polysulfone and polyvinyl pyrrolidone blend membranes with reverse phase morphology as controlled...

Journal of Membrane Science 227 (2003) 23–37

Polysulfone and polyvinyl pyrrolidone blend membranes withreverse phase morphology as controlled release systems:

experimental and theoretical studies�

Rajarshi Bhattacharya, T.N. Phaniraj, D. Shailaja∗Organic Coatings and Polymers Division, Indian Institute of Chemical Technology, Hyderabad 500007, India

Received 20 December 2002; received in revised form 2 July 2003; accepted 25 July 2003

Abstract

Blend membranes of poly(bis phenol–A-ether sulfone) (PSF) and poly(n-vinyl pyrrolidone) (PVP) in ratios (90:10 to 10:90;with increments of 10) were prepared via solution casting technique. The membranes were characterized using X-ray diffraction(XRD) and scanning electron microscopy (SEM). It was found that the blend is immiscible having the major phase of the blendhomogeneously dispersed in the continuum of the minor phase indicating the presence of “reverse phase morphology” (RPM)by SEM analysis of the dissolution treated membranes. The interaction parameterχPVP/PSF was calculated and the ternaryphase diagram with tentative spinodal along with the super-imposed experimental cloud points has been illustrated. Thesymmetric spherical geometry of the dispersed phase was explained theoretically with the help of the Flory Huggins Theory.The performance of these membranes as rate controlling membranes in controlled release applications was studied by coatingthem on paracetamol tablets and the effect of the ratio of PVP in the blend membrane on the rate of drug release was monitored.Models of mass transfer employing Fickian principles at constant temperature and pressure were elucidated to support theexperimental findings. The predicted models were found to be in excellent agreement with the experimental release profiles.© 2003 Elsevier B.V. All rights reserved.

Keywords: Barrier membranes; Controlled release; Drug permeability; Water sorption and diffusion; Reverse phase morphology

1. Introduction

The process of blending has wide applications, asit is a versatile method to tailor materials for specificend uses[1,2]. Blending techniques of immisciblepolymers in this regard has received erstwhile em-phasis; especially the membranes consisting of highmolecular weight polymers. Blends comprising ofwater soluble and water insoluble polymers are known

� IICT Communication No. 021105.∗ Corresponding author. Tel.:+91-40-719-3991;

fax: +91-40-716-0387.E-mail address: [email protected] (D. Shailaja).

to give unique swelling properties to the membranesprepared, by solution casting technique or thermalgelation [3–5]. Polymer blends having ternary sys-tems comprising of the two polymers and the solventsare explored extensively to study the influence of theirphase behavior on the properties of the blend[6–8].

Research work carried out so far throws some lighton the distinct morphologies observed in a persistentthree-phase system[9]. Hobbs et al. observed the en-capsulations among the minor components in the sys-tem, resulting in features resembling core shells. Kimet al. [10] studied the in situ kinetic behavior duringasymmetric membrane formation via phase inversiontechnique using Raman spectroscopy. The effect of

0376-7388/$ – see front matter © 2003 Elsevier B.V. All rights reserved.doi:10.1016/j.memsci.2003.07.014

24 R. Bhattacharya et al. / Journal of Membrane Science 227 (2003) 23–37

viscosity and interfacial interaction parameterχ ispronounced in the process of compatibilization. Hem-mati et al. [6,7] probed ternary phase systems anddemonstrated the role of interfacial tension and meltviscosity on the appearance of core shell encapsu-lations in PP/PS/rubber system. Another concurrentinvestigation by the same authors demonstrated theinfluence of composition of the different componentson the size of the dispersed phase.

Polymeric membranes with symmetric geometryfind avid use in the field of controlled release technol-ogy and are used with consequent success. Congruentgeometry of the membranes can result in controlledrelease close to zero order. Polymeric drug reservoirsscore over conventional drug delivery systems dueto the localization of drug action to those tissuesrequiring treatment leading to maximum therapeuticresponse. Zero order release is an excellent way ofenhancing the patient compliance to a particular drugand helps eliminating the problem of multiple dosageand side effects[11]. This can be attained more effec-tively using blend membranes having “reverse phasemorphology” (RPM) especially in reservoir type con-trolled release systems. The drug diffusion processobeys fundamental laws of “mass transfer”.

Although several researchers are working towardsachieving drug delivery systems with zero order re-lease, the method of using reverse phase morphologyfor the same has not been extensively utilized. Thecharacterization and morphology of ternary blendedsystems, exhibiting reverse phase morphology hasso far not been meticulously probed. The presentwork therefore is aimed at the preparation of poly(bisphenol–A-ether sulfone) (PSF)/poly(n-vinyl pyrroli-done) (PVP) blend membranes and their characteristicmorphology was studied using scanning electron mi-croscopy (SEM) and X-ray diffraction (XRD). Theutility of these membranes with specific morphologyas rate controlling membranes was studied by coatingthem over paracetamol tablets to monitor their releaseprofiles in aqueous medium. The quantitative estima-tion of the drug released was done experimentallyand a plausible theoretical model complementing theexperimental observations has been presented. Thecoexistence of the two phases in the polymer blendwas theoretically explained with the aid of FloryHuggins Theory. The occurrence of the character-istic reverse phase morphology of the membranes

was explained theoretically from the point of viewof viscosity, interaction parameter and surface chargeon the polymers. The behavior of water soluble andwater insoluble polymers in solution was consideredto be analogous to that of an emulsion.

2. Materials

The materials used in the preparation of blend mem-branes are (1) polyvinyl pyrrolidone from Aldrich andits Mw is 1,60,000. Polysulfone used was Udel 1700from Amoco (2). Dichlromethane (DCM) solvent waspurchased from SD Fine Chemicals, India.

2.1. Membrane preparation

Appropriate amounts of PSF/PVP depending on theweight percent were taken and a 5% (w/v) solution ofthe blends and pure polymers were prepared dissolv-ing in dichloromethane as solvent. Sufficient time wasgiven for the polymers to dissolve (12 h) and then so-lutions were cast over mercury at room temperature.After 12 h the dry films were removed and kept in avacuum oven at 45◦C for another 6 h. The thicknessof the dry film was found to be 110± 10�m whenmeasured with a dial gauge.

2.2. Solution viscosity and cloud point measurement

The viscosity of the dilute pure polymer solutionsin DCM was measured using Ubbelhode viscometer(Schott, Gerate, Germany) at a constant temperatureof 25◦C. The viscosity of the PVP was found to be1.95 dl/g and that of PSF was 1.25 dl/g. The cloudpoints of the casting solutions were obtained by notingthe volume fraction of the solvent evaporated at thetime of turbidity appearance in the otherwise clearsolutions.

2.3. Preparation of buffer solution

The buffer was prepared by mixing appropriateamounts of sodium dihydrogen orthophosphate(0.2 mol/l) and disodium hydrogen phosphate(0.2 mol/l) which resulted in a solution of 7.4 pH(physiological pH). Solution ‘X’ was prepared by dis-solving 6.97 g of sodium dihydrogen orthophosphate

R. Bhattacharya et al. / Journal of Membrane Science 227 (2003) 23–37 25

in 250 ml of distilled water added. Taking 7.098 g ofdisodium hydrogen phosphate in 250 ml distilled wa-ter made solution ‘Y’. Nineteen milliliters of ‘X’ and81 ml of ‘Y’ were mixed and made up with 200 mlof distilled water, which resulted in a solution of pH7.4. The pH was measured using a GLOBAL DPH500 pH meter.

2.4. Dissolution treatment of the membranes

The buffer solution was taken in a beaker and keptin a USP20 dissolution rate tester. The tester is filledwith water to a prescribed height. The temperature ofthe water bath was set at 37◦C. Samples of 2 cm×2 cm were taken and immersed perpendicularly in thebeaker hooked to a copper wire. The paddle speedwas set at 13.089975 rad/s (125 rpm) to ensure propermixing. Samples were subjected to dissolution for 4 h,such that the water soluble PVP gets dissolved in themedium. After 4 h, the samples were taken out of therespective solutions and were submitted to SEM, tostudy the effect of treatment on the membrane mor-phology.

2.5. Polymer coating of the tablet

Release studies were done using paracetamol tabletscoated with polymer solution by immersion coatingmethod. In this method, 5% (w/v) solution of the poly-mer blend was taken in a porcelain crucible and eachtablet was dipped in the solution to give a coat ofthickness 150± 10�m, which was peeled and mea-

y = 0.0033x

R2 = 0.9996

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

0 100 200 300 400 500 600

conc (ppm)

abso

rban

ce

Fig. 1. Calibration plot of acetaminophen drug concentration vs. absorbance. Line of best fit:y = 0.0033x andR2 = 0.9996.

sured using a dial gauge. In order to obtain the abovethickness, several concentrations were experimented.These tablets were dried in an oven at 40◦C, and fur-ther dried under vacuum at 50◦C for 48 h to removetraces of the solvent (DCM). Weight of the polymerrequired for coating a tablet was 15± 1 mg.

2.6. Calibration plot

The stock solution was prepared by dissolving oneparacetamol tablet (500 mg) in 250 ml of acid buffer.Solutions of appropriate dilutions were prepared andthe optical densities of various concentrations weremeasured using a Hitachi U2000 spectrophotometer at296 nm which is theλmax of the drug (acetaminophen)present in the paracetamol tablet. A calibration plotis shown inFig. 1, by plotting concentration versusoptical density.

2.7. Release studies

Coated tablets were taken in beakers containing250 ml buffer and kept in a shaker water bath main-tained at 37◦C and 13.089975 rad/s (125 rpm). Therelease study for each composition was done in trip-licate. Periodic assays of samples after every half anhour were taken by pipetting out 5 ml of the bufferand quickly placing the tablet in a beaker with freshsolution of buffer. The samples were assayed by UVspectrophotometer set at 296 nm. The release charac-teristics are observed for a period of 8 h. A plot ofdc/dt versust was plotted to study the release kinetics.


2.8. Scanning electron microscopy

Samples of dimension 10 mm× 10 mm weremounted on aluminum stubs using double cellophanetape and these samples were gold coated using aHUS-GB vacuum evaporator. The coated sampleswere viewed in a Hitachi S-520 scanning electronmicroscope at an acceleration voltage of 10 kV.

2.9. X-ray diffraction

Samples of 3 cm× 2 cm were submitted for X-rayanalysis to study the miscibility of blends. A SeimensD-5000 powder X-ray diffractometer was used witha 2.2 kW sealed copper tube as source and a graphitecrystal as monochromator.

3. Results and discussions

3.1. Blend morphology

The membranes of the pure polymers appear tobe homogeneous smooth and transparent. Some ofthe blend membranes look turbid may be due to

Fig. 2. Scanning electron micrographs (magnification 5.00K) of pure and PSF/PVP blend membranes: (A) pure PSF; (B) (PSF/PVP) 90:10;(C) 70:30; (D) 60:40; (E) 50:50; (F) 30:70; (G) 10:90; (H) pure PVP polymer.

the sensitivity of PVP to moisture and also becauseof the immiscible nature of the two polymers. TheSEM pictures of the pure and blends are shown inFig. 2A–H. The SEM pictures of the blends weresmooth and up to 70:30 (PSF:PVP) blend. A phaseseparation of the PVP in the PSF matrix was visi-ble from 60:40 (PSF:PVP) blend onwards as seen inFig. 2D. The number of the spherical domains of thedispersed phase increased with increasing content ofthe PVP in the blend composition. The average sizeof the PVP domains was in the range of 3–5�m in allthe compositions. In 50:50 blend, a roughness of thecontinuous phase was found, showing the possibilityof exchange of phases of the two polymers. How-ever, an exchange of phases was not noticed since thenumber of the dispersed spherical domains increasedwith further increase in the PVP content up to 10:90(PSF:PVP). The domains of 6�m size are seen in the10:90 (Fig. 2G) blend indicating not only the increasein the number but also the size of the domains. Had aphase exchange taken place, the SEM pictures from40:60 to 10:90 would have had similar number of dis-persed spherical domains to that of the 60:40 to 90:10blends. This indicates non-occurrence of a phase ex-change even though the content of the PSF was lower


Fig. 3. Scanning electron micrographs (magnification 5.00K) of blend membranes of PSF/PVP treated in buffer medium of pH 7.4 after3 h. (A) PSF/PVP (90:10); (B) 80:20; (C) 70:30; (D) 10:90.

in the blend that still remains as a continuum of themembrane. Such a behavior is known as reverse phasemorphology, a condition of the polyblend wherein theminor component forms the continuous phase and themajor component a dispersed phase[12].

In order to confirm the RPM, the SEM of the mem-branes treated with a buffer were taken to observe themorphological changes due to dissolution of the PVPportion of the membranes. The figures of the treatedmembranes are shown inFig. 3A–D. The pores formedwere of the same size of the domains which are seenin the untreated membranes. Pores were noticed evenin the 90:10 and 80:20 blends although heterogene-ity of the phases was not seen in the correspondinguntreated membranes. This indicates that the PVP ispresent as dispersed phase coexisting with PSF in allcompositions of the blend. The number and the size ofthe pores increased with increase in the content of PVPof the blend. In case of an exchange of phases in the50:50 blend, the picture would have shown a porousbehavior of the continuum along with the pore forma-tion in the dispersed phase showing an interpenetrat-ing bicontinuous phase. The absence of this featureaccords the absence of conversion to normal phase at50:50. However, the SEM pictures of 60:40 onwardscould not be taken since the film was not intact likeothers on treatment in buffer solution. This could bemainly because of the occurrence of the PVP domainsin more than a single layer leading to non-uniformityand agglomeration of the spheres that causes the irreg-ular shaped PSF pieces of the membrane to fall apart.

The phase morphology of the PSF/PVP blend mem-branes has been investigated using XRD and SEM.The XRD patterns of the pure polymers show thatthey are of amorphous nature as shown inFig. 4A–G.

The PSF diffraction patterns do not show any partic-ular diffraction peaks with high intensity, whereas thePVP shows a weak peak between 10 and 15◦ Braggangle. All the blend compositions show a broad anddiffuse peak. This indicates that PSF/PVP blends arecoexisting over the entire range of composition hav-ing an ordered arrangement of the two phases, whichis also seen in the SEM figures where presence of auniform distribution of phases is noticed. As the PVPcontent of the blend increases it was observed thatthe area under the peak decreases and from Bragg an-gle 20◦ the peak shifts to 10◦ which is the diffrac-tion peak of pure PVP polymer. This could be due tothe agglomeration of the PVP spheres when its con-tent in the blend increases beyond 1:1. Thed spacingsare found to become larger indicating the presence ofsome phase segregation in the blend with increasingPVP content of the blend. In spite of the phase separa-tion, the broad intense peak in all the blends in com-parison to the pure polymers indicates the presence ofan ordered structure of the coexisting phases which isalso supported by the SEM pictures.

3.2. Theoretical accounting for blend morphology

3.2.1. Phase separationAn approximate calculation of the spinodal for the

ternary system comprising of two polymers and a sin-gle solvent was done following the method of Scott[13,14]. The interaction parameter between the PVPand PSF was calculated using the Scott’s equation,

χAB(cr) ≈ 16(δP1 − δP2)

2 (1)

where δP1 is the solubility parameter of polyvinylpyrrolidone (22.00 MPa),δP2 the solubility parameter


of polysulfone (20.66 MPa), andχAB(cr) was foundto be 0.29. Polymer solvent interaction parameterχpoly/sol was calculated for both PVP and PSF sepa-rately, using the relation:

χpoly/sol = (1 + x0.5)2

2x

where ‘x’ is the volume ratio of the polymer repeatunit of the respective polymer to 1 mol of the solvent,i.e. dichloromethane[14].χPVP/DCM was calculated to be 0.5155 and

χPSF/DCM was found to be 0.5244. The points ofintersection of the spinodal on the PVP/PSF axis inthe ternary phase diagram can be calculated from the

Fig. 4. X-ray diffraction of pure PVP, PSF polymers and their blends: XRD of pure polysulfone polymer; PSF/PVP (90:10) blendmembrane; PSF/PVP (70:30) blend membrane; PSF/PVP (50:50) blend membrane; PSF/PVP (30:70) blend membrane; PSF/PVP (10:90)blend membrane; pure PVP membrane.

following equation[14]:

φ0

{1

X+ (χ02 − χ01 − χ12)φ1

}

×{

1

Y+ (χ01 − χ02 − χ12)φ2

}+φ1{1 + (χ12 − χ01 − χ02)φ0}×{

1

Y+ (χ01 − χ02 − χ12)φ2

}+φ2{1 + (χ12 − χ01 − χ12)φ0}×{

1

X+ (χ02 − χ01 − χ12)φ1

}= 0 (2)

by settingφ0 = 0 and usingφ1 + φ2 = 1.


Fig. 4. (Continued ).

φ1 and φ2 represent the volume fractions of PSFand PVP, respectively.

The critical solution point is calculated from thisequation of Scott[14], i.e.

χAB(cr) = 1

2

{1

X1/2+ 1

Y1/2

}2{ 1

1 − φs

}(3)

Substituting the value ofφs obtained in the equationof the spinodal

(1

φs+ 1

φ1X−2χPSF/DCM

)(1

φs+ 1

φ2Y − 2χPVP/DCM

)

−(

1

φs+χPSF/DCM+χPVP/DCM − χPSF/PVP

)= 0


Fig. 4. (Continued ).


0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.00.0

0.2

0.4

0.6

0.8

1.0

1.00DICHLOROMETHANE

0.805

0.690

0.575

0.460

0.345

0.2300.115

phase zone critical solution point one

immiscible zone

Polysulfone Polyvinylpyrolidone

0.930

Fig. 5. Cloud point curve with approximate spinodal (→); calculated spinodal (�); cloud points (—) experimental cloud point fit withpolynomial regressiony = −0.23243+ 2.6219x− 2.50195x2. For explanation of construction seeAppendix A.

The points of intersection of the spinodal on thePVP/PSF axis were obtained as depicted inFig. 5where a tentative spinodal curve is obtained by fittingthese three points in a smooth curve. Simultaneously,an experimental spinodal is also superimposed in thesame figure, which was obtained by taking the ex-perimental cloud points of the PSF/PVP solutions inTable 1.

The spinodal behavior confirms the immiscibilityof the two phases of the blend in most of the compo-sitions. The dilute solutions are clear and as they get

Table 1Critical volume fractions of DCM corresponding to the cloudpoints

PVP (%, v/v) PSF (%, v/v) Critical volumefraction of DCM (v/v)

10 90 0.1420 80 0.230 70 0.340 60 0.3650 50 0.4360 40 0.5270 30 0.4380 20 0.4690 10 0.4

We find a close match of the theoretical curve with that of exper-imental.

concentrated while formation of films on casting turnturbid due to the immiscibility of the two polymers.The blend films are therefore opaque in comparison tothe pure ones but are smooth may be due to the uni-formly distributed phases that coexist together makingthe blend a compatible one.

The phase rule enunciates that in the emulsion thedispersed phase can be conveniently increased uptoa volume fraction of 70% without phase inversion[15]. The blend membranes have shown a reversephase morphology as seen in the SEM pictures withthe major phase dispersed in the minor phase of theblend.

3.3. Theoretical explanation for the characteristicspherical shape of the dispersed phase

The appearance of the characteristic spherical mor-phology of the PVP phase dispersed homogeneouslyin the continuum of the PSF matrix has been ex-plained by taking an analogy of the emulsion whereinPVP domains are dispersed in the PSF/DCM solution.This is by virtue of greater surface tension and higherviscosity of PVP in comparison to PSF. The PVPmolecules adhere to one another by a process compa-rable to flocculation in liquid medium. This process


can be treated as the diffusion of a spherical particleof PVP in the PSF and DCM medium that has a finiteviscosity (η).

The rate of reduction of particles due to flocculationcan be written as[16]

1

N− 1

N ′ = βrt (4)

where N′ is the number of particles initially,N thenumber of particles in the end of flocculation, andβris the rate constant of flocculation.

PVP is normally used as a colloidal stabilizer inmost of the polymer reactions, mainly due to the pres-ence of the lone pair of electrons on N and O of thePVP molecules contributes to the surface charge on themolecules. The surface charge of PVP plays an impor-tant role in rendering the stability for PVP sphericaldomains in the blend solution with significant repul-sion and therefore not allowing them to flocculate.

The repulsion energy between any two particleshaving surface charge[16] can be given as

φr =[

64NkTΥ 2

κ

]exp(−dκ) (5)

where d is the distance of separation,N the num-ber of particles in the system,κ the Debye–Huckelapproximation parameter,k the Boltzmann constant,T the absolute temperature,Υ = [exp(zeψ/2kT) −1]/[exp(zeψ/2kT)+ 1], z the valence number of PVP,e the electronic charge= 1.6× 10−19 C, andψ is thepotential at the point of closest approach of anotherglobule; the distance measured from the center of theglobule under consideration(taken to be a constant ofapproximately 25 mV).

The final expression for the potential energy of re-pulsion can be calculated by numeric integration[16].It is given by

φr =[

64ΠRNkTΥ 2

κ2

]exp(−sκ) (6)

Hence, maximum repulsion occurs atrmin = s, whenφr = φm:

The stability of emulsions is further accounted forby a term stabilization ratio which is given by

W = 2R∫ ∞

2Rexp

(φr

kT

)r−2 dr (7)

3.4. Approximate calculation of W

We generate a Taylor series expansion ofφr,

rmin = s:

φr ≈φm+(r − s)(∂φ

∂r

)m

+ (r − s)22

(∂2φ

∂r2

)m

+ · · ·

Taking these terms only and considering the fact thatat maxima∂φ/∂r = 0.

On substituting it inEq. (7), we get:

W = 2Rexp

(φm

kT

)∫ ∞

2Rexp

×({(r − s)2

2

}(∂2φ/∂r2)m

kT

)r−2 dr (8)

Now we consider the fact thatW falls off rapidly tozero on either side of the maxima, then the exponentialterm within the integral contributes most significantlyof all (as a potential weight function) to converge theintegral to zero. Hence, the termr−2 is approximatedasr−2

min.Denoting the expression{(∂2φ/∂r2)m/kT)/2} as a

and replacing the variable (r − s) by t and therebychanging the lower limit from 2R to 2R − s, we getthe final form as,

W =(

2R

r2min

)exp

(φm

kT

)∫ ∞

2R–Sexp(at2)dt

Since the dimensions of the spherical domains are inthe order of some microns, we approximate the term2R− s to be almost 0, with a little error.

The integral now becomes familiar to the knowngamma function wheren = 0:∫ ∞

0xnexp(ax2)dx = 1

2

√Π

a, whenn = 0

In Eq. (7), in order to get the area under the energycurve on both sides of the maxima we multiply with2. Eq. (8)now takes the final form as

W =(

2R

r2min

)exp

(φm

kT

)(√Π

a

)(9)

The rate constant for slower flocculationβs is hencegiven as

βs = βr

(2R/r2min)exp(φm/kT)√Π/a


It is evident from this final expression that there is aretardation in the rate of flocculation and as the num-ber of particles increase (φm) also increases andβsdecreases further. Thus, it can be theoretically inferredthat as the amount of PVP increases the number ofspherical domains also increase as observed from theSEM pictures. If other factors are assumed to remainconstant,Eq. (6) shows thatφm varies linearly withthe no. of particles in the system and becomes dou-ble as the concentration is doubled if the constants aretaken to be unity. This explains the increase in the for-mation of spherical PVP portions as the PVP contentincreases as seen in SEM pictures causing the occur-rence of RPM and also the stability of the dispersedPVP phase in the blends.

3.5. Controlled release performance

The application of the blend membranes in con-trolled drug delivery as rate controlling membraneswas studied by coating the polymer solutions on to amodel drug (paracetamol). Effect of composition vari-ation on the drug release was studied to find the op-timum performing coating composition that can giverelease close to zero order. The aim of the coating is toreduce the intake of more number of doses providingthe biologically effective concentration in therapeuticlevel. The change in concentration for a particular in-terval of time (dc/dt) versus time (h) was plotted for(PSF/PVP) 90:10, 80:20, 70:30, 60:40 and 50:50 com-positions. The release profiles are shown inFig. 6. Itcan be seen from the above figure that all composi-tions of blends show an initial burst effect, which canbe attributed to the greater concentration differentialpresent at the start of the process.

After this initial burst effect, which takes place in

Fig. 6. Effect of blend composition on the release of acetaminophenin pH 7.4 buffer at 37◦C (ratios indicate PSF/PVP).

the first half an hour the drug concentration level inthe medium drops and becomes steady for rest of theperiod. The drug releases in a controlled fashion forabout 8 h and the drug released increases with the in-crease in PVP content of the blend. Thus, the 50:50sample showed maximum release due to increasednumber and size of the pores in comparison to the90:10 sample which showed the minimum. An expo-nential decrease of the drug released is seen with in-crease in the content of the PSF of the blend.

3.6. Theoretical explanation of the drug release

The drug is presumed to dissolve slowly into thepermeating aqueous phase and to diffuse out throughswollen PVP and later through the pores formed dueto its dissolution[17].

The release of the drug in to the aqueous mediuminvolves two steps:

• Step 1: Swelling process of PVP(a) Sorption of water in to the polymer membrane

causing dissolution of the drug into the sorbedmedium.

(b) Diffusion of the drug in to the water present inthe swollen PVP portions of the blend mem-brane until equilibrium is attained.

• Step 2: Release of the drug from the tablet into themedium that comes in contact with it after poreformation in the coated membrane.

3.6.1. Step 1A schematic representation of the swelling process

is given inFig. 7. It elucidates the simultaneous pro-cesses that take place as described above.

3.6.1.1. Process 1. The release of the drug into wa-ter explicitly fits in to the Fick’s second law of diffu-sion, i.e.

∂c

∂t= ∂

∂x

(D∂c

∂x

)(10a)

whereD is the diffusion coefficient henceforth in allthe systems in our calculations is taken as constant.

Obtaining a power series solution forEq. (10a)weget:


Fig. 7. Pictorial representation of the swelling process.

C = 4C′

Π

∑ 1

(2m+ 1)sin(2m+ 1)

Πx

hexp

×[−D′(2m+ 1)2Π2t

h2

](10b)

whereC′ is the concentration of the drug in the poly-meric phase (=εC′′), C′′ the solubility of the drug inPVP, ε the porosity of the polymeric membrane,D′the diffusivity of the drug in the PVP portion of theblend membrane (=P/S), P the permeability,S is thesolubility of the drug in the PVP.

3.6.1.2. Process 2. Assume that the polymer dis-solves faster than the drug.

The flux of dissolution of polyvinyl pyrrolidone canbe taken as split in to two factors:

(a) flow of dissolved PVP into external sink ormedium;

(b) flow of solvent into the polymer membrane.

Polymer flux:

J̄p = −Dp∂C

∂x(11a)

Solvent flux:

J̄s = −Ds∂C

∂x(11b)

whereDp and Ds are the intrinsic diffusivities ofPVP and water, respectively. Total volume transfer isgiven by J × v, where v is the respective specificvolumes of the polymer and solvent.

Jvp = −vpDv(p, s)

∂C

∂x(11c)

Jvs = −vsDv(s,p)

∂C

∂x(11d)

Dvp, s: diffusivity of PVP into medium;Dvs,p: dif-fusivity of medium into PVP.

Since simple dissolution takes place with no volumechange:

Jvp = Jvsvpcp: volume fraction of the polymer;cp: concentra-tion of the polymer;vp: specific volume of the poly-mer.

Similarly, volume fraction of the solvent= vscsSince there are only two components we can say

that

vscs + vpcp = 1

Differentiating partially with respect tox we get:

vs∂cs

∂x+ vp

∂cp

∂x= 0 (12)

φp andφs are the respective volume fractions of thepolymer and water.

In the swollen state the polymer has restricted chainsegmental mobility[17] where negligible diffusion ispossible, Therefore,D ≈ 0;

Hence, we have:

D = Ds(1 − φs) (13)

During the process of dissolution of the PVP por-tion of the polymeric membrane,M is taken as the


reference or origin and movement of the solvent frontis measured from here in terms of a rate of penetrationgiven by ds/dt = ◦s

AssumingJvs ≈ ◦s it can be shown that

ds

dt= −Dvs

∂c

∂x(14)

On integration and replacing◦sl by −vsD̄'C [17],and considering that the concentration of the sol-vent at the border plane between the polymer andthe swollen layer to be negligible at the onset ofdissolution, we have

◦s = D̄

l(15)

wherel is the thickness of the swollen surface of PVPandD̄ is the mutual diffusion coefficient.

During dissolution, the aqueous solution is stirredat a constant rpm and thereforel is constant. Hence,it can be concluded that◦s is a constant, i.e.

◦s = KwhereK = D̄/ l.

On integration ofEq. (14)from 0 tot from the originwe obtain,

S = Kt

It can be seen fromFig. 8 thath = d − s.Substituting fors by Kt and insertingh in Eq. (10b)

we get

Qt

Q∞= 1 − 8

Π2

∑[1

(2m+ 1)2

]exp

×{−D(2m+ 1)2Π2t

[d − Kt]2

}(15a)

Fig. 8. Pictorial representation of drug diffusion after pore forma-tion.

[d − Kt]2 when expanded binomially can be approxi-mated asd − 2Kt with slight error.

Replacing 2K by K′, inserting it in Eq. (15) anddifferentiating we get(

1

Q∞

)dQtdt

=(

8

Π2

)∑{1

(2m+ 1)2

}exp

×{−D(2m+ 1)2Π2t

d −K′t

}

×{−D(2m+ 1)2Π2d

[d −K′t]2

}(16)

Now with increasing ‘t’ it can be clearly seen that theterm−D(2m+1)2Π2t/[d−K′t] decreases, thereforethe exponential function decreases progressively.

Utilizing this function as a weight function coupledto the polynomial−D(2m+ 1)2Π2d/[d −K′t]2.

It can be concluded that the whole expression for therate, decreases with increasing time because of the factthat exponential functions converge or diverge morerapidly than algebraic functions. Thus the rate curveexhibits a steep fall as observed in the experimentalrelease curves in the initial half an hour showing aburst of the drug with high optical density.

3.6.2. Step 2In this part, we can consider that the release mech-

anism to be analogous to the release of the drug froma slab into water, which is schematically shown inFig. 8.

The solvent in the pore creates a Nernst diffusionlayer thus giving rise to a steady concentration gra-dient. The rate of transport across a plane of unitcross-sectional area can be written as

dQ

dt=[Ds

l

](Cs− C′s) (17)

C′s: drug concentration in the matrix atx = 0; Ds:diffusivity of the drug in the tablet matrix.

Rate of transport of the drug molecules across theNernst diffusion layer can also be represented as

dQ

dt= Da

h(C′a− C∞) (18)

where C′a is the concentration of drug in the water atx = 0, C∞ the concentration of drug in the water atx = h, Da the diffusivity of the drug in water,K =


Cs/Ca, whereK is the partition coefficient of tabletmatrix and water.

EquatingEq. (17) and (18)and solving for the un-known C′s yields:

dQ

dt= Ds

l

[Cs−

(CsDsh+Da lC∞

(Dal/K)+Dsh

)](19)

Release of the drug can also be written as

dQ = C dl− 12Cs dl (20)

Average value of Cs is taken because, the concentra-tion gradient is a straight line as Fig. 9,C is the totalconcentration of the drug in the tablet matrix.

Taking the time differential and performing the re-quired integrations[17] it can be shown that,

Q =(−DshC

Da

)+[(DshKC

Da

)2

+ 2DsCsCt

]1/2

(21)

anddQ

dt= CDs Cs

[(DshCK/Da)2 + 2CDsCst]1/2(22)

Considering the fact that it takes almost an hour forthe drug to completely dissolve in the medium it canbe understood that ‘l’ is negligible initially, i.e. for thefirst 10–15 min of the release.

Considering thatl ≈ 0, which is negligible whileC is large, the term [DshCCs/DaCa] becomes greaterand the rate of release can be therefore approximatedasdQ

dt= CaDa

h(23)

Hence, it can be seen that the mechanism proposedfor the release of drug by this mathematical modelreadily accounts for a steady and constant release ofdrug through the PVP pores. This finding is in excel-lent agreement with our observed experimental resultsfor the initial burst effect immediately after the ap-pearance of the pores on the membrane.

However, we can see that with elapsing time theterm 2CDsCst becomes significant and cannot beneglected as taken earlier and after some time theconstant rate can be found to decline, varying with theinverse of

√t. This behavior of the release pattern can

also be seen from the trend in the experimental graph.

4. Conclusions

The PVP–PSF blend membranes in various ratioswere prepared to study their morphological character-istics and application as controlled release systems.The blends were found to be immiscible due to thehydrophobic and hydrophilic nature of the polymers.However, the membranes were compatible over en-tire range of compositions showing a very organizedarrangement of both the phases with PVP disperseduniformly in the continuum of the PSF even when itwas the major component. Thus showing the reversephase morphological behavior of the membranes thatwas confirmed by SEM and XRD studies on bothtreated and untreated membranes. The controlledrelease performance of these membranes as rate con-trolling membranes has proved their utility by show-ing a constant release after the initial burst effect. Adecrease in the release was found with decreasingcontent of PVP in the polyblend because of the lowernumber and size of the pores formed. The diffusionprocess was explained theoretically using Fick’s lawsand the exponential decrease in the release with timewas accounted for that was found to be in goodagreement with the experimental findings. These hy-drophobic and hydrophilic blend membranes can besafely used in controlled release applications mainlybecause of the symmetric geometry with which theyare arranged in the membrane.

Appendix A

TheY axis of the rectangular co-ordinates has beentaken as a base to construct the triangular phase dia-gram using the software ORIGIN. The side of the equi-lateral triangle has been taken as a projection of theYaxis, since in the present case,φPVP+φPSF+φDCM =1 (where theφ’s are the respective volume fractions(v/v) and therefore no units are shown.

Hence,

φPVP = 1 − (φPSF+ φDCM)

To construct the cloud point curve and spinodalonly two independent variables are needed, while thethird one gets automatically fixed. So, with appro-priate transformations, an oblique pair of coordinateswas generated.


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polysulfone and polyvinyl pyrrolidone blend membranes with reverse phase morphology as controlled...

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