Vol.3, No.11, 955-962 (2011) Natural Science
Copyright © 2011 SciRes. OPEN ACCESS
Influence of coating on the triamcinolone release of
alginate chitosan beads for colonic drug delivery
Nadir Veiga Vier, Ruth Meri Lucinda-Silva*
Programa de Mestrado em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Pharmacy Course,
University of Vale do Itajaí, Itajaí, Brazil; *Corresponding Author: rlucinda@univali.br
Received 9 March 2011; revised 14 May 2011; accepted 15 June 2011.
The aim of this study was to evaluate the effect
of coating of alginate-chitosan (AL:CS) beads
on the colonic drug delivery. The AL:CS sys-
tems containing triamcinolone (TC) were coated
with the HPMCP and Eudragit® L100 by immer-
sion and by spraying methods. The drug release
profile in simulated colonic medium was deter-
mined using 5% human fecal content suspen-
sion in 0.01 N buffer solution, pH 6.8. The sys-
tems coated with HPMCP showed a lower rate of
drug delivery in simulated enteric medium. The
delivery profile in simulated colonic medium
followed zero-order kinetic. The coated systems
provided a promising drug-delivery profile for
application in colonic drug delivery.
Keywords: Alginate; Beads; Chitosan;
Colon-Specific Drug Delivery; Triamcinolone
Colon-specific drug delivery has attracted the atten-
tion of many researchers interested in the treatment of
diseases of that specific location, such as ulcerative coli-
tis and Crohn’s disease, in its potential as a method of
protein and peptide delivery, and in the treatment of cir-
cadian diseases, such as rheumatoid arthritis and bron-
chial asthma [1]. The colon is considered to be an ideal
environment for protein and peptide drug absorption,
due to the low diversity and activity of digestive en-
zymes and to its near neutral pH [2,3].
Colon-specific systems, whose delivery mechanism is
the colonic microflora, can be developed using polysac-
charides [4]. The polysaccharides remain undigested in
the stomach and small intestine, but are degraded by the
anaerobic microflora present in the colon. The use of
polysaccharides in the development of drug-delivery
systems is based on their abundance, as they are very
common, cheap, biodegradable, stable and available in a
wide variety of structures, with, consequently, a wide
variety of physical and chemical properties [5]. Poly-
saccharides such as chitosan (animal), alginate (marine),
pectin (plant), chondroitin sulphate (animal), dextran
(microbial) and guar gum (plant) have been used as car-
riers in colon-specific drug delivery systems [6,7].
Chitosan (CS) is a polymer with a cationic character
found in the cell walls of some fungi, and can also ob-
tained from chitin [8], with applications in the fields of
cosmetics, biotechnology, microbiology, environmental
protection, agriculture, textiles and biomedicine [9,10].
Alginates (AL) are linear water-soluble polysaccha-
rides, which can be extracted from brown algae [8] and
are also present in some bacterial species, such as
Azotobacter vinelandii and several species of Pseudo-
monas [11]. They are copolymers consisting of two
types of uronate residue, mannuronate β-D and α-L
guluronate, joined by a glycosidic link (1,4) [12]. Be-
cause of their various properties, such as immunogenic-
ity, bioadhesion, biocompatibility and biodegradability,
the pharmaceutical, food and cosmetics industries, have
invested in alginate as carrier of therapeutic systems,
including controlled release systems [6,13].
Alginate and chitosan (AL:CS) particles have been
used as carriers for the controlled release of proteins and
drugs as they are biocompatible, biodegradable and mu-
coadhesive [14]. The high hydrophilic properties shown
by polysaccharides in general are the limiting factor for
their individual application in colon-specific drug deliv-
ery systems [15]. However, the combination of polysac-
charide particles with gastro-resistant polymer coatings
can be strategically developed as a tool for controlling
drug delivery, maintaining therapeutic action along the
gastrointestinal tract (GIT), and enabling drug delivery
at the desired target by preventing early swelling and
consequent premature drug delivery in the higher GIT [8].
Polymers derived from cellulose, such as hydroxypropyl
cellulose phthalate and cellulose acetophthalate, and
gastro-resistant film formers like the polymethacrylates,
such as methacrylic derivatives of ethacrylic and methyl
N. V. Vier et al. / Natural Science 3 (2011) 955-962
Copyright © 2011 SciRes. OPEN ACCESS
methacrylic polyacids, such as Eudragit®, are the most
frequently used coatings for this purpose [16,17].
The aim of this study was to determine the effect of two
gastro-resistant polymer coatings, hydroxypropyl cellu-
lose phthalate and Eudragit L100®, for the AL:CS beads,
using different coating methods, on the colon-specific
delivery of triamcinolone, a slightly water-soluble corti-
costeroid used in the treatment of ulcerative colitis.
2.1. Materials
Chitosan was purchased from Purifarma® (Brazil),
Hydroxypropyl methylcellulose phthalate (HPMCP) was
purchased from Sigma® (Brazil), Eudragit® L100 was
purchased from Degussa (Germany), sodium alginate
was purchased from Vetec (Brazil) and triamcinolone
was purchased from Galena (Brazil). All other reagents
used were of analytical grade.
2.2. Preparation of AL:CS Systems
The multiparticulate systems were prepared by the
method of complex coacervation/ionotropic gelation. 1%
sodium AL aqueous dispersion (pH 5.5) containing the
drug (5 mg·mL–1) was dropped into 0.5% CS dispersion
in 0.1 N acetic acid (pH 5.5) containing 1.5% calcium
chloride, using a syringe and needle with a 250 µm di-
ameter. The particles were reticulated, separated by fil-
tering, washed with water and freeze-dried.
The AL:CS systems containing TC were coated using
2 different methods: immersion and spray coating. In the
immersion coating method (IC), particles were sub-
merged in the polymer dispersions and dried in an oven
at 45˚C. The coating materials used were: HPMCP dis-
persions (1%, 5% and 7.5% in acetone:alcohol 1:1) and
a 6.8 pH aqueous solution of 1% Eudragit L100®.
In the spraying coating method (SC), a tablet coating
machine was used. The polymer coating dispersion (1%
Eudragit® L100 or 7.5% HPMCP) was placed under the
dried particles, which were coated using a 2 mL·min–1
spray stream with a pressure of 4 mbar and rotation at 60
rpm. Three layers of the coating were applied in order to
increase the system weight by around 10%.
2.3. Morphological and Granulometric
The morphology of the systems was analyzed by scan-
ning electron microscopy (Phillips XL30) and optical
microscope (Olympus SZPT). In the SEM analysis, the
dried samples were placed on double-sided adhesive
tape attached to a metal support, coated with colloidal
gold under vacuum and analyzed. In the stereoscopic
analysis, the dried particles were placed in glass slides
and analyzed using the software Qwin Leica Image
Analysis Systems.
Granulometric distribution, area and roundness were
assessed by Leica MZ APO stereoscope and Leica Qwin
Image Analysis Systems software. Approximately 400
particles were analysed and their size was determined
using the diameter according to Feret at 0˚.
2.4. Water Uptake and Swelling Ratio
The analysis of water uptake and swelling was evalu-
ated in simulated gastric and intestinal media (0.1 N HCl
pH 1.5 and phosphate buffer pH 7.4). The water uptake
by the systems was determined by gravimetry. The parti-
cles (n = 10) were weighed before and during the 3 h of
contact with the media. The percentage of water uptake
(WU) was calculated using Eq.1, where Wd and Wm are
the dry and moist weights of the systems, respectively.
 
The swelling ratio was determined by diameter in-
crease according to the Feret method (0˚) using stereo-
scopic and image analysis software. Swelling capacity
was related to the increase in particle diameter, measured
individually before and after the contact of the particles
with the different media. The swelling ratio was calcu-
lated by Eq.2, where SR is the swelling ratio, d1 is the
diameter after swelling and d0 is the diameter before
contact with the simulated media.
 
2.5. Determination of Triamcinolone
Content and Entrapment Efficiency
For determination of drug content, approximately 5 mg
of system was placed in contact with 20 mL of phos-
phate buffer 50 mM pH 7.5 for 2 h, under stirring. The
samples were then filtered and the drug quantified by
UV spectrophotometry at 242 nm. Drug content was
calculated using Eq.3, where TE is the drug content, mTC
is the TC weight quantified in the sample and msyst is the
weight of the system in the sample.
% 100
TC syst
TEm m (3)
Entrapment efficiency was calculated from drug con-
tent and capsule yield using Eq.4, where EE is entrap-
ment efficiency, TE is drug content, R is capsule yield in
mass and MTCtotal is the total mass of drug used in the
formulation analyzed.
EETE Rm (4)
N. V. Vier et al. / Natural Science 3 (2011) 955-962
Copyright © 2011 SciRes. OPEN ACCESS
2.6. Drug Release Profile
The assay was performed in a dissolution station using
the basket method, under the following conditions: me-
dium volume of 400 mL, agitation speed of 50 rpm and
temperature of 37˚C ± 0.5˚C. The release media used
were: simulated gastric (2 h) and enteric (4 h) juices
without enzymes. The drug was quantified by UV spec-
trophotometry at 242 nm.
The drug release profile in simulated colonic medium
(SCM) was determined using 5% human fecal content
suspension in 0.01 N buffer solution, pH 6.8. The assay
was performed using 300 mL of medium and agitation of
approximately 70 rpm in an anaerobic environment for
24 h. The anaerobic environment was obtained by the
insufflation of CO2 produced by the reaction of sodium
carbonate (50 g) with sufficient quantity of 2 M sulfuric
acid for saturation of system in a closed environment.
The drug was quantified by HPLC using a reverse-
phase C18 column, UV detection at 242 nm, temperature
at 35˚C, a flow velocity of 1 mL·min–1 and 0.02 M so-
dium acetate (pH 4.8) and acetonitrile (68:32) mobile
phase buffer. Samples were quantified after centrifuga-
tion and membrane filtration at 0.45 µm.
2.7. In Vitro Drug Release Kinetics Analysis
To study the in vitro drug release kinetics, order zero,
first order, Higuchi, Hixon Crowell, Korsmeyer-Peppas
and Baker-Lonsdale mathematical models were used. The
adequacy of the delivery profiles to the mathematical
models was based on the correlation coefficient value [18].
The study was conducted using the software Sigma-
Plot® version 9.0.
The uncoated systems containing TC had a greater
sphericity compared to the coated systems (Figures 1(a)
and (b)). For the coated systems, it was observed that
those coated by the immersion method showed a greater
uniformity of coating than by the spraying method (Fig-
ures 2(a) and (b)). This behaviour is related to the ap-
plication process and deposition of the polymer disper-
sion. In the coated particles by immersing was observed
a continuous and smooth layer. In the coating by spray-
ing was observed a rough surface probably due to depo-
sition of polymer in the form of fine particles. Another
factor that may have influenced the morphology of the
particles after the surface was the initial physical state,
before or after drying.
The average particle size of coated systems for im-
mersion method foi de 0.76 to 1.03 mm e de 1.6 mm for
the uncoated systems. These alterations are probably
related to the use of desiccative solvents as the vehicles
Figure 1. Photomicrographs of alginate:
chitosan systems containing triamcinolone
without coating (a) and coated with 1%
Eudragit by the spraying method (b).
of the coating polymers. These solvents may promote
the precocious drying of the systems and thus change
their morphology and size. The systems coated by the
spraying method, 1% Eudragit® and 7.5% HPMCP,
showed average particle sizes of 1.37 and 1.50 mm.
The formulations showed a encapsulation content of
15.47% and 17.97% for particles coated with 7.5%
HPMCP and 1% Eudragit®, respectively. The encapsula-
tion efficiency of the systems was 35.81% ± 9.38%. Be-
ing a slightly soluble drug entrapped in a hydrophilic
system, a greater encapsulation efficiency was expected.
According to Kim et al. [19], the reduction of the matrix
and consequent reduction in the level of encapsulation
could be caused by the electrostatic interaction between
AL and CS, as systems prepared through the AL-Ca
complex, with simultaneous complexation with CS,
show a denser form, hindering drug incorporation.
Drug Release in Gastric and Enteric
Simulated Media
In order to evaluate the behaviour during gastrointes-
tinal transit, the AL:CS systems were evaluated for drug
delivery in different media. Initially the systems were
subjected to simulated gastric medium for 2 hours, fol-
lowed by enteric medium for 4 h and finally colonic me-
dium for 24 h.
N. V. Vier et al. / Natural Science 3 (2011) 955-962
Copyright © 2011 SciRes. OPEN ACCESS
Figure 2. Photomicrographs of alginate:chitosan systems con-
taining coated with HPMCP by immersion (a) and spraying
method (b).
The AL:CS systems were coated with gastro-resistant
polymers (HPMCP and Eudragit®) in order to reduce drug
release in the simulated gastric and enteric environments.
Polymer coatings for colonic-delivery drugs have been
used to protect hydrophilic polymer systems in the higher
GIT, particularly by reducing the swelling ratio in the
enteric medium.
The coated systems showed a lower release rate in the
early hours of testing. In addition to reducing drug re
lease in the stomach, the coatings delayed delivery in the
enteric medium, as the dissolution and/or swelling of the
polymer is necessary for the drug to be delivery.
Figure 3 shows the drug delivery profile of the sys-
tems coated with HPMCP in different concentrations,
prepared by the immersion and spraying coating meth-
ods. It can be seen that drug delivery from the uncoated
system was higher after 6 hours compared to the coated
systems. The systems coated with 7.5% HPMCP pre-
pared by the immersion coating method showed a lower
ratio of drug release, both in the stomach and enteric
Time (min)
0100 200 300 400
Drug released (%)
1% IC
5 % IC
7.5% IC
7.5% SC
AL:CS uncoated
Figure 3. In vitro drug release from the alginate:chitosan sys-
tems coated with HPMCP in different concentrations and by
different coating methods, immersion (IC) and spraying (SC),
in simulated gastric and enteric media.
media, showing total drug retention in the system for the
first 180 minutes. This slower drug release is probably
due to the polymer concentration and the coating method.
By immersion coating method, the increasing the poly-
mer concentration increased the thickness of the coating
and, consequently, the dissolution time increased and,
the rate of drug released was reduced.
When comparing the release rates for the systems
coated with HPMCP and Eudragit®, it was observed that
the particles coated with HPMCP showed greater control
over drug delivery, mainly in gastric simulated environ-
ment. This may be related to gastric protection and
swelling capacity of HPMCP in pharmaceutical applica-
tion of drug controlled release. The polymer swelling in
enteric environment, form a gelled coating which can
control the drug release. Furthermore, the strength of the
HPMCP polymer film coating is determined by its mo-
lecular weight; that is, the higher the molecular weight,
the greater the resistance of the film [20,21] and, cones-
quently, drug controlled release of the these systems is
greater. HPMCP molecular weight values may vary from
78,000 - 132,000 Da [21]. The molecular weight of the
HPMCP polymer used in this study was approximately
84,000 Da. Like HPMC, the HPMCP polymer, unlike
other polymers, has the ability, after the process of sys-
tem hydration, to swell and form a gelatinous layer on
the surface of the particles, which acts as a barrier to
drug release, by controlling water penetration and the
speed of release of the drug. The rate of water in gress
into the matrix system determines how the drug is re-
leased. In very high concentrations, as is the case for
particles coated with 7.5% HPMCP, the linear chains of
the polymer become entangled, resulting in a solid ge-
latinous layer [16].
N. V. Vier et al. / Natural Science 3 (2011) 955-962
Copyright © 2011 SciRes. OPEN ACCESS
In the comparison of the release profiles of the un-
coated system and the systems coated with Eudragit® (by
the immersion and spraying coating methods), the coated
particles present release rate similar to or greater than
the uncoated systems up to 3 hours of proceedings (Fig-
ure 4). After 6 h, the particles coated by spraying and
immersion method released 50% and 74% of drug. For
particles coating with Eudragit, the polymer was dis-
solved in water (pH 6, 8). The need of larger drying time
intervals between the applications of spraying coating
and the influence of the solvent in the flow of polymer
solution can be caused the obtain a coating greater than
10% (w/w), initially expected, and a higher retention of
the drug incorporated in the matrix, differing from the
behaviour observed in matrices coated with PHPMC.
The drug release profile in simulated colonic medium
was carried out in human fecal suspension. According to
Yang [22], there are four methods for in vitro evaluation
of colon-specific delivery systems: conventional simu-
lated enteric environment (0.01 M phosphate buffer), use
of rat fecal content, use of human fecal content and sys-
tems of multi-phase cultures. Fluids with the fecal con-
tent of animals, especially rats, have been used to invest-
tigate polysaccharide fermentation. Animal models, such
as rats, are available, although these models are rela-
tively expensive for research on metabolic processes
mediated by intestinal microorganisms compared to in
vitro models. In addition, the animal’s digestive physic-
ology differs to that of humans [22].
Figure 5 shows the drug release profiles of the sys-
tems in the simulated colonic fluid, after the delivery in
simulated acidic and enteric media. The systems coated
with HPMCP by immersion coating had delivered about
38% of the drug after 24 h in simulated colonic medium.
Time (min)
0100 200 300 400
Drug released %
1% IC
1% SC
AL:CS uncoated
Figure 4. In vitro drug release from the alginate:chitosan sys-
tems coated with Eudragit® by different coating methods, im-
mersion (IC) and spraying (SC), in simulated gastric and en-
teric media.
Time (min)
0200 400 600 80010001800
Drug released (%)
1% Eudragit IC
1% Eudragit SC
Figure 5. In vitro triamcinolone release from the alginate:chi-
tosan systems coated with different polymers in simulated
gastric, enteric e colonic media.
This is probably related to the dissolution of the coating,
swelling and erosion of the systems. The systems coated
with the same polymer by the spraying method had de-
livered approximately 76% of the drug at the end of the
The systems coated with Eudragit® showed a higher
rate of drug release by the end of the assay. Greater drug
release was observed from the systems coated by the
immersion method than by those coated by the spraying
method. Although, only the Eudragit® immersion coat-
ing system released almost all of the drug in the time
period studied, the other systems also showed a constant
decline in delivery, with the HPMCP immersion coating
batch producing the lowest constant and the lowest
amount of drug released after 30 hours of analysis. After
evaluating the speed of triamcinolone release and the
residence time of the formulation in the colon, the for-
mulation coated with HPMCP was found to be the most
promising for the development of colon-specific delivery
Table 1 shows the correlation coefficients of the de-
livery profiles when applied in different mathematical
models in the analysis of the release kinetics. Of the
models studied, the release profiles showed higher cor-
relation coefficients for the Korsmeyer-Peppas model.
This model is used to examine the release of polymeric
dosage forms, when the release mechanism is not well
known or when more than one type of apparently unre-
lated release mechanism may be involved: one due to
drug transport (Fickiano transport) and the other related
to the swelling and matrix relaxation [16].
For the models derived from the Korsmeyer-Peppas
equation, it is the value n that characterizes the drug re-
lease mechanism, depending on the geometric shape of
the particle [16]. Table 2 shows the n values obtained
N. V. Vier et al. / Natural Science 3 (2011) 955-962
Copyright © 2011 SciRes. OPEN ACCESS
Table 1. Correlation coefficients from the application of different mathematical models for the analyses of the kinetics of alginate:
chitosan (AL:CS) systems.
Correlation coefficient (r2)
Korsmeyer-Peppas Baker-Lonsdale Hixon Crowell Higuchi Zero Order First Order
AL:CS 0.9959 0.8002 0.9334 0.8358 0.898 0.9123
1% HPMCP-IC 0.9849 0.8304 0.9634 0.8492 0.8843 0.9540
5% HPMCP-IC 0.9643 0.9988 0.8127 0.9641 0.9622 0.8573
7.5% HPMCP-IC1 0.9905 0.6478 0.8208 0.6502 0.7252 0.8189
7.5% HPMCP-SC2 0.9935 0.9968 0.8233
0.9982 0.9859 0.9189
1% Eudragit-IC1 0.9947 0.8022 0.9779 0.9462 0.9492 0.9691
1% Eudragit-SC2 0.9852 0.9830 0.8693 0.9849 0.9710 0.8906
1Immersion coating method; 2spraying coating method.
Table 2. n values obtained from the application of drug release
profiles to the Korsmeyer-Peppas mathematical model.
n values Transport
1% AL:CS 1.4569 Super Case II
1% HPMCP IC1 1.3886 Super Case II
5% HPMCP IC1 0.5153 Anomalous
7.5% HPMCP IC1 3.3037 Super Case II
7.5% HPMCP SC2 0.5164 Anomalous
1% Eudragit IC1 1.1224 Super Case II
1% Eudragit SC2 0.4848 Classic diffusion
1Immersion coating method; 2Spraying coating method.
for the systems. According to the n values, the TC trans-
port mechanism of the systems can be characterized by
classic diffusion, anomalous transport and super case II
transport, and the mechanism that predominated was
super case II, which is characterized by acceleration in
solvent penetration in the systems. The speed of solvent
diffusion in the matrix is much greater than the swelling,
with this being the determining factor in the drug re-
By analyzing the results of the release profile and ki-
netics, it is possible to better understand the release
mechanism as correlated to the swelling results. The sys-
tems have a greater water uptake (data not presented)
than the swelling ratio, i.e., there is greater absorption
and flow of solvent than the increase of polymeric ma-
trix. Systems had higher proportion of swelling in en-
teric than in acidic media. This behaviour has been ob-
served for systems of chitosan:alginate and chitosan:
pectin [23]. The behaviour of reduced swelling and drug
release in the simulated gastric medium is related to the
ionization of the AL and CS polyelectrolytes. In acidic
pH, CS is protonated with 3
NH amino groups and ani-
onic polyelectrolyte, AL, with non-ionized COOH car-
boxylic groups and tends to precipitate in the medium.
This behaviour can lead to the closure of the structure
and, thus, greater control over drug release in acidic me-
dium. The limitation of AL ionization in acid medium,
which could lead to its insolubility, probably influenced
the release profile behaviour of the coated and uncoated
Coated systems were not eroded in simulate enteric
media promoting the controlled release by mechanisms
of diffusion and swelling. The systems coated by the
HPMCP immersion coating method had a lower swell-
ing ratio compared to the systems coated by the spray
coating method (Table 3), probably due to the greater
uniformity of the coating, so drug diffusion rates in these
systems tends to be lower.
In summary, the different coating methods had an in-
fluence on the uniformity of the coating and the rough-
ness of the particles. Swelling behaviour, water uptake
and drug release were pH dependent. There was a lower
degree of swelling and release in simulated gastric me-
dium than in simulated enteric medium. Drug release
occurred at a slower rate in simulated colonic medium
than in simulated gastric and enteric media. All batches
showed a constant decline in release, with the HPMCP
immersion coating system showing the lowest constant
and the lowest amount of drug released after 30 hours of
analysis. The Korsmeyer-Peppas model was the most
appropriate model for representing the TC delivery pro-
files of the systems, whose transport mechanism can be
characterized by classic diffusion, anomalous transport
N. V. Vier et al. / Natural Science 3 (2011) 955-962
Copyright © 2011 SciRes. OPEN ACCESS
Table 3. Swelling ratio of the alginate:chitosan beads coated
with HPMCP and Eudragit® by immersion and spray coating
method, after 180 min in simulate gastric e enteric media.
Swelling (%)1
Gastric2 Enteric2
1% HPMCP IC3 13.04 (5.95) 145.90 (17.71)
5% HPMCP IC3 8.69 (5.02) 128.12 (10.19)
7.5% HPMCP IC3 –10.38 (1.97) 50.77 (6.43)
7.5% HPMCP SC4 23.33 (2.88) 104.36 (10.80)
1% Eudragit IC3 52.60 (8.93) 163.02 (4.74)
1% Eudragit SC4 25.00 (4.57) 195.02 (5.77)
1Mean ± standard deviation. n = 5; 2Simulate gastric and enteric media; 3IC—
immersion coating method. 4SC—spray coating method.
and super case II transport. From the analysis of all the
results obtained in this study, in can be concluded that
AL:CS multiparticulate systems coated with gastro-re-
sistant polymers represent a promising strategy for thera-
peutic systems requiring colonic drug delivery.
This work was supported by grants from ProPPEC/UNIVALI and
FAPESC, Brazil.
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