Pharmacology & Pharmacy, 2010, 1, 9-17
10.4236/pp.2010.11002 Published Online July 2010 (http://www.SciRP.org/journal/pp)
9
Development and Evaluation of a New
Interpenetrating Network Bead of Sodium
Carboxymethyl Xanthan and Sodium Alginate
for Ibuprofen Release
Rajat Ray, Siddhartha Maity, Sanchita Mandal, Tapan K. Chatterjee, Biswanath Sa
The Division of Pharmaceutics, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Received June 6th, 2010; accepted July 8th, 2010.
ABSTRACT
Interpenetrating network (IPN) beads of sodium carboxymethyl xanthan (SCMX) and sodium alginate (SAL) were pre-
pared by ionotropic gelation process using AlCl3 as a cross-linking agent. The effect of different formula tion variables
like total polymer concentration, gelation time, concentration of cross-linking agent, and drug load on the extent of
release of ibuprofen (IBP), a non stero idal anti-inflammatory drug, was examined. The formation of IPN structure was
examined using Fourier Transform Infra-red (FTIR) analysis and the compatibility of the drug in the bead was evalu-
ated through FTIR, X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) analyses. While increase in
the concentration o f total polymer, gelation time, and drug load decreased the drug release in both acidic (pH-1.2) and
phosphate buffer (PB) solution (pH-6.8), increase in the concentration of cross-linking agent tended to increase the
drug release. However, from all the formulations, the drug release in acidic medium was considerably slow and a
maximum 14% of the loaded drug was released in 2 h. Complete drug release was achieved in PB solution within 210
to 330 min depending upon the formulation variables. The release of the drug followed non-Fickian transport process
in acidic medium and ca se-II transport mechanism in PB solu tion and these release behaviour correlated well with the
kinetics of dynamic swelling of IPN beads. The study indicated that the IPN beads of SCMX and SAL could be a suit-
able dosage form to minimize the drug release in ac idic solution and to con trol the drug release in PB solution depend-
ing upon the need.
Keywords: IPN Bead, Ibuprofen, Drug Release, Kinetics, Swelling
1. Introduction
Among the most abundant natural polymers, polysaccha-
rides are widely used in pharmaceutical dosage forms as
excipients like suspending agents, emulsifying agents,
tablet binders, gelling agents. With the advent of mac-
romolecular chemistry, the use of polysaccharides has
been extended towards new applications in pharmaceuti-
cal, biomedical, and agricultural fields. Although natu-
rally available polysaccharides exhibit certain limitations
in terms of their reactivity and processibility, these can
be overcome by modification of the polysaccharides
through either physical or chemical cross-linking, graft-
ing with other materials and developing hydrogels or
interpenetrating network(IPN) structures.
Since the homopolymers alone can not meet divergent
demand in terms of properties and performances, devel-
opment of IPN appears to be a better approach [1] and
one of the easiest ways for modification of the properties
of polysaccharides. IPN consists of two polymers, each
in network form, which can be cross-linked in the pres-
ence of each other to give a three dimensional network
structure [2] and hence, combine the properties of two
cross-linked polymers in a network form [3]. IPNs are
thus emerging as a rapidly developing branch of polymer
blended technology and are finding applications in artifi-
cial implants, dialysis, membranes, drug delivery systems
[4], and in agricultural field [5].
Sodium alginate (SAL), a hydrophilic biopolymer ob-
tained from brown sea weeds, is a polysaccharide com-
posed of varying proportions of D-mannuronic acid (M)
and L-guluronic acid (G) residues which are arranged in

Development and Evaluation of a New Interpenetrating Network bead of Sodium
Carboxymethyl Xanthan and Sodium Alginate for Ibuprofen Release
10
MM or GG blocks interspersed with MG blocks [6]. Its
unique property of forming water insoluble calcium al-
ginate gel through ionotropic gelation with Ca2+ ions in a
simple and mild condition has made possible to encapsu-
late both macromolecular agents [7] and low molecular
weight therapeutic agents [8,9] in calcium alginate beads.
However in physiological environment, calcium alginate
beads tend to have poor mechanical stability [10]. To
overcome this limitation, IPN beads of SAL with gelatin
or egg albumin [2], polyvinyl alcohol-graftedpolyacry-
lamide [11], N,O-Carboxymethyl chitosan [12] for con-
trolled drug delivery, and with gelatin [5] for controlled
release of pesticides have been developed.
Although xanthan gum, a polysaccharide obtained from
Xanthomonas campestris, can not form gel beads, its
Na-salt of carboxymethyl derivative is able to form gel
beads through ionotropic gelation with Al3+ ions [13].
Sodium carboxymethyl xanthan (SCMX) beads have
been found capable of encapsulating albumin [14] and
diltiazem hydrochloride [15]. However hitherto there are
no reports on IPN beads of SCMX with SAL for drug
release study.
The objective of the present work was to develop a
new IPN bead composed of SCMX and SAL and to eva-
luate the beads for encapsulation and release behavior of
ibuprofen (IBP).
2. Experimental
2.1 Materials
Ibuprofen (Indian Pharmacopoeia) and xanthan gum
were obtained as gift samples from respectively M/S
Albert David Limited and M/S Deys Medical Stores
(Mfg). Pvt. Limited, Kolkata, India. Sodium alginate
(Mol. wt. 240kDa), AlCl3·2H2O (SD Fine Chem Pvt. Ltd,
Mumbai, India), Monochloro acetic acid (Loba Chemie
Pvt. Ltd, Mumbai, India) and all other analytical grade
reagents were obtained commercially and used as re-
ceived.
2.2 Preparation of Sodium Carboxymethyl
Xanthan (SCMX)
Xanthan gum was derivatised to SCMX having
O-carboxymethyl substitution of 0.8 following the me-
thod reported previously [13]. In brief, required amount
of xanthan gum was dispersed in ice cold solution of
45% w/v sodium hydroxide. The dispersion was kept at
5-8°C with continuous stirring for 1h. Monochloroacetic
acid solution (75% w/v) was added with stirring in the
reaction mixture and the temperature was raised slowly
to 15-18°C. After 30 min, the temperature was raised to
75°C and maintained for additional 30 min. The reaction
mixture was, then cooled to room temperature, cut into
small pieces and dried at 50°C. The dried product was
milled, washed with 80% v/v methanol and again dried.
2.3 Preparation of Interpenetrating Network
(IPN) Bead
Required amount of ibuprofen (IBP) was homogenously
dispersed in an aqueous solution of SCMX and SAL. The
resulting dispersion was extruded through 21 G flat-tip
hypodermic needle into AlCl3 solution. Gelation of the
beads was carried out for different periods of time. The
beads were, then collected by filtration, washed with
deionized water, dried at 45°C in a hot air oven to con-
stant weight and kept in a dessicator until used. The
beads were prepared using the following variables:
1) Keeping the drug load constant at 50% w/w of total
polymer and the concentration of AlCl3 constant at 2%
w/v, the total polymer concentration was varied from
2-4% w/v (SCMX to SAL weight ratio 1:1) and the gela-
tion time was varied from 0.5 to 2 hour.
2) Keeping the drug load constant at 50% w/w of total
polymer, the gelation time at 0.5 hour and total polymer
concentration 3% w/v, concentration of AlCl3 was varied
from 2-8% w/v.
3) Keeping the total polymer concentration fixed at
3% w/v, gelation time at 0.5 hour, and AlCl3 concentra-
tion at 2% w/v, drug load was varied from 20-60% w/w
of total polymer. The composition of beads is shown in
Table 1. Each formulation was prepared in duplicate.
Table 1. Composition and drug entrapment efficiency (DEE)
of sodium carboxymethyl xanthan (SCMX) and sodium
alginate (SAL) IPN beads
SCMX%:
SAL%
Drug load
(% w/w of
total polymer)
Gelation
time (hr)
Concentration
of AlCl3
(% w/v )
DEE
(Mean ± SD,
n = 4)
1:1 50 0.5 2 93.46 ± 2.18
1.5:1.5 50 0.5 2 97.22 ± 2.45
2:2 50 0.5 2 99.50 ± 2.86
1:1 50 2 2 91.15 ± 1.92
1.5:1.5 50 2 2 94.25 ± 3.37
2:2 50 2 2 95.31 ± 2.72
1.5:1.5 50 0.5 4 97.25 ± 1.38
1.5:1.5 50 0.5 8 97.65 ± 3.84
1.5:1.5 20 0.5 2 98.86 ± 1.26
1.5:1.5 40 0.5 2 99.16 ± 1.74
1.5:1.5 60 0.5 2 96.96 ± 2.52

Development and Evaluation of a New Interpenetrating Network bead of Sodium
Carboxymethyl Xanthan and Sodium Alginate for Ibuprofen Release
11
2.4 Fourier Transform Infrared (FTIR) Analysis
FTIR spectra of SCMX, SAL and drug free IPN bead
were recorded in a FTIR spectrophotometer (Perkin- El-
mer, model Spectrum RX-1, UK). Each sample was
mixed with KBr and converted into disc at 100 kg pres-
sure using a hydraulic press. The spectra were recorded
within 4000-400 cm-1 wave numbers. Similarly, the FTIR
spectra of IBP and drug loaded IPN beads were recorded.
2.5 Powder X-Ray Diffraction (XRD) Analysis
Qualitative XRD studies were performed using an X-ray
diffractometer (Bruker D8 advanced powder diffracto-
meter, USA). Pure IBP and powdered beads were
scanned from 5° to 55° diffraction angle (2θ) range under
the following conditions:
Source, Ni-filtered Cu-Kα (λ = 1.54) radiation; voltage,
40 kV; Current, 40 mA; scan speed, 16°/min
2.6 Differential Scanning Calorimetry (DSC)
Study
DSC thermograms of IBP and powdered beads were ob-
tained in the following way:
A weighed amount (about 6 mg) of sample was kept in
a hermetically sealed aluminium pan and heated at a scan
speed of 10°C /min over a temperature range of 35°C-
310°C in a Differential Scanning Calorimeter (Perkin-
Elmer, model Pyris Diamond TG/DTA, UK ) which was
calibrated against indium. A nitrogen purge (20 ml/min)
was used throughout the runs.
2.7 Photomicrograph
Photomicrograph of IPN beads were taken at 4X magni-
fication with an optical microscope (Leica DM 2500P)
fitted with a camera (Cannon Power Shot S-80, Japan).
2.8 Drug Entrapment Efficiency
IPN beads (20 mg) were accurately weighed in an elec-
tronic balance (Precisa XB 600 MC, Precisa Instrument
Ltd; Switzerland), immersed in 250 ml USP phosphate
buffer (PB) solution (pH 6.8), and shaken for 2h on a
mechanical shaker. The beads were crushed and further
shaken for 1h. The solution was filtered and an aliquot
following suitable dilution was analyzed at 222 nm in a
UV-Visible spectrophotometer (model Cary-50 Bio-sp-
ectrophotometer, VARIAN, Australia)) and the content
of the beads was determined using a calibration curve
constructed using PB solution of pH 6.8. The reliability
of the above analytical method was judged by conducting
recovery analysis at three levels of spiked drug solution
in the presence or absence of the polymers for three con-
secutive days. The recovery averaged 98.45 ± 2.68%.
DEE was determined using the following relation:
DEE (%) = (Determined drug content/Theoretical drug
content) × 100
2.9 In-Vitro Drug Release Study
In-vitro drug release study was carried out in acidic solu-
tion 0.1 (N) HCl (pH 1.2) and in USP PB solution (pH
6.8) using USP-II dissolution rate test apparatus (model
TDP-06P Electro Lab, Mumbai, India). 20 mg beads
were placed in 500 ml acidic solution or 500 ml PB solu-
tion (37 ± 1°C) and rotated with paddle at 75 rpm. Ali-
quot was withdrawn at different times and replenished
immediately with the same volume of fresh solution.
Undiluted or suitably diluted withdrawn samples were
analyzed spectrophotometrically at 220 nm for acidic
solution and 222 nm for PB solution. The amount of drug
released in acidic solution and PB solution were calcu-
lated from the calibration curves drawn respectively, in
0.1 (N) HCl and PB solution (pH 6.8). Each release study
was conducted four times.
2.10 Swelling Study
Dried drug-free IPN beads (50 mg) were immersed in
25ml acidic solution (pH 1.2) at 37ºC. The beads were
removed at different times by filtration and blotted care-
fully to remove excess surface water. The swollen beads
were weighed. The swelling ratio of the beads were de-
termined using the following formula:
Swelling ratio = (weight of swollen beads-weight of
dry beads)/weight of dry beads
Swelling ratio of the beads in PB solution (pH 6.8)
was determined in a similar way.
2.11 Statistical Analysis
Each formulation was prepared in duplicate, and each
analysis was duplicated. Effect of formulation variables
on drug release was tested for significance level by using
analysis of variance (ANOVA: single factor and two
factor) with the aid of Microsoft® Excel 2003. Differ-
ence was considered significant when p < 0.05.
3. Results & Discussion
3.1 Formation of IPN
IPN beads composed of SCMX and SAL were prepared
by inotropic gelation process using AlCl3 as a common
cross-linking agent for both the polymers. Formulation of
IPN structure was verified by FTIR analysis (Figure 1).
FTIR spectrum of SCMX showed the presence of bands
corresponding to asymmetric and symmetric carboxylate
anions at respectively 1605 cm-1 and 1419 cm-1, a broad
band at 3419 cm-1 corresponding to stretching vibration
of hydroxyl group, a peak at 1327 cm-1 corresponding to
C = O stretching of carboxymethyl group. These results
are similar to the findings reported earlier [14]. The
spectrum of SAL showed the bands characteristics of

Development and Evaluation of a New Interpenetrating Network bead of Sodium
Carboxymethyl Xanthan and Sodium Alginate for Ibuprofen Release
12
Figure 1. FTIR spectra of (a) SCMX, (b) SAL, (c) drug free
IPN bead
asymmetric and symmetric carboxylate anions at respec-
tively 1612 cm-1 and 1420 cm-1, a broad peak corre-
sponding to the stretching of hydroxyl group at 3468
cm-1. Similar spectrum of SAL has been reported else-
where [16]. The FTIR spectrum of drug-free IPN beads
showed peaks at 1639 cm-1 and 1425 cm-1 respectively
for asymmetric and symmetric carboxylate anions and a
peak at 3405 cm-1 for hydroxyl group. Moreover, the
peak at 1327 cm-1 assigned for carboxymethyl group was
retained. Comparison of the spectra, however, demon-
strated shift of the peaks of carboxylate anions to higher
wave numbers. The shift of carboxylate bands confirms
the formation of complex between the two polymers and
Al3+ ions through physical cross-linking. These results
suggest the formation of IPN structure wherein both the
polymers are present in cross-linked condition.
3.2 Morphology of IPN Bead
The composition of IBP-loaded IPN beads has been
shown in Table1. The beads were prepared with a SCMX
to SAL weight ratio of 1:1 but in different total polymer
concentration (1%:1%, 1.5%:1.5%, 2%:2%) and gelling
in AlCl3 solution (2-8% w/v) for different periods of time
(0.5 to 2 h). Although the shapes of the wet beads were
spherical, the shapes distorted after drying. The surface
of dried beads was rough and folded (Figure 2) and was
due to shrinkage of the beads during the drying process.
Similar shape distortion has been reported for chitosan/
Figure 2. Photo micrographs of ibuprofen-loaded IPN
beads, prepared under different conditions. (a) SCMX:
SAL 1%:1%, 2% w/v AlCl3, 0.5 h, (b) SCMX: SAL 1.5%:
1.5%, 4% w/v AlCl3, 2 h, (c) SCMX: SAL 2%:2%, 8% w/v
AlCl3, 0.5 h
carageenan beads [17]. Moreover, neither the concentra-
tion of cross-linking agent (AlCl3) nor the gelation time
had any appreciable effect on morphology of IPN beads.
The shape of the beads did not change even when the
drug load was varied from 20 to 60% w/w of total poly-
mer.
3.3 Compatibility of Drug in IPN Bead
Compatibility of IBP in IPN beads was studied using
FTIR, XRD and DSC analyses. The characteristics bands
corresponding to C=O stretching and –OH stretching of
IBP appeared in FTIR spectrum respectively at 1720 cm-1
and 2956 cm-1. The above two bands were also detected
at the same positions in the spectrum of drug-loaded IPN
beads (Figure 3). XRD analysis showed reflection to the
interplanner distances of 14.41, 7.24, 5.32, 5.01, 4.72,
4.65, 4.39, 3.98 and 3.63 Å respectively at 6.13, 12.21,
16.64, 17.68, 18.78, 19.06, 20.20, 22.30 and 24.52˚ 2θ.
Drug–loaded IPN beads also exhibited the same reflec-
tions at the same 2θ degrees (Figure 4). The result indi-
cates that the crystallinity of the drug in IPN beads was
retained and no amorphization of the drug took place.
Comparison of DSC thermograms revealed that the
Figure 3. FTIR spectra of (a) Ibuprofen (b) Ibupro-
fen-loaded IPN bead
Figure 4. X-ray diffractograms of (a) Ibuprofen (b) Ibupro-
fen-loaded IPN bead

Development and Evaluation of a New Interpenetrating Network bead of Sodium
Carboxymethyl Xanthan and Sodium Alginate for Ibuprofen Release
13
melting endothermic peak of IBP at 79°C also appeared
in the DSC curve of drug loaded IPN bead (Figure 5).
These studies indicated that apparently no interactions
between the drug and the polymers took place during the
formation of IPN beads.
3.4 DEE of IPN bead
DEE of IPN beads tended to increase as the total polymer
concentrations was increased from 2-4% w/w keeping
SCMX to SAL weight ratio constant at 1:1 (Table 1).
Two way analysis of variance (ANOVA-2) revealed sig-
nificant difference (F2,3 > Ftabular at 0.05 level) in DEE in
IPN beads prepared with increasing polymer concentra-
tions although no significant difference was noted within
the batches of each formulation. Same observations were
noted with IPN beads which were prepared by gelling in
0.5% AlCl3 solution for two different gelation times. In-
crease in DEE with increase in total polymer concentra-
tions is related to the higher rigidity of the matrices of
IPN beads. Higher encapsulation efficiency of cefadroxyl
has been reported for IPN beads prepared using SAL and
gelatin or egg albumin [2]. Concentrations of cross-linking
agent did not produce any appreciable change in DEE
of IPN beads prepared with a total polymer concentra-
tion of 3% w/v keeping SCMX to SAL weight ratio
constant at 1:1. The results of one way analysis of vari-
ance (ANOVA-1) revealed no significant difference in
DEE (F2,3 < Ftabular at 0.95 level) of IPN beads prepared
with various concentrations of AlCl3 . Similar independ-
ence of DEE on the extent of cross-linking has been re-
ported for ketorolac loaded IPN beads composed of so-
dium carboxymethyl cellulose and gelatin [18]. The time
of gelation, however, had an impact on DEE which
tended to decrease as gelation time was increased (Table
1). The results are in agreement with the reports of other
workers [2]. Although the solubility of IBP in aqueous
medium is very less, prolonged exposure in the gelation
medium may cause greater leaching of the drug from IPN
beads resulting in decreased DEE. IPN beads having 20
to 60% w/w of IBP were prepared using 3% w/w total
polymer concentration and gelling for 0.5 h in 2% w/v
AlCl3 solution. DEE was found to vary within 96.96 to
99.16% (Table 1). No significant effect of drug loading
on DEE was observed. Similar non-dependence of DEE
on % of drug loading has been reported for IPN beads
composed of sodium carboxymethyl cellulose and gela-
tin.
3.5 In-Vitro Drug Release
3.5.1 Effect of Polymer Concentration
Release of IBP from IPN beads, prepared using increased
polymer concentrations (SCMX: SAL weight ratio 1:1)
and gelling for 0.5 h in 2% AlCl3 solution, have been
represented in Figure 6. Drug release in acidic medium
Figure 5. DSC thermograms of (a) Ibuprofen (b) Ibupro-
fen-loaded IPN bead
Figure 6. Release profiles of Ibuprofen in acidic solution
(open symbols) and phosphate buffer solution (closed sym-
bols) from IPN beads prepared using different concentra-
tion of SCMX and SAL and gelling in 2% w/v AlCl3 solu-
tion for 0.5 h. Key: SCMX: SAL = () 1%:1%, (∆)
1.5%:1.5%, () 2%:2%. Maximum SEM = 1.24(n = 4)
was slow and 8.82 to 14.09% of the loaded drug was
released in 2 h. In PB solution (pH 6.8), complete drug
release was achieved in 210 min to 300 min depending
upon the total polymer concentration in the beads. In-
crease in total polymer concentration from 2 to 4% w/w
decrease the drug release in both the dissolution media.
The derived properties obtained from drug release pro-
files indicated that the area under the curves (AUCs),
determined using trapezoidal rule, in acidic dissolution
medium decreased as the polymer concentration in IPN
beads increased. Similarly, the time required for 50%
(t50%) and 80% (t80%) drug release in PB solution in-
creased and AUCs decreased with increase in polymer
concentration in the beads. Similar trend in drug release
was observed from IPN beads which were prepared by
gelling for 2 h (Table 2). Drug release from hydrophilic
polymeric beads depends upon the type of matrix used as
well as its rigidity [11]. Increase in total polymer con-
centration results in a more entangled or more compact
gel system with a greater cross-linking density in the

Development and Evaluation of a New Interpenetrating Network bead of Sodium
Carboxymethyl Xanthan and Sodium Alginate for Ibuprofen Release
14
Table 2. Derived properties of drug release in different dissolution media from IPN beads prepared using different polymer
concentrations and gelling for 2 h in 2% w/v AlCl3 solution
In acidic solution In phosphate buffer solution
SCMX%:
SAL% AUC (% mg · min/ml)
(Mean ± SD, n = 4)
t50% (min)
(Mean ± SD, n = 4)
t80% (min)
(Mean ± SD, n = 4)
AUC (% mg·min/ml)
(Mean ± SD, n = 4)
1:1 885.6 ± 56.31 94.8 ± 5.20 143.5 ± 15.21 14336.1 ± 25.63
1.5:1.5 729.2 ± 35.50 108.5 ± 8.75 174.1 ± 10.11 12553.9 ± 27.75
2:2 574.5 ± 46.21 132.4 ± 6.31 209.6 ± 8.65 10564.5 ± 14.02
matrix [12]. As a result, the rigidity of gel matrix in-
creases and free volume of the matrix decreases [19].
This hinders easy transport of drug molecules through
the matrix and reduces drug release from the matrix.
3.5.2 Effect of Swelling of IPN Bead
The release of a drug from a polymeric matrix is con-
trolled by the swelling behaviour of the polymer. To
study the effect of swelling of IPN beads on drug release,
swelling ratio of beads was measured in terms of water
uptake at selected time intervals and the results have
been represented in Figure 7. While the swelling ratio of
the IPN beads was very low in acidic solution, the same
property increased considerably in PB solution (pH 6.8).
The main functional group present in both the polymers
that undergoes cross-linking with Al3+ions is –COOH
group. In acidic solution, –COOH group remains proto-
nated and exerts insignificant electrostatic repulsive force.
As a result, the beads swell to very less extent. At higher
pH value of PB solution, –COOH group undergoes ioni-
zation which exerts electrostatic repulsion between the
ionized groups, and results in higher swelling. Moreover,
upon ionization, the counter ion concentration inside the
polymeric network increases, and an osmotic pressure dif-
ference exists between the internal and external solutions
of the beads. The increased osmotic pressure is balanced
by the swelling of the beads [20]. The higher the swelling
of the polymers, the higher is the drug release from the
IPN beads. Thus the slower release of IBP in acidic solu-
tion and faster release in PB solution are related to the
swelling behaviour of IPN beads in the respective disso-
lution media. It was further observed that increase in
total polymer concentration from 2 to 4% w/v decreased
the swelling of IPN beads in both the media. At low po-
lymer concentration, the polymeric network is loose with
a greater hydrodynamic free volume which allows more
of the liquid to be absorbed and produces higher swelling.
This, in turn, facilitates transport of the drug molecule
through the matrix and causes higher drug release [21].
On the other hand, at higher polymeric concentration,
opposite phenomenon takes place resulting in slower
release of drug.
3.5.3 Effect of Concentration of AlCl3
The effect of the concentration of the cross-linking agent
(AlCl3) on the release profiles of the drug was studied
with IPN beads prepared using 3% w/v total polymer
concentration and gelling for 0.5 h in 2-8% AlCl3 solu-
tion. Figure 8 showed that as the concentration of AlCl3
Figure 7. Swelling ratios of IPN beads, in acidic solution
(open symbols) and phosphate buffer solution (closed sym-
bols), prepared using different concentration of SCMX and
SAL and gelling in 2% w/v AlCl3 solution for 0.5 h. Key:
SCMX: SAL = () 1%:1%, (∆) 1.5%:1.5%, () 2%:2%
Figure 8. Release profiles of ibuprofen in acidic solution
(open symbols) and phosphate buffer solution (closed sym-
bols) from IPN beads prepared using SCMX: SAL = 1.5%:
1.5% and gelling for 0.5 h in different concentration of
AlCl3 solution. Key: () 2% w/v, (∆) 4% w/v, () 8% w/v.
Maximum SEM = 0.81 (n = 4)

Development and Evaluation of a New Interpenetrating Network bead of Sodium
Carboxymethyl Xanthan and Sodium Alginate for Ibuprofen Release
15
was increased during the preparation of beads, the release
of drug increased in both the dissolution media. Statisti-
cal analysis in terms of ANOVA-1 also confirmed this
phenomenon as the AUCs in acidic medium increased
and t50%, t80% decreased and AUCs increased in PB solu-
tion significantly. This unusual release behaviour could
be explained in the following way. When the IPN beads
were prepared with higher concentration of AlCl3, a thick
outer gel layer might have been formed along the periph-
ery of the beads. The thicker outer gel layer provided
higher diffusional resistance to further influx of Al3+ ions
resulting in the formation of inhomogeneous gel beads
and less densely cross-linked matrix in the core of the
beads. During dissolution study, once the outer thick gel
layer swelled, quick drug release occurred from the beads.
At lower concentration of AlCl3, Al3+ ions diffuse more
uniformly into the beads and form homogenous gel beads
resulting in slow drug release.
3.5.4 Effect of Gelation Time
The derived properties obtained from drug release pro-
files (Table 3) indicated that increase in gelation time
decreased the drug release appreciably. The higher the
gelation time, the greater is the cross-linking density and
rigidity of the matrix which resulted in a fall in drug re-
lease.
3.5.5 Effect of Drug Load
The effect of drug load on the release dynamics of IBP
was studied using IPN beads prepared using 3% w/v total
polymer concentration (SCMX:SAL in a weight ratio 1:1)
and gelling for 0.5 h in 2% w/v AlCl3 solution, and the
results are shown in Figure 9. Increase in drug load from
20 to 60% w/w of total polymer decreased the drug re-
lease in both the dissolution media. Generally, higher
drug load provides higher concentration gradient be-
tween the drug in the dosage form and the external dis-
solution medium and results in faster drug release. The
release of a drug is governed not only by drug diffusion
through the polymeric network but also by the relaxa-
tional process of the polymer on solvent penetration.
Low drug load in IPN beads forms larger pore fraction
resulting in higher swelling and consequently faster drug
release. On the other hand, at higher drug load, larger
crystalline domain of drug is formed in the beads. This
causes reduction as well as shrinkage of pores of the ma-
trix and results in fall in drug release. Decrease in drug
release with increase in drug load from various IPN
beads have been reported [5,18,22-23].
3.5.6 Release Kinetics
Drug release from a swellable matrix primarily depends
on the degree of gelation, hydration, chain relaxation,
and erosion of polymer. To understand the mode of drug
transport through the IPN beads, the release data were
fitted to the classical power law expression [24]
Mt/Mα = Ktn
where Mt and Mα are, respectively, the amount of drug
released at time t and at infinite time, K represents a con-
stant incorporating structural and geometrical character-
istics of the dosage forms, n denotes the diffusion expo-
nent indicative of the mechanism of drug release. Values
of n ranging from 0.45 to 0.5 indicate Fickian or diffu-
sion controlled release, values of n ranging from 0.5 to
0.89 indicate non-Fickian or anomalous release, and val-
ues of n ranging from 0.89 to 1.0 indicate Case-II trans-
port mechanism. By applying least squares method to
release data, the values of n were estimated and have
been shown in Table 4 along with the correlation
co-efficient (r2). The results indicate that drug release in
acidic medium followed non-Fickian mechanism and in
PB solution drug release occured following case-II tran-
sport mechanism. When the swelling data of drug-free
IPN beads were fitted to the above power law expression,
it was found that swelling in acidic medium took place
following the non-Fickian mechanism and that in PB solu-
tion followed Case-II transport mechanism (Table 4).
Table 3. Effect of gelation time on derived properties of drug release in different dissolution media from IPN beads prepared
using different polymer concentration and gelling in 2% w/v AlCl3 solution for different periods of time
In acidic solution In phosphate buffer solution
Gelation time 0.5 h Gelation time 2 h Gelation time 0.5 h Gelation time 2 h
SCMX%:
SAL% AUC
(% mg · min/ml)
(Mean ± SD,
n = 4)
AUC
(% mg · min/ml)
(Mean ± SD,
n = 4)
t50% (min)
(Mean ± SD,
n = 4)
t80% (min)
(Mean ± SD,
n = 4)
AUC
(% mg · min/ml)
(Mean ± SD,
n = 4)
t50% (min)
(Mean ± SD,
n = 4)
t80% (min)
(Mean ± SD,
n = 4)
AUC
(% mg · min/ml)
(Mean ± SD,
n = 4)
1%:1% 970.1 ± 22.63 885.4 ± 56.31 77.5 ± 7.86111.1 ± 11.5313151.5 ± 31.4694.8 ± 5.20 143.5 ± 15.21 14336.1 ± 25.63
1.5%:1.5% 702.2 ± 27.15 729.2 ± 35.50 94.3 ± 10.45148.1 ± 9.4511117.7 ± 20.46108.5 ± 8.75174.1 ± 10.11 12553.9 ± 27.75
2%:2% 565.5 ± 13.36 574.5 ± 46.21 119.7 ± 12.61176.4 ± 14.639230.4 ± 26.81132.4 ± 6.31209.6 ± 8.65 10564.5 ± 14.02

Development and Evaluation of a New Interpenetrating Network bead of Sodium
Carboxymethyl Xanthan and Sodium Alginate for Ibuprofen Release
16
Table 4. Kinetic data (n) and correlation coefficient (r2) of
(A) drug release and (B) swelling of IPN beads prepared by
gelling in 2% w/v AlCl3 solution for 0.5 h
In acidic solution In phosphate buffer solution
SCMX:SAL
n r2 n r2
1%:1% 0.73 0.997 1.26 0.989
1.5%: 1.5% 0.69 0.996 1.28 0.994
A
2%:2% 0.87 0.993 1.30 0.989
1%:1% 0.69 0.877 1.40 0.996
1.5%:1.5% 0.64 0.935 1.33 0.982 B
2%:2% 0.80 0.907 1.23 0.923
Figure 9. Effect of drug load on release of ibuprofen in
acidic solution (open symbols) and phosphate buffer solu-
tion (closed symbols) from IPN beads prepared using
SCMX:SAL = 1.5%:1.5% and gelling for 0.5 h in 2% AlCl3
solution. Key: drug load, () 20% w/v, (∆) 40% w/v, ()
60%w/v of total polymer. Maximum SEM = 1.27 (n = 4)
4. Conclusions
SCMX-SAL interpenetrating network beads were pre-
pared by inotropic gelation method using Al3+ ions as
cross-linking agent for both the polymers. Formation of
IPN structure was verified by FTIR analysis and the ab-
sence of drug-polymer interaction in IPN beads was con-
firmed by FTIR, XRD, and DSC analysises. DEE of IPN
beads were found to be reasonably high (91.15 to 99.50%)
and was not affected by formulation variables except the
gelation time, the increase of which tended to decrease
DEE. While the release of IBP decreased in both acidic
(pH 1.2) and PB solution (pH 6.8) with increase in total
polymer concentration, gelation time, and drug load, the
drug release increased in both the media with increase in
the concentration of AlCl3. However, all the formulations
showed considerably low release in acidic medium and
the release followed non-Fickian transport mechanism
due to poor swelling of the beads. Complete drug release
was achieved in PB solution (pH 6.8) at different periods
of time depending on the formulation variables and the
release followed case II transport process due to swelling
and erosion of the beads. The results of the study indicate
that high drug-loaded IPN beads can be prepared using
SCMX and SAL by ionotropic gelation process and
could be used to minimize the release of IBP in acidic
medium and to modulate the drug release in PB solution
(pH 6.8).
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