European Polymer Journal 44 (2008) 3222–3230

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European Polymer Journal

journal homepage: www.elsevier .com/locate /europol j

Development of sterculia gum based wound dressingsfor use in drug delivery

Baljit Singh *, Lok PalDepartment of Chemistry, Himachal Pradesh University, Shimla-171005, India

a r t i c l e i n f o

Article history:Received 11 March 2008Received in revised form 13 June 2008Accepted 9 July 2008Available online 17 July 2008

Keywords:HydrogelsPolyvinyl alcoholSterculia gumWound dressing

0014-3057/$ - see front matter � 2008 Elsevier Ltddoi:10.1016/j.eurpolymj.2008.07.013

* Corresponding author. Tel.: +91 1772830944; faE-mail address: baljitsinghhpu@yahoo.com (B. S

a b s t r a c t

The present study deals with the modification of sterculia gum to develop the novelwounds dressing for the delivery of antimicrobial agent (tetracycline hydrochloride). Thesterculia crosslinked PVA (sterculia-cl-PVA) hydrogels were characterized by FTIR andswelling studies. For the evaluation of swelling and drug release mechanism, the swellingkinetics and in vitro release dynamics of model drug from this matrix were studied in solu-tion of different pH and simulated wounds fluid. Per gram of polymer has taken (8.3 ± 0.1)g of simulated wounds fluid and has released (0.820 ± 0.6) mg of drug in the simulatedfluid. The value of the ‘n’ (0.84) indicates the non-Fickian diffusion mechanism for therelease of drug in simulated fluids.

� 2008 Elsevier Ltd. All rights reserved.

1. Introduction

Dressings have been applied to open wounds for cen-turies. Traditionally these have been absorbent, perme-able materials, i.e. gauze, which could adhere todesiccated wound surfaces, inducing trauma on removal.However, now a days, many new dressings have beendesigned to create a moist wound healing environmentwhich allows the wound fluids and growth factors to re-main in contact with wound, thus accelerating woundhealing [1]. Equally important is their ability to lock exu-date in the dressing such that upon removal from awound surface bacterial dispersion is minimized [2].Retaining an appropriate level of moisture at the inter-face between a healing wound and an applied dressingis considered to be critical for effective wound healing.Failure to control exudate at this interface can result inmaceration or drying out of the wound surface [3]. Inmost of the cases, these new dressings are based onpolymeric hydrogels which are three-dimensional net-works those swell quickly by imbibing a large amount

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x: +91 1772633014.ingh).

of water. These closely resemble the living tissuesbecause of their high water contents, soft and rubberyconsistency and their biocompatibility to tissue andblood [4].

Hydrogels have been used for the management andcare of wounds. These have all the characteristics re-quired for ideal wound dressing [5]. Healing under thewet environment of the hydrogel dressing has someadvantages, which include faster healing rate, easier tochange the dressing, i.e. the hydrogel can be peeled offwithout any damage to the regenerated surface and nodressing material remains on the wound [6]. Hydrogelsalso help to maintain a moist wound environment recog-nized as being beneficial in wound healing by promotingnatural debridement, hydrating necrotic tissue and loos-ening and absorbing slough and exudate in a variety ofwounds [7,8]. Subcutaneous implantation studies in micehave shown that in vivo the hydrogels are biocompatiblesince the foreign body reaction seen around theimplanted hydrogel samples is moderate and becameminimal upon increasing implantation time [9]. Hydro-gels are also useful for the preparation of controlledrelease devices in the field of wound dressing [10,11].The release of minocycline hydrochloride from the

B. Singh, L. Pal / European Polymer Journal 44 (2008) 3222–3230 3223

wound dressings prepared for the treatment of severeburn wounds composed of chitosan film and minocyclinehydrochloride in commercial polyurethane film as abacking has occurred in very controlled and sustainedmanner [12].

Hydrogels are prepared from synthetic and naturalpolymers. But blends of both represent a new class ofmaterial with better mechanical properties, biocompati-bility and flexibility than those of the single components[13]. Recently blends of the synthetic polymers with nat-ural polymers such as starch [14], cellulose [15], chitin[16], chitosan [17,18], cotton [19], gelatin [20,21], algi-nate [22], dextran [23] have been reported for thedevelopment of wounds dressings. Polyvinyl alcohol(PVA)-polysaccharides hydrogels have been observed tobe suitable for producing transparent, flexible, mechani-cally strong, biocompatible, effective and economicalhydrogel dressings. Using 0.5–2% concentration of poly-saccharides resulted in increase of tensile strength from45 g/cm2 to 411 g/cm2, elongation from 30% to 410%and water uptake from 25% to 157% with respect toPVA gel without polysaccharides [17]. In another study,gelatin has been chosen as the underlying layer and var-ious porous matrices in sponge form have been preparedfrom gelatin by freeze-drying technique. [24]. The hae-mostatic effect of gelatin, the wound healing-promotingfeature of alginate and the antiseptic property of boraxhave made the composite matrix based on alginate andgelatin a potential wound dressing material. The pres-ence of dibutyryl cyclic adenosine monophosphate inthe dressing has accelerated healing and re-epithelializa-tion of full-thickness wounds [25,26].

On the other hand, sterculia gum, a medicinally impor-tant naturally occurring polysaccharide, has unique fea-tures such as high swelling and water retention capacity,high viscosity and inherent nature of anti-microbial activ-ity [27]. These features can be exploited for developing thewounds dressing. It has been used to prepare the con-trolled-release matrix and has shown superior muco-adhe-sion than guar gum [28]. Sterculia gum composed ofgalacturonic acid, b-D-galactose, glucuronic acid, L-rham-nose, and other residues [29]. It is obtained from the treeSterculia urens and is commonly known as karaya gum orsterculia gum [27,30].

In view of necessity to develop the biodegradable andbiocompatible wounds dressing, we have exploited thegel forming nature of the sterculia gum which has inherentanti-microbial activity for the development of woundsdressing. The present study is an attempt to synthesizethe novel sterculia gum-PVA composite based polymermatrix for the delivery of antimicrobial agent (tetracyclinehydrochloride). The optimum reaction parameters wereevaluated for the synthesis of sterculia crosslinked PVA(sterculia-cl-PVA) hydrogels by varying the concentrationof crosslinker, plasticizer, sterculia and PVA. The polymermatrix was characterized by FTIR and swelling studies.For the evaluation of swelling and drug release mechanismfrom the matrix, the swelling kinetics of the polymer ma-trix and in vitro release dynamics of model drug from thismatrix were studied in solution of different pH and simu-lated wounds fluid.

2. Experimental

2.1. Materials and methods

Polyvinyl alcohol (PVA) was obtained from HimediaLaboratories Pvt. Ltd., Mumbai, India. Glutaraldehyde(GA) was obtained from S.D.fine-Chem. Ltd., Mumbai,India. Di-n-butylphthalate (DBP) was obtained from MerckPvt. Ltd., Mumbai, India. Tetracycline hydrochloride wasobtained from Nicholas India Ltd., Ahmedabad, India.Sterculia gum was obtained from herbal medical store.Sterculia gum is the dried exudate obtained from trees ofSterculia species which is a large, bushy deciduous tree thatcan grow up to 15 m high. It is found on the dry, rocky hillsand plateaus of central and Northern India. Mostly, it isIndian origin, although increasing amounts come fromAfrica. The chemical composition of gum samples obtainedfrom different Sterculia species and from different placesof origin has been found to be quite similar.

2.2. Synthesis of sterculia-cl-PVA polymer matrix

Solutions of definite concentration of PVA and sterculiagum (w/v) were prepared separately with constant stirringin the beakers. 5 mL of sterculia gum suspension wasadded to the 5 mL PVA solution with constant stirringand after that 100 lL of DBP was added into it at40 ± 2 �C and reaction mixture was stirred for half an hourto get a homogeneous mixture. After that reaction systemwas kept for half an hour at room temperature and to thismixture definite amount of GA was added with constantstirring at room temperature. The mixture was spread inthe 20 mL Petri dish which was kept in oven at 40 ± 2 �Cfor 24 h .The polymer matrix then kept in distilled waterfor 2 h to remove the unreacted GA, sterculia and PVA.The crosslinked product was named as sterculia-cl-PVAcomposite polymer matrix. It was dried at 40 ± 2 �C for12 h. The optimum reaction parameters for synthesis ofsterculia-cl-PVA were evaluated on the basis of the swell-ing, by varying the concentration of crosslinker GA (from1 to 5 mL), plasticizer DBP (from 1000 to 500 lL), 5 mLsterculia (from 0.5% to 2.5%) and 5 mL PVA (1–5%). Allthe reaction parameters for the evaluation of the optimumreaction conditions are presented in the Table 1.

2.3. Characterization of polymeric matrix

Polymeric matrix was characterized by Fourier trans-form infrared spectroscopy (FTIR) and by swelling studies.FTIR spectra were recorded in KBr pellets on NICOLET 5700FTIR system. Swelling kinetics was carried out in distilledwater in triplicate by gravimetric method. Known weightof polymers was taken and was immersed in solvent at37 �C. After 30 min, the polymer was removed, wiped withtissue paper to remove excess of solvent, and weighedimmediately. The equilibrium percent swelling (Ps) of thepolymers was calculated as

Ps ¼ ðWs �WdÞ=Wd � 100

where Ws is the weight of swollen polymer and Wd is theweight of dried polymers. Swelling of the polymers was

Table 1Reaction parameters for the synthesis of sterculia-cl-PVA composite polymer matrixa

S.No. GA25%(ml) Plasticizer(ll) PVA% (w/v)(5 mL)

Sterculia %(w/v)(5 mL)

Amount of water uptakeafter 24 h

Diffusionexponent ‘n’

Gel characteristicconstant‘k’ � 103

1 1 100 5 1 15.66 ± 2.87 0.81 11.592 2 100 5 1 24.39 ± 7.54 0.75 6.273 3 100 5 1 25.79 ± 0.51 0.65 4.424 4 100 5 1 16.52 ± 3.20 0.72 8.855 5 100 5 1 2.99 ± 0.77 0.54 32.666 3 100 5 1 25.79 ± 0.51 0.65 4.427 3 200 5 1 15.88 ± 0.33 0.56 30.488 3 300 5 1 14.85 ± 0.26 0.59 24.59 3 400 5 1 14.29 ± 0.31 0.56 28.97

10 3 500 5 1 10.67 ± 0.19 0.52 43.0011 3 100 1 1 19.22 ± 0.19 0.81 11.512 3 100 2 1 19.67 ± 0.17 0.75 4.9813 3 100 3 1 20.33 ± 0.17 0.65 14.5214 3 100 4 1 24.11 ± 0.25 0.71 8.8515 3 100 5 1 25.79 ± 0.51 0.65 4.4216 3 100 5 0.5 16.46 ± 0.07 0.96 11.5917 3 100 5 1 25.79 ± 0.51 0.65 4.4218 3 100 5 1.5 19.46 ± 0.07 0.65 14.5219 3 100 5 2 20.92 ± 0.07 0.72 8.8520 3 100 5 2.5 25.13 ± 0.12 0.54 32.65

a Glutaraldehyde = ga, reaction temperature = 40 ± 20c; reaction time = 36 h.

3224 B. Singh, L. Pal / European Polymer Journal 44 (2008) 3222–3230

studied as a function of various reaction parameters, as afunction of different pH buffer and simulated wound fluid.

2.4. Release dynamics of the drug

2.4.1. Preparation of calibration curvesCalibration curves of tetracycline HCl were prepared by

using UV–visible Spectrophotometer (Cary 100 Bio, Varian)at wavelength 357, 357 and 361 nm, respectively, in dis-tilled water, pH 2.2 buffer and pH 7.4 buffer solution.

2.4.2. Drug loading to the polymeric membraneThe loading of a drug into the membrane was carried

out in triplicate during the synthesis of the membranesas mentioned in the Section 2.2.

2.4.3. Drug release from polymer matrixIn vitro release of the drug was carried out in triplicate

by placing dried and loaded sample in definite volume ofreleasing medium at 37 �C temperature. The amount of tet-racycline HCl released was measured spectrophotometri-cally by taking the absorbance of the solution after every30 min in solution of different pH and simulated woundsfluid. The drug release was measured after fixed intervalof time and release dynamics of model drugs were studied.

2.4.4. Preparation of buffer solutionBuffer solution of pH 2.2 was prepared by taking 50 mL

of 0.2 M KCl and 7.8 mL of 0.2 N HCl in volumetric flask tomake volume 200 ml with distilled water. Buffer solutionof pH 7.4 was prepared by taking 50 mL of 0.2 M KH2PO4

and 39.1 mL of 0.2 N NaOH in volumetric flask to make vol-ume 200 ml with distilled water [31].

2.4.5. Preparation of pseudo extracellular fluid (PECF)Pseudo extracellular fluid (PECF) that is simulated

wound fluid was prepared, by dissolving 0.68 g of NaCl,

0.22 g of KCl, 2.5 g of NaHCO3, and 0.35 g of NaH2PO4 in100 mL of distilled water. The pH of simulated wound fluidwas observed 8 ± 0.2 [32,33].

2.5. Mechanism of swelling and drug release from polymermatrix

The diffusion of water molecule and drug from thehydrogels has been classified into three different typesbased on the relative rates of diffusion and polymer relax-ation [34,35]. In the case of water uptake, the weight gain,Ms, is described by the following empirical equations:

MS ¼ ktn ð1Þ

where k and n are constant. Normal Fickian diffusion ischaracterized by n = 0.5, while Case II diffusion by n = 1.0.A value of n between 0.5 and 1.0 indicates a mixture ofFickian and Case II diffusion, which is usually called non-Fickian or anomalous diffusion. Ritger and Peppas showedthat the above power law expression could be used for theevaluation of drug release from swellable systems. In thiscase, Mt/M1 replaces Ms in Eq. (1) as shown below

Mt

M1¼ ktn ð2Þ

where Mt/M1 is the fractional release of drug at time t, ‘k’is the constant characteristic of the drug-polymer system,and ‘n’ is the diffusion exponent characteristic of the re-lease mechanism. For cylindrical shaped hydrogels theintegral diffusion is given in simple Eq. (3) by Ritger andPeppas [34,35].

Mt

M1¼ 4

Dt

pl2

� �0:5

ð3Þ

where (Mt/M1) is fractional drug release, Mt is the amountof drug release in time ‘t’ and M1 is the amount of drug re-lease after 24 h. D is diffusion coefficient and l is thickness

B. Singh, L. Pal / European Polymer Journal 44 (2008) 3222–3230 3225

of the hydrogel sample. The average diffusion coefficientDA was calculated for 50% of the total release by puttingMt/M1 = 0.5 in the Eq. (3), which finally yields (4)

DA ¼0:049l2

t1=2 ð4Þ

where t1/2 is the time required for 50% release of drug. latediffusion coefficients were calculated using the late-timeapproximation as described by Peppas given in Eq. (5).

Mt

M1¼ 1� 8

p2

� �exp

ð�p2DtÞl2

� �ð5Þ

The values of diffusion exponent ‘n’ gel characteristic con-stant ‘k’ and various diffusion coefficients for the swellingand drug release dynamics were evaluated and resultsare presented in Table 1–3.

3. Results and discussion

Further polymer matrixes were synthesized at the opti-mum reaction conditions and were characterized by FTIRand swelling studies. These hydrogels were used to studythe swelling kinetics and release dynamics of drug in dif-ferent pH buffer and simulated wounds fluid.

3.1. Characterization

3.1.1. Fourier transform infrared spectroscopy (FTIR)Sterculia-cl-PVA matrix was characterized by FTIR and

swelling studies. FTIR spectra of PVA, Sterculia and stercu-lia-cl-PVA are presented in Fig. 1. In the case of sterculiagum, a broad band at 3425 cm�1 is due to the presenceof �OH of glactopyranose and glucopyranose ring and aband at 1619 cm�1 due to the presence of carboxylategroup of glucouronic acid and glactouronic acid have beenobserved. In case of PVA, a broad band observed at3430 cm�1 is due to the �OH stretching vibrations,

Table 2Results of diffusion exponent ‘n’, gel characteristic constant ‘k’ and various diffusionmatrix in different swelling medium at 37 �C

Swelling medium Diffusion exponent ‘n’ Gel characteristic constan

Distilled water 0.65 14.52pH 2.2 1.0 1.51pH 7.4 1.0 1.75Simulated wounds fluid 1.0 16.87

Table 3Results of diffusion exponent ‘n’, gel characteristic constant ‘k’ and various diffusionpolymer matrix in different medium at 37 �C

Swelling medium Diffusion exponent ‘n’ Gel characteristic constan

Distilled water 0.94 4.76pH 2.2 0.77 11.88pH 7.4 0.99 3.59Simulated wounds fluid 0.84 7.67

whereas the band at 1264 cm�1 is due to the �OH bendingvibration have been observed. In the spectra of crosslinkedproduct that is sterculia-cl-PVA polymer matrix, the smallchange in percent transmittance has been observed ascompared to the spectra of PVA and sterculia. In stercu-lia-cl-PVA the broad band at 3415 cm�1 due to associationin hydrogen bonding, bands at 2927 and 2856 cm�1,respectively, due to asymmetric and symmetric stretchingvibrations of CH2 and corresponding bending vibration at1456 cm�1 and 1379 cm�1 have been observed.

3.1.2. Swelling kinetics of sterculia-cl-PVASwelling behavior of sterculia-cl-PVA was studied as a

function of glutaraldehyde (GA), plasticizer (DBP), polyvi-nyl alcohol (PVA) and sterculia gum. Swelling was alsotaken in solution of different pH buffer and simulatedwounds fluids.

3.1.2.1. Swelling as a function of crosslinker contents. The ef-fect of crosslinker concentration used during the synthesisof sterculia-cl-PVA polymer matrix on the swelling of thematrix was studied by varying the glutaraldehyde contentsfrom 1 mL to 5 mL and results are presented in Fig. 2. It isclear from the figure that swelling of polymer matrix de-creases with increases the crosslinker concentration in thefeed. This is probably due to the reason that increases in glu-taraldehyde contents in the composition of the membraneincreases the crosslinking between the polymer chainswhich causes an increase in the retractive force in the net-work. The maximum amount of water uptake(25.79 ± 0.51) g has been observed in case of the polymermatrix prepared with 3 mL of glutaraldehyde. This concen-tration of the crosslinker was taken as the optimum concen-tration for the synthesis of the wounds dressing. The valuesof diffusion exponent ‘n’ and gel characteristics constant ‘k’have been evaluated from the slope and intercept of the plotln Mt/M1 versus lnt and results are presented in Table 1. Thevalues of ‘n’ are between 0.5 and 1 which indicate non-

coefficients for the swelling kinetics of sterculia-cl-PVA composite polymer

t ‘k’ � 103 Diffusion coefficients (cm2/min)

Initial Di � 104 Average DA � 104 Late time DL � 104

51.30 58.41 7.0739.52 39.23 4.6428.17 25.90 3.2486.70 66.10 13.5

coefficients for the release of tetracycline from drug loaded sterculia-cl-PVA

t ‘k’ � 103 Diffusion coefficients (cm2/min)

Initial Di � 104 Average DA � 104 Late time DL � 104

146.90 75.83 21.84101.99 61.03 18.65

71.81 36.31 9.7393.50 57.97 12.27

(a)

(b)

(c)

627.

7

1023

.5

1264

.0

1461

.1

1637

.417

43.5

2854

.129

24.1

3430

.9

**pva

40

60

80

%T

602.

7

911.

110

41.711

51.6

1256

.313

78.7

1426

.2

1619

.217

36.4

2927

.0

**ster

40

60

80

%T

609.

1

852.

7

1074

.511

23.5

1282

.613

79.1

1456

.9

1652

.817

30.0

2364

.9

2856

.729

27.0

3415

.63743

.138

62.2**str-pva

40

60

80

%T

500 1000 1500 2000 2500 3000 3500 4000 Wavenumbers (cm-1)

Fig. 1. FTIR spectra of (a) PVA (b) sterculia gum (c) sterculia-cl-PVA composite polymer matrix.

3226 B. Singh, L. Pal / European Polymer Journal 44 (2008) 3222–3230

Fickian type of diffusion mechanism for the swelling of ma-trix prepared with different crosslinker contents.

3.1.2.2. Swelling as a function of plasticizer contents. In or-der to evaluate the optimum plasticizer (DBP) concentra-

30 60 90 120 150 180 210 240 270 300 14400

5

10

15

20

25

30

Amou

nt o

f wat

er u

ptak

e pe

r gra

m o

f gel

(g)

Time (min.)

1ml 25% GA 2ml 25% GA 3ml 25% GA 4ml 25% GA 5ml 25% GA

Fig. 2. Effect of glutaraldehyde contents on swelling kinetics of sterculia-cl-PVA composite polymer matrix in distilled water at 37 �C. [Reactiontime = 36 h, temperature = 40 �C, sterculia (1%) = 5 mL, PVA (5%) = 5 mL,DBP = 0.1 mL].

tion for the synthesis of sterculia-cl-PVA, the swellingwas taken for the polymers prepared with different con-centration of plasticizer. The results are presented in theFig. 3. From the figure it is clear that amount of plasticizerin the polymer affects the swelling and trends show that

30 60 90 120 150 180 210 240 270 300 14400

5

10

15

20

25

Amou

nt o

f wat

er u

ptak

e pe

r gra

m o

f gel

(g)

Time (min.)

0.1 mL DBP 0.2 mL DBP 0.3 mL DBP 0.4 mL DBP 0.5 mL DBP

Fig. 3. Effect of plasticizer on swelling kinetics of sterculia-cl-PVAcomposite polymer matrix in distilled water at 37 �C. [Reaction time = 36 h,temperature = 40 �C, sterculia (1%) = 5 mL, PVA (5%) = 5 mL, GA = 3 mL].

B. Singh, L. Pal / European Polymer Journal 44 (2008) 3222–3230 3227

swelling decreases with increase in the plasticizer concen-tration in the polymer composition. This is probably due tothe reason that plasticization occur when plasticizer mole-cules interact with the polar groups of the polymers andreplace the polymer–polymer interactions with plasticizerpolymer interactions thus shielding the polymer chainsfrom interacting with each other and with the water mol-ecules. On the other hand non-polar groups present in theplasticizer also contribute in reducing the same interac-tions in the chains [36]. Plasticizer physically bound tothe gel which is also responsible for the same affect. Max-imum water uptake (25.79 ± 0.51) g/g of polymer matrixhas been obtained when the matrix was prepared with0.1 mL of plasticizer. The values of diffusion exponent ‘n’and gel characteristics constant ‘k’ have been evaluatedand results are presented in Table 1.

3.1.2.3. Swelling as a function of PVA contents. The differentPVA contents in the composition of matrix affect the swell-ing of sterculia-cl-PVA polymers. Swelling increases withincrease in the PVA in the matrix (Fig. 4). It is due to thehydrophilic nature of the PVA, so increase in the contentsof PVA in the matrix increases its hydrophilicity, whichincreases water uptake. This can also be explained on thebasis of the fact that that the polymers were prepared witha constant crosslinker amount while increasing theamounts of PVA, this would result in a lower percentageof crosslinker in the formulation and ultimately provideanother reason for the increase in swelling, and, namely,the decrease in crosslink density. Maximum water(25.79 ± 0.51) g has been taken by polymer matrix pre-pared with 5% (w/v) of PVA solution. The values of ‘n’ arebetween 0.5–1 which indicate that non-Fickian type of dif-fusion mechanism occur in this case (Table 1).

3.1.2.4. Swelling as a function of sterculia contents. Effect ofsterculia gum on water uptake of sterculia-cl-PVA polymermatrix was studied after preparing it with different stercu-

30 60 90 120 150 180 210 240 270 300 1440

2468

10121416182022242628

Amou

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f wat

er u

ptak

e pe

r gra

m o

f gel

(g)

Time (min.)

1% PVA (5 mL) 2% PVA (5 mL) 3% PVA (5 mL) 4% PVA (5 mL) 5% PVA (5 mL)

Fig. 4. Effect of PVA contents on swelling kinetics of sterculia-cl-PVAcomposite polymer matrix in distilled water at 37 �C. [Reactiontime = 36 h, temperature = 40 �C, sterculia (1%) = 5 mL, GA = 3 mL,DBP = 0.1 mL].

lia percentage and amount of water uptake by the polymerat 37 �C is shown in Fig. 5. It is observed from the figurethat amount of water uptake by per gram of polymeric ma-trix increases with increase in the percentage of sterculiagum in polymeric membrane. This is probably due to thereason that higher degree of gum hydration has occurredwhich has increased the number of intimate contactsbetween particle of gum and water and led to high swell-ing [37]. This can also be explained on the basis of similarexplanation given in the effect of PVA. As the polymerswere prepared with a constant crosslinker amount whileincreasing the amounts of sterculia, this would result in alower percentage of crosslinker in the formulation andultimately provide another reason for the increase inswelling, and, namely, the decrease in crosslink density.The total water uptake after 24 h swelling has beenobserved (25.13 ± 0.12) g for the matrix prepared with2.5% (w/v) of sterculia gum solution. The values of diffu-sion exponent ‘n’ and gel characteristics constant ‘k’ arepresented in Table 1.

3.1.2.5. Swelling as a function of pH. The water uptake bythe sterculia-cl-PVA was studied after fixed interval of30 min in distilled water, pH 2.2 buffer and pH 7.4 buffersfor 24 h at 37 �C (Fig. 6). It is observed from the figure thatamount of water uptake by per gram of polymer increaseswith increase in time and amount of water uptake hasbeen observed more in distilled water than pH 7.4 andpH 2.2 buffer solution. Maximum water uptake by pergram of the polymer in distilled water, pH 2.2 buffer andpH 7.4 buffer has been obtained (25.79 ± 0.51) g,(16.11 ± 0.18) g and (15.01 ± 0.24) g, respectively. The val-ues of diffusion exponent ‘n’ and gel characteristics con-stant ‘k’ for the swelling of polymer in different pHsolution have been evaluated from the slope and interceptof the plot of ln Mt/M1 versus lnt and results are presentedin Table 2. It is clear from the table that values of the ‘n’ fordistill water, pH 2.2, pH 7.4 are 0.65, 1.0, and 1.0, respec-

30 60 90 120 150 180 210 240 270 300 14402468

10121416182022242628

Amou

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r gra

m o

f gel

(g)

Time (min.)

0.5% Sterculia (5 mL) 1.0% Sterculia (5 mL) 1.5% Sterculia (5 mL) 2.0% Sterculia (5 mL) 2.5% Sterculia (5 mL)

Fig. 5. Effect of sterculia contents on swelling kinetics of sterculia-cl-PVAcomposite polymer matrix in distilled water at 37 �C. [Reactiontime = 36 h, temperature = 40 �C, PVA (5%) = 5 mL, GA = 3 mL,DBP = 0.1 mL].

30 60 90 120 150 180 210 240 270 300 14400

5

10

15

20

25

30Am

ount

of w

ater

upt

ake

per g

ram

of g

el (g

)

Time (min.)

Distilled waterpH2.2 bufferpH7.4 buffer

Fig. 6. Effect of pH on swelling kinetics of sterculia-cl-PVA compositepolymer matrix at 37 �C. [Reaction time = 36 h, temperature = 40 �C,sterculia (2.5%) = 5 mL, PVA (5%) = 5 mL, GA = 3 mL, DBP = 0.1 mL].

30 60 90 120 150 180 210 240 270 300 1440

1

2

3

4

5

6

7

8

9

Amou

nt o

f sim

ulat

ed fl

uid

upta

ke

per g

ram

of g

el (g

)

Time (min.)

Fig. 7. Swelling kinetics of sterculia-cl-PVA composite polymer matrix insimulated fluid at 37 �C. [Reaction time = 36 h, temperature = 40 �C,sterculia (2.5%) = 5 mL, PVA (5%) = 5 mL, GA = 3 mL, DBP = 0.1 mL].

30 60 90 120 150 180 210 240 270 300 14400

1

2

3

4

5

Amou

nt o

f dru

g re

ales

e (m

g/10

mL

per g

.of g

el)

Time (min.)

Distilled waterpH2.2 bufferpH7.4 buffer

Fig. 8. Release profile of tetracycline HCl from drug loaded polymermatrix of sterculia-cl-PVA in different medium at 37 �C. [Reactiontime = 36 h, temperature = 40 �C, sterculia (2.5%) = 5 mL, PVA (5%) =5 mL, GA = 3 mL, DBP = 0.1 mL, TC solution (2 mg/mL) = 1 mL].

3228 B. Singh, L. Pal / European Polymer Journal 44 (2008) 3222–3230

tively, which indicate that non-fickian type of diffusionmechanism occurred for the diffusion of water in polymermatrix in distilled water and case II mechanism occurredfor the diffusion of water in pH 2.2 and pH7.4 buffer. Thevalues of the diffusion coefficients are presented in theTable 2. The values of initial (Di) and average (DA) diffusioncoefficient have been obtained higher than late diffusioncoefficient (DL). It means that in the initial stages the rateof diffusion of water was higher than the later stages. Inthe start the diffusion of water molecules occurs whichhas started the relaxation of polymer chains and causesthe faster swelling but in the later stages swelling equilib-rium was established which has decreased the rate ofswelling.

3.1.2.6. Swelling of polymer matrix in simulated woundsfluid. The amount of simulated wounds taken by sterculia-cl-PVA was studied in order to see the viability of thesepolymers for use as wounds dressing and swelling kineticswere studied in simulated wounds fluid after fixed intervalof 30 min up to 300 min. The results are presented in Fig. 7.It is observed from the figure that amount of fluid uptakeby per gram of polymer matrix is less as compared to theamount of water uptake by the matrix. Maximum(8.30 ± 0.10) g fluid has been taken by the per gram ofthe polymers. The value of diffusion exponent ‘n’ has beenobserved 1 in simulated fluid which indicates the Case IItype of diffusion mechanism for the swelling of in polymermatrix in simulated fluid (Table 2). Case II diffusion occurswhen diffusion is very rapid compared with relaxation pro-cess. In this mechanism, diffusion of solvent through thepreviously swollen shell is rapid compared with the swell-ing induced relaxation of polymer chains. The values of thediffusion coefficients are presented in the Table 2.

3.2. Release dynamics of the drug

The effect of pH on the release pattern of tetracyclinehydrochloride was studied by varying the pH of the release

medium. The release profile of drug from per gram of thedrug loaded polymer matrix is shown in Fig. 8. Amountof drug released from the matrix has been observed higherin distilled water than that of pH 7.4 buffer and pH 2.2 buf-fer. Fifty percentage of total release of drug in distilledwater, pH 7.4 buffer, pH 2.2 buffer occurred in 131 min,136 min, 121 min, respectively. Maximum (4.50 ± 0.45)mg/g of the polymer matrix has occurred in distilled waterafter 24 h. Release of water soluble drugs, entrapped in themembrane, occur only after water penetrate into poly-meric network which get swell and dissolve the drug, fol-lowed by diffusion along the aqueous pathway to thesurface of device. The release of drug is closely related toswelling characteristics of the polymer matrix, which inturn a, key function of chemical architecture of the poly-meric membrane. Further, in the present case the releaseprofile is corresponding to the swelling pattern. The values

B. Singh, L. Pal / European Polymer Journal 44 (2008) 3222–3230 3229

of diffusion exponent ‘n’ and gel characteristics constant ‘k’for the release of drug from polymer matrix in different pHhave been evaluated from the slope and intercept of theplot ln Mt/M1 versus lnt and result are presented in Table3. It is clear from the table that values of the ‘n’ in all thethree medium showing non-Fickian type of diffusionmechanism. In non-Fickian diffusion the rate of diffusionof drug from the polymer matrix is comparable to rate ofpolymer chain relaxation. The values of diffusion coeffi-cient for the release of drug from the polymer matrix inthe different pH buffer are presented in the Table 3. It isclear from the table that the values obtained for the initialdiffusion coefficient (Di) and average diffusion coefficient(DA) are higher than the late diffusion coefficient (DL). Itmeans that in the starting the rate of diffusion of tetracy-cline hydrochloride was higher than the later stages. Asthe rate of release of drug molecules from the polymersis dependent on the swelling and hence initial higher rateof drug release can be explained on the basis of rate ofswelling. In the start the diffusion of water molecules oc-curs which has started the relaxation of polymer chainsand causes the faster swelling but in the later stages swell-ing equilibrium was established which has decreased therate of swelling.

3.3. Release dynamics of the drug in simulated wounds fluid

In the present studies, the release pattern of tetracy-cline hydrochloride was also studied in simulated woundsfluid and results are presented in Fig. 9. Amount of drug re-leased from the polymer matrix has been observed lowerin simulated fluid than distilled water, pH 7.4 buffer andpH 2.2 buffer. Fifty percentage of total release of drug insimulated fluid occurred in 138 min. The value of the ‘n’in simulated medium has been observed 0.84 which indi-cates the non-Fickian diffusion mechanism for the releaseof drug in simulated fluids. Non-Fickian diffusion occurswhen the rate of diffusion of drug molecules from the poly-

30 60 90 120 150 180 210 240 270 300 14400.0

0.2

0.4

0.6

0.8

1.0

Amou

nt o

f dru

g re

ales

e (m

g/5m

L pe

r g.o

f gel

)

Time (min.)

Fig. 9. Release profile of tetracycline HCl from drug loaded polymermatrix of sterculia-cl-PVA in simulated fluid at 37 �C. [Reactiontime = 36 h, temperature = 40 �C, sterculia (2.5%) = 5 mL, PVA(5%) = 5 mL, GA = 3 mL, DBP = 0.1 mL, TC solution (2 mg/mL) = 1 mL].

mer matrix and rate of relaxation of polymer chains arecomparable. In this diffusion mechanism drug release de-pends on two simultaneous rate processes, water migra-tion into the device and drug diffusion throughcontinuously swelling hydrogels is highly complicated[34,35]. The values of diffusion coefficient are presentedin Table 3 which have been observed lesser than the solu-tion of different pH buffer.

4. Conclusion

It is concluded from the foregone discussion that thecomposition of the polymer matrix and nature of theswelling medium affect the swelling of the polymer ma-trix. Swelling increases with increase in the sterculia andPVA contents in the matrix and it decreases with increasein the crosslinker and plasticizer concentration in the com-position. It is further concluded that the release of drugfrom the polymer matrix dependents upon the nature ofthe release medium and is correlated to the swelling pat-tern of the matrix. The non-Fickian diffusion mechanismhas occurred for the release of drug in simulated woundsfluids. From the swelling and release profile, it may be pro-posed that this matrix can be used for wound dressingafter loading with the antimicrobial agent. This woundsdressing could have the double potential action, first dueto inherent antimicrobial nature of the sterculia gum andsecond due to the controlled release of antimicrobial agentfrom the hydrogel matrix in the controlled and sustainedmanner.

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