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NIM B
Beam Interactions
with Materials & Atoms
Nuclear Instruments and Methods in Physics Research B 266 (2008) 2009–2020
www.elsevier.com/locate/nimb

Development of novel hydrogels by modification of sterculia

gum through radiation cross-linking polymerization
for use in drug delivery
Baljit Singh *, Manu Vashishtha
Department of Chemistry, Himachal Pradesh University, Shimla – 171005, India

Received 29 January 2008

Available online 18 March 2008

Abstract

In order to modify the sterculia gum polysaccharide, to develop the hydrogels meant for the drug delivery, we have prepared sterculia
gum, 2-hydroxyethylmethacrylate (HEMA) and acrylic acid (AAc) based hydrogels by radiation-induced crosslinking polymerization.
Polymeric networks (hydrogels) thus formed were characterized with SEMs, FTIR,TGA and swelling studies which were carried out
as a function monomers concentration, radiation dose, amount of sterculia contents in the polymer matrix and nature of the swelling
medium. This paper discusses the swelling kinetics of the hydrogels and release dynamics of anti-diarrhea model drug ornidazole from
the hydrogels to evaluation of swelling and drug release mechanism. Diffusion exponent ‘n’ have 0.73, 0.56 and 0.61 values and gel char-
acteristic constant ‘k’ have 1.28  102, 2.95  102 and 2.14  102 values in distilled water, pH 2.2 buffer and pH 7.4 buffer. The
release of drug from the polymer matrix occurred through non-Fickian diffusion mechanism. The values for the late time diffusion coef-
ficients have been lower than the values of initial and average diffusion coefficients. It reflects that in the initial stages rate of release of
drug from polymer matrix was higher as compared to the late stages, it means after certain time the drug release occurred in controlled
manner.
Ó 2008 Elsevier B.V. All rights reserved.

Keywords: Radiation-induced cross-linking; Hydrogels; Sterculia gum; Drug delivery

1. Introduction candidate for controlled release of therapeutic agents.

Recently, there has been a rapid growth in the area of
drug discovery, facilitated by novel technologies, which
has resulted in a more urgent focus on developing novel
techniques to deliver these drugs more effectively and effi-
ciently. The ideal pharmacokinetic profile can be achieved
by use of polymer based drug delivery devices. A number
of polymer-based drug delivery devices and carriers have
been proposed for efficient therapy. Among all these drug
delivery devices, hydrogels, specially based on polysaccha-
rides, have attracted considerable attention as excellent
*
Corresponding author. Tel.: +91 1772830944; fax: +91 1772633014.
E-mail address: baljitsinghhpu@yahoo.com (B. Singh).
Hydrogels are three-dimensional polymeric networks
those swell quickly by imbibing a large amount of water
or de-swell in response to changes in their external environ-
ment. These changes can be induced by changing the sur-
rounding pH, temperature, ionic strength and electro
stimulus. The volume phase transitions as a response to dif-
ferent stimuli make these materials interesting objects of
scientific observations and useful materials for use in
advanced technologies [1–3].
Hydrogels can be prepared by radiation-induced cross-
linking polymerization which is carried out by high-energy
radiation like c-radiation in the presence of monomers.
The irradiation of aqueous polymer solution results in
the formation of radicals on the polymer chains. Also, radi-
olysis of water molecules results in the formation hydroxyl

0168-583X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.nimb.2008.03.086
2010 B. Singh, M. Vashishtha / Nucl. Instr. and Meth. in Phys. Res. B 266 (2008) 2009–2020
radicals, which also attack the polymer chains, resulting in
the formation of macro-radicals. Recombination of the
macro-radicals on different chains results in the formation
of covalent bonds and finally a cross-linked structure is
formed [4–6]. The major advantage of this method over
chemical initiation is the production of relatively pure, res-
idue-free hydrogels. Abdel-Aal and coworkers have carried
out graft copolymerization of vinyl monomers onto poly-
saccharides by a simultaneous irradiation technique using
c-rays as the initiator [7]. When grafting has been carried
out by three methods i.e. by using either chemical initia-
tion, or photo-induction or c-radiation-induced polymeri-
zation, higher yields of grafting of HEMA onto chitosan
has been obtained by c-irradiation method [8]. Degree of
grafting increases with increase in irradiation dose and
increase in the monomer concentration. Polymerization
has been controlled by adding homopolymer-inhibiting
agents in the reaction system [9–11]. El-Hag Ali et al. [12]
have carried out the acrylic acid/vinyl sulfonic acid based
copolymerization by using c-radiation and have observed
that the comonomer composition and irradiation dose
affect the swelling property of the hydrogels [12].
The hydrogels based on poly(HEMA) have been pre-
pared through radiation induced polymerization and have
been utilized for the controlled release of antibiotic drugs,
anticancer drugs, peptides and proteins [13–16]. Release of
drugs from the hydrogels depends on their swelling which
is affected by the composition and swelling medium [17].
Incorporation of polysaccharides increases the equilibrium
degree of swelling [18]. The in vitro release dynamics of the
drug from the hydrogels is not only dependent upon the
extent of crosslinking, but also on the amount of drug-
loaded, method of drug loading and pH of the release med-
ium [19,20].
On the other hand sterculia gum is a medicinally impor-
tant naturally occurring polysaccharide composed of
galacturonic acid, b-D-galactose, glucuronic acid, L-rham-
nose and other residues [21]. It exudes from the tree Stercu-
lia urens, belongs to the family ‘Sterculiaceae’ and is
commonly known as karaya or sterculia etc. [22]. Sterculia
gum has unique features such as high swelling and water
retention capacity, high viscosity, inherent nature of anti-
microbial activity and abundant availability [23]. It has
been used in the treatment of diarrhea [24], irritable bowel
syndrome [25], chronic colonic diseases [26] reducing cho-
lesterol and improving glucose metabolism without
adversely affecting most mineral balances [27,28].
Keeping in view, the pharmacological importance of
sterculia gum and drug delivery devices based on hydro-
gels, sterculia gum, if suitably tailored to prepare the
hydrogels, can act as the potential candidates for the novel
drug delivery systems. Modification of the sterculia gum to
develop the hydrogels is not much reported in the literature
and the potential of sterculia gum to develop the drug
delivery systems has not been explored. Therefore, the
present study is an attempt to modify of sterculia gum with
HEMA and AAc through radiation method, for develop-
ing the novel hydrogels for use as drug delivery devices.
The polymeric networks thus formed were characterized
with SEMs, FTIR, TGA and swelling studies. Swelling
behavior of the hydrogels has been studied as a function
of various reaction parameters and, pH and salt concentra-
tion of the swelling media. Swelling kinetics of the hydro-
gels and in vitro release dynamics of model drug from
the drug-loaded hydrogels in different release medium have
been carried out for the evaluation of the mechanism of
swelling and diffusion coefficients.
2. Experimental
2.1. Materials and method
2-Hydroxyethylmethacrylate (HEMA) and acrylic acid
(AAc) were obtained from Merck-Schuchardt, Germany
Ornidazole was obtained from the ARISTO Pharmaceuti-
cals Pvt. Ltd., Mumbai, India. Sterculia gum was obtained
from herbal medical store.
2.2. Synthesis of sterculia-cl-poly(HEMA-co-AAc)
hydrogels by radiation-induced polymerization
Reaction was carried out with 1gram of sterculia gum
and definite concentration of monomers taken 10 mL dis-
tilled water in a test tube. The reaction mixture was irradi-
ated with c-rays in 60Co c-chamber for 24 h with total dose
of 53.14 kGy. The polymers thus formed were stirred for
two hours in 1:1 mixture of distilled water and ethanol to
remove the soluble fractions left in the polymer and were
than dried in oven at 40 °C. These polymers were named
as [sterculia-cl-poly(HEMA-co-AAc)]. The optimum reac-
tion conditions were evaluated for the synthesis of these
polymers by varying [HEMA] (from 0.82  101 to
4.14  101 mol/L), total radiation dose (from 4.42 to
26.52 kGy), [AAc] (from 1.46  101 to 7.29  101 mol/
L) and amount of sterculia from 0.2 g to 1.0 g. The opti-
mum reaction conditions for the synthesis of polymer
matrix through radiation-induced polymerization were
obtained as [HEMA] = 1.64  101 mol/L), radiation
dose = 13.6 kGy, [AAc] = 7.29  101 mol/L) and 0.6 g
sterculia gum (Table 1). At the optimum reaction condi-
tions, further polymers were synthesized and were used to
study the swelling kinetics and release dynamics of drug
from hydrogels in different pH buffer for the evaluation
of swelling mechanism and diffusion coefficients.
2.3. Characterization
Sterculia gum and sterculia-cl-poly(HEMA-co-AAc)
polymers were characterized by the following techniques:
2.3.1. Scanning electron micrography (SEM)
To investigate and compare the surface morphology of
sterculia and sterculia-cl-poly(HEMA-co-AAc), SEMs
were taken on ZEISS EVO 50 Microscope.
 B. Singh, M. Vashishtha / Nucl. Instr. and Meth. in Phys. Res. B 266 (2008) 2009–2020 2011

Table 1
Optimum reaction parameters for the synthesis of sterculia-cl-poly(HEMA-co-AAc) hydrogels (prepare by radiation method)
Serial [HEMA]  101 Total radiation [AAc]  101 Sterculia Amount of water uptake
number (mol/L) dose (kGy) (mol/L) (g) after 24 h. (per g of gel)
1 0.82 53.14 7.29 1 7.28 ± 0.28
2 1.64 53.14 7.29 1 8.79 ± 0.72
3 2.47 53.14 7.29 1 9.27 ± 1.81
4 3.28 53.14 7.29 1 6.90 ± 0.70
5 4.14 53.14 7.29 1 5.93 ± 0.79
6 1.64 4.42 7.29 1 10.21 ± 2.58
7 1.64 8.85 7.29 1 8.91 ± 1.02
8 1.64 13.26 7.29 1 15.04 ± 2.17
9 1.64 17.68 7.29 1 12.06 ± 0.81
10 1.64 22.14 7.29 1 11.05 ± 2.35
11 1.64 26.52 7.29 1 12.59 ± 1.51
12 1.64 13.26 1.46 1 25.15 ± 1.61
13 1.64 13.26 2.91 1 23.32 ± 3.25
14 1.64 13.26 4.37 1 20.46 ± 0.29
15 1.64 13.26 5.83 1 21.56 ± 2.01
16 1.64 13.26 7.29 1 15.04 ± 2.17
17 1.64 13.26 7.29 0.2 14.10 ± 0.76
18 1.64 13.26 7.29 0.4 19.04 ± 1.98
19 1.64 13.26 7.29 0.6 12.84 ± 0.78
20 1.64 13.26 7.29 0.8 12.28 ± 1.47
21 1.64 13.26 7.29 1.0 15.04 ± 2.17

2.3.2. Fourier transform infrared spectroscopy (FTIR)
FTIR spectra of sterculia and sterculia-cl-poly(HEMA-
co-AAc) polymers were recorded in KBr pellets on Nicolet
5700FTIR (THERMO).
2.3.3. Thermogravimetric analysis (TGA)
TGA of sterculia and sterculia-cl-poly(HEMA-co-AAc)
were carried out on a Perkin–Elmer TGA7 in air at a heat-
ing rate of 10 °C/min to examine the thermal properties of
the polymers.
2.4. Swelling studies
Swelling of the polymeric networks was carried out in
triplicate by gravimetric method. Known weight of poly-
mers were taken and immersed in excess of distilled water
for different time intervals at 37 °C and then polymers were
removed, wiped with tissue paper to remove excess of sol-
vent, and weighed immediately. The difference in weight
has given the amount of water uptake by the polymers after
definite time intervals (30 min). The swelling studies were
carried out as a function monomers concentration, radia-
tion dose and amount of sterculia contents in the polymer
matrix. Effect of pH of the swelling medium on swelling
kinetics was studied.
in distilled water, pH 2.2 buffer and pH 7.4 buffer, respec-
tively, and calibration graphs were constructed in each
medium. The concentration of the drug in the sample solu-
tion was read from the graph as the concentration corre-
sponding to the absorbance of the solution.
2.5.2. Drug loading to the polymer matrix
The loading of a drug into polymer networks was car-
ried out by swelling equilibrium method. The polymers
were allowed to swell in the drug solution of known con-
centration for 24 h at 37 °C and than dried, to obtain the
drug-loaded device. The concentration of the rejected solu-
tion was measured to calculate percent entrapment of the
drug in the polymer matrix.
2.5.3. Drug release from polymer matrix
In vitro release studies of the drug were carried out by
placing dried and loaded sample in definite volume of
releasing medium at 37 °C temperature. The amount of
ornidazole released was measured spectrophotometrically.
The release study for model drug was carried out in dis-
tilled water, pH 2.2 buffer and pH 7.4 buffer. The drug
release was measured after fixed interval of time i.e.
30 min up to 300 min and after 24 h and release dynamics
of the model drugs were calculated.

2.5. Release dynamics of the model drug
2.5.1. Preparation calibration curves
In this procedure, the absorbance of a number of stan-
dard solutions of the reference substance at concentrations
encompassing the sample concentrations were measured on
the UV–visible spectrophotometer (Cary 100 Bio, Varian)
at wavelength 318 nm, 316 nm and 318 nm, respectively,
2.5.4. Preparation of buffer solution
Buffer 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
to make volume 200 ml with distilled water. 0.2 M KCl
solution was prepared by dissolving 14.911 g of KCl in dis-
tilled water to make the volume 1000 ml with distilled
water. Buffer solution of pH 7.4 was prepared by taking
50 mL of 0.2 M KH2PO4 and 39.1 mL of 0.2 N NaOH in
2012 B. Singh, M. Vashishtha / Nucl. Instr. and Meth. in Phys. Res. B 266 (2008) 2009–2020

volumetric flask to make volume 200 ml with distilled
water. 0.2 M KH2PO4 was prepared by dissolving
27.218 g. KH2PO4 in distilled water to make volume
1000 ml with distilled water [29].
2.6. Mechanism for drug release from polymer matrix
Based on the relative rate of diffusion of water into poly-
mer matrix and rate of polymer chain relaxation, swelling
of the polymers and the drug release profiles from the
swelling polymers have been classified into three types of
diffusion mechanisms [30,31]. These mechanisms are Case
I or simple Fickian diffusion, case II diffusion and non-Fic-
kian or anomalous diffusion [32,33]. In the case of water
uptake, the weight gain, Ms, is described by the Eq. (1)
M s ¼ ktn ;
where k and n are constants. Normal Fickian diffusion is
characterized by n = 0.5, while Case II diffusion by
n = 1.0. A value of n between 0.5 and 1.0 indicates a mix-
ture of Fickian and Case II diffusion, which is usually
called non-Fickian or anomalous diffusion. Ritger and
Peppas showed that the above power law expression could
be used for the evaluation of drug release from swellable
systems [32,33]. In this case, Mt/M1 replace Ms in above
equation to give Eq. (2). For cylindrical shaped hydrogels,
the initial diffusion coefficients (Di), average diffusion coef-
ficient DA and late diffusion coefficients has been calculated
from the Eqs. (3)–(5), respectively.
Mt
¼ ktn ; ð2Þ
M1
 0:5
Mt Dt
¼4 ; ð3Þ
ð1Þ M1 p‘2

Table 2
Results of diffusion exponent ‘n’, gel characteristic constant ‘k’ and various diffusion coefficients for the swelling kinetics of sterculia-cl-poly(HEMA-co-
AAc) hydrogels (prepared by radiation method)
Serial Parameter Diffusion Gel characteristic Diffusion coefficients (cm2/min)
number exponent ‘n’ constant ‘k’  102 Initial Di  102 Average DA  102 Late time DL  102
Effect of [HEMA]
1 0.82  101 (mol/L) 0.40 5.53 6.03 16.11 1.23
2 1.64  101 (mol/L) 0.43 5.31 8.39 18.88 1.60
3 2.47  101 (mol/L) 0.35 8.84 5.49 16.03 1.21
4 3.29  101 (mol/L) 0.43 4.34 5.19 13.20 1.04
5 4.14  101 (mol/L) 0.40 5.30 6.09 16.09 1.23

Effect of total radiation dose

1 4.42 (kGy) 0.52 3.08 5.59 9.24 0.89
2 8.85 (kGy) 0.52 2.54 4.41 9.26 0.78
3 13.6 (kGy) 0.45 3.95 4.46 10.40 0.85
4 17.68 (kGy) 0.48 3.60 4.53 9.10 0.80
5 22.14 (kGy) 0.52 2.50 4.10 8.68 0.73
6 26.52 (kGy) 0.43 4.32 3.35 8.60 6.55

Effect of [AAc]
1 1.46  101 (mol/L) 0.77 0.64 5.28 7.40 0.74
2 2.91  101 (mol/L) 0.78 0.63 5.97 8.10 0.81
3 4.37  101 (mol/L) 0.71 0.75 3.76 6.93 0.61
4 5.83  101 (mol/L) 0.71 0.63 3.55 7.49 0.61
5 7.29  101 (mol/L) 0.45 3.95 4.46 10.40 0.85

Effect of amount of sterculia

1 0.2 (g) 0.53 2.18 1.42 3.09 0.26
2 0.4 (g) 0.60 1.54 2.39 4.67 0.40
3 0.6 (g) 0.60 1.27 1.75 4.03 0.32
4 0.8 (g) 0.60 1.32 2.69 5.82 0.48
5 1.0 (g) 0.45 3.95 4.46 10.40 0.85

Effect of pH
1 Distilled water 0.45 3.95 4.46 10.40 8.45
2 pH 2.2 buffer 0.52 2.40 7.26 15.67 1.30
3 pH 7.4 buffer 0.58 1.55 4.23 9.31 7.48

Effect of salt
1 Distilled water 0.45 3.95 4.46 10.40 8.45
2 0.9% Nacl 0.56 1.98 6.31 11.88 1.05