.7 −4.2

3.8. Concentration polarization and mass transfer coefficient

Fig. 12A indicates that a little rise in rejectionwas observed with re-spect to an increment in the cross flow velocity. For a concentration of50 mg/L, rejection increases from 30.8% to 33.8% and 53.1% to 56.1%for the NF-300 membrane and goat membrane for an increase incross-flow velocity from 4.44×10−6 m/s to 1.78×10−6 m/s, respec-tively. In the same way, for a concentration of 300 mg/L, rejection in-creases from 22.5% to 26.1% and 44.21% to 45.9% for the NF-300membrane and goat membrane for an increase in the cross-flow veloc-ity from 4.44×10−6 m/s to 1.78×10−6 m/s, respectively. From thesedata of rejection, inference can be made that occurrence of mass trans-fer is small. The data sets of both the concentrationswere converted andplotted (Fig. 12B) in the form of ln[(1−Robs)/Robs] against Jv/un. Thevalue of n=0.67 was considered here for deriving the mass transfercoefficient, details of the same was explained elsewhere [85]. Theresulting gradients were calculated with the help of MS EXCEL spread-sheet software and constant a was determined as 1.21×10−4 m/s0.33,0.82×10−4 m/s0.33 for 50 mg/L and 300 mg/L for the goat membrane,whereas 0.44×10−4 m/s0.33, 0.83×10−4 m/s0.33 for 50 mg/L and300 mg/L for the NF-300 membrane. The difference in true to observedtransmission and rejection is reported in Tables 3 and 4. Here the effectofmass transfer (Fig. 13) isminimum for all four situations and is belowunity. The term Jv/k is a kind of dimensionless numberwhich representsthe relationship between the convective transport (Jv) and diffusivetransport (k) and is generally known as Peclet number [82]. Fig. 13shows that the value of Jv is higher than k, means convective flux of

0.2

0.25

0.3

0.35

0.4

0.45

0.5

0.55

0.6

0 0.000005 0.00001 0.000015 0.00002

Cross Flow Velocity (m/s)

% R

ejec

tio

n

50 mg/L, GM 300 mg/L, GM50 mg/L, NF 300 mg/L, NF

y = -387.2x + 0.9429

R2 = 0.8443

y = -569.6x + 1.4356

R2 = 0.8259

y = -392.89x + 0.0167

R2 = 0.788

y = -211.06x + 0.3127

R2 = 0.7405

-0.400

0.000

0.400

0.800

1.200

1.600

B

A

0.00010 0.00020 0.00030 0.00040 0.00050 0.00060 0.00070

Cross-flow Velocity (m/s)

ln[(

1-R

ob

s)/R

ob

s]

50 mg/L, GM 300 mg/L, GM

50 mg/L, NF 300 mg/L, NF

Fig. 12. Mass transfer characterization for NF-300 and goat membranes: (A) variationin observed rejection vs. cross flow velocity; (B) linear analysis for determination ofmass transfer coefficient (GM = goat membrane; NF = NF-300 membrane).

thematerial is not balanced due to the presence of higher concentrationpolarization modulus. The highest rejection found was around 7.7% forthe NF-300 membrane. The standard deviation of 8.20% was found forboth the membranes. The data indicate the existence of mass transfercorrelation and the effect of concentration polarization is visible. Thedifference of rejection data indicates that there is a moderate (3.4–7.7%)level of difference between the observed data and real data, which con-tradicts the findings of Oatley et al. [85].

Murthy and Gupta [123] have suggested that for determining themass transfer coefficient, graphical method is more suitable than filmtheory (Eq. (4)). Hence, we have plotted the data as per the equationsuggested [123]:

ln 1−Robsð Þ � JvRo

� �¼ ln

DAM

Kδ

� �þ Jv

k: ð7Þ

By using the Eq. (7), a graph was plotted between ln[(1−Robs)×Jv/Robs)] vs. Jv. The slope of the straight line will provide a value of1/k and intercept will provide a value of DAM/Kδ (solute transportparameter). The data plotted as per Eq. (7) are shown in Fig. 14,which indicates that compared to film theory (Fig. 12B) results ofmass transfer coefficient derived through the graphical method [123]are having better fittings (for linearity, higher r2 values>0.91) andmore accurate values for mass transfer coefficient. The good fitting ofstraight line (r2>0.91) for the experimental data shows thatmembraneparameters and mass transfer coefficient are independent of appliedpressure [123]. Dydo et al. [124] have used an equation similar to theequation proposed by Murthy and Gupta [97] in their study of nucle-ation kinetics in the membrane and found that the data are havinggood linearity (r2 value>0.972).

y = 0.121e0.67x

y = 0.082e0.67x

y = 0.044e0.67x

y = 0.083e0.67x

0.000

0.100

0.200

0.300

0.400

0.10 1.00 10.00

Jv [x 105 m/s)

Exp

(Jv

/k)

50 mg/L, GM

300 mg/L, GM

50 mg/L, NF

300 mg/L, NF

Fig. 13. Comparison of calculated mass transfer effect to that obtained from acorrelation.

y = 88589x - 12.654

R2 = 0.9243

y = 94156x - 12.335

R2 = 0.944

y = 88858x - 11.728

R2 = 0.9322

y = 83369x - 11.261

R2 = 0.9138

-13.0

-12.0

-11.0

-10.0

-9.00 0.000005 0.00001 0.000015 0.00002

Jv, m/s

ln[(

1-R

ob

s) x

Jv/

Ro

bs]

50 mg/L, GM

300 mg/L, GM

50 mg/L, NF

300 mg/L, NF

Fig. 14. Plot of simple graphical method for mass transfer characterization for NF-300and goat membranes (GM = goat membrane; NF = NF-300 membrane).

58 P.J. Gandhi, Z.V.P. Murthy / Desalination 315 (2013) 46–60

For both the conditions of different concentrations, the variationin the values of DAM/Kδ and k which is very less (Table 5) indicatesthe robustness of the graphical method for determining the masstransfer coefficient [123]. It is expected that the value of k varieswith the change in the feed concentration [123] and results of this re-search study confirms the same. The results show that as we increasethe cross flow velocity, mass transfer coefficient increases (Fig. 13)which in turn increases the solute rejection (Fig. 11A) [82]. AlsoFig. 13 shows that upon increasing the cross flow velocity, value ofDAM/Kδ is increasing for the same feed concentration, which indicatesthat the boundary-layer thickness of concentration polarization isaffected by the cross flow operation [82]. The rejection of p-anisicacid at the membrane surface results into the formation of concentra-tion polarization. This leads to the higher concentration of species atthe membrane surface than the bulk of the solution [102].

Both themembranes tested here have exhibited significant permeateflux and rejection (or transmission) variation under standard experi-mental conditions. The difference in the performance is mainly due totheir active layer structural non-uniformity and/or localized flaws,further details onmembrane non-uniformity are documented elsewhere[125].

4. Conclusions

The transmission study of p-anisic acid, through a nanofiltrationmembrane (NF-300) and a goat membrane, is reported in the presentwork. The performance of the membrane is affected by the processparameters. Goat membrane is having a higher transmission thanNF-300 membrane. As we increase the feed concentration, the perme-ate flux decreases and percentage transmission of p-anisic acid in-creases and eventually, shorter membrane life. Here the key role isplayed by the concentration polarization at the membrane surface. Ata higher pressure, development of macroscopic driving force disturbsthe transportation channels of the membrane, which results into a re-duction in transmission rate. Increment in feed flow rate increases theturbulence and that results into a reduction of boundary layer thicknessat themembrane surface and lower transmission of p-anisic acid. Betterdiffusivity ofmaterial can be derived in the range of 4.5–5.0 pH. Data in-dicate that the transmission rate of p-anisic acid is linearly related withfeed concentration and temperature. The present experiments at labo-ratory scale provide valuable information for the development of

Table 5Parameters estimated using graphical method Eq. (7).

Type of membrane Concentration k×105 (m/s) DAM/Kδ (m/s)

Goat membrane (GM) 50 mg/L 1.129 −12.65300 mg/L 1.062 −12.33

Nanofiltration membrane (NF) 50 mg/L 1.125 −11.72300 mg/L 1.199 −11.26

products to meet local drug delivery in dermal application and inpost-radiation treatment of breast cancer, and through in-tissue diffu-sion for treating hepatitis B and C viruses and in HIV patients.

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