107

TP CH KHOA HC V CNG NGH Tp 44, s 3, 2006 Tr. 107-111

SYNTHESIS AND SWELLING BEHAVIORS OF THE
(N-ISOPROPYLACRYLAMIDE-co- MALEIC ACID-co-
2-HYDROXYETHYLMETHACRYLATE) COPOLYMERIC
HYDROGELS
HOANG DUONG THANH, TRAN THI NHU MAI, BUI THAI THANH THU,
NGUYEN VAN KHOI, TRAN VU THANG
I. INTRODUCTION
Hydrogels synthesized from water-soluble monomers, which have three-dimensional
networks that swell but undissolve in water. Some of hydrogels undergo a great volume change
in response to a change in surrounding conditions, such as pH, temperature, photoirradiation,
and electric field, etc, [1 - 3] so they called sensitive hydrogels. Poly (N-isopropylacrylamide)
poly (NIPA) is one of the best thermotropic polymers and exhibits a lower critical solution
temperature (LCST) [4 - 7]. In this article, pH thermosensitive hydrogels were synthesized by
redox copolymerization of NIPA, maleic acid (MA), 2-hydroxyethyl methacrylate (HEMA) and
N, N- methylene-bis-acrylamide (MBA) and applied in release of caffeine.
II. EXPERIMENTAL
1. Materials
N-isopropylacrylamide (NIPA) was supplied by Wako - Japan, 2-hydroxyethylmethacrylate
(HEMA), N, N- methylen-bis-acrylamide (MBA), Ammonium persulfate (APS), and acid (L)
ascorbic were supplied by Merck - Germany, Maleic acid (MA) purchased from Kanto - Japan.
Caffeine as a model drug was used as received from Fluka - Japan.
2. Preparation of hydrogels
HEMA, NIPAM and MA monomer in various ratios were dissolved in distilled water to
obtain 1 M of total concentration. The cross-linking agent MBA was added to reaction solution
in desired concentration (3% total mole concentration of monomer), the mixture was
continuously agitated by magnetic stirrer. After that 1.5 % mole ratio base on total monomer
content of APS and (L) ascorbic acid, in solution 10%, as redox initiators were added to this
solution, and the mixture was immediately poured into teflon round mold with the radius is 2
cm, and 2 mm of thickness. The sample is maintained at 35
o
C in 6 hours to ensure completely
crosslinking. The products are immerged in distilled water for 4 days to distract all of remained
monomer and other impurities. The final product is dried into vacuum oven at 50
o
C to
unchanged weight.
3. Equilibrium swelling ratio [3]
The preweighed (Wd) dried gels were immersed in an excess of distilled water at different
temperatures until swelling equilibrium was attained. The weight of wet sample (Ww) was
determined after removing the surface water by blotting paper. Swelling ratio (SR) was
calculated from the following equation:

108
SR

=
Wd

Wd - Ww
(SR: Swelling ratio).
4. Measurement of drug released
Dissolve 300 mg caffeine in 100 ml of distilled water. The 20 ml of caffeine solution was
taken into a cup. The dried hydrogel species placed in that solution for 2 days at room
temperature to get equilibrium swollen. The solution on the surface of samples was removed by
blotting paper before measuring. Then the caffeine-adsorbed hydrogels were put in a cup of 20
ml of distilled water in every 30 minutes for caffeine releasing determination. This step was
repeated in four hours. The releasing caffeine solutions were analyzed at 272 nm by colorimeter
HACH_RD 9000.
III. RESULTS AND DISCUSSION
Thermosensitive hydrogels were prepared by various mole of NIPA/HEMA ratio in the
presence of 3% MBA as cross-linker. To study the effect of temperature on the equilibrium
swelling ratio, the samples of hydrogel were swollen in distilled water at temperature range from
25 - 50
o
C, the results were shown in Fig. 1.
0
2
4
6
8
10
12
25 30 35 40 45 50
Temprature (oC)
E
q
u
i
l
i
b
r
i
u
m

s
w
e
l
l
i
n
g

r
a
t
i
o
(
g
/
g
)
0%NIPA
25%NIPA
50%NIPA
75%NIPA
100%NIPA

Figure 1. Swelling equilibrium as a function of temperature
The hydrogel without NIPA almost unchanged in equilibrium swelling on the temperature,
that mean it was insensitive with temperature. In contrast, the samples in the presence of NIPA
has change equilibrium on temperature and the collapsing point the more clearly realized by
increasing NIPA content. This is due to NIPA has negative thermal sensitivity. Hydrogel with
NIPA/HEMA mole ratio 75 : 25 has LCST at 36.75
o
C around body temperature, is used for
further studies.
To prepare pH and thermo - sensitive hydrogels, copolimerization was caried out at mole
ratio of 75/25 NIPA and HEMA in the presence of MA amount range from 1 to 4 percent. Effect
of pH on the swelling equilibrium ratio of hydrogel with various MA contents was illustrated in
Fig. 2.

109
0
2
4
6
8
10
12
0 2 4 6 8 10 12 14
pH
E
q
u
i
l
i
b
r
i
u
m

s
w
e
l
l
i
n
g

r
a
t
i
o

(
g
r
/
g
r
)
0% MA
1% MA
2% MA
3% MA
4% MA

Figure 2. Effects of MA content on equilibrium content
The result shown that, swelling equilibrium ratio increased by enhancing the MA content.
This is due to by increasing the MA content in hydrogel, the carboxylate ion created from acid
functional group solvation made the gel more affinity with the solvent. And than the swelling
ratio is increased.
At alkali pH, strongly solvation happened and higher affinity with solvents leading to
sudden growth up of swelling ratio.
The data in Fig. 3 shown that, the LCST of hydrogel increasing slightly with rising MA
content of hydrogel in studying range 1-4 percent.
36
36.5
37
37.5
38
0 1 2 3 4
% MA
L
C
S
T

(

C


Figure 3. LCST of hydrogel as a funtion of maleic acid's content
For drug releasing study, hydrogel with 2% MA content, which has LCST is approximate
37
o
C equivalent to human body temperature, was chosen for further investigates.

110
The Fig. 4 shown the kinetic of caffeine releasing process of hydrogel with NIPA/HEMA
75 : 25 mole ratio and 2% mole MA.
0
20
40
60
80
0 1 2 3 4 5
time(h)
R
e
l
e
a
s
e
d

(
%
)

Figure 4. Caffeine released as a function of time
In Fig. 4, the amount of released caffeine increases with the time. However, there are a
number of caffeine molecular were kept in hydrogel network.
IV. CONCLUSION
The affect of NIPA/HEMA ratio to hydrogels LCST was investigated. The results showed
that 75: 25 of NIPA/HEMA ratio, at which hydrogels LCST is approximate 36.75
o
C, is suitable
for further studying of copolymerization and drug releasing. Besides, hydrogel 2% mole MA
was preferred to improve pH sensitive. Finally, hydrogel with NIPA/HEMA 75 : 25 mole ratio
and 2% mole MA exhibits a release of caffeine.
REFERENCE
1. J. Kopecek, J. Vacik, and D. Lim - J. Polym. Sci. A-1 (9) (1971) 2801.
2. J. Grigon, A. M. Scallan - J. Appl Polym Sci. 25 (1980) 2829.
3. T. G. Park, A. S. Hoffmal - J. Appl Polym Sci. 46 (1992) 659.
4. Y. H. Bae, T. Okano, and S. W. Kim - J. Polym Sci. B 28 (1990) 923.
5. Wen- Fu Lee, Yu- Lin Huang - J. Appl Polym Sci. 77 (2000) 1769.
6. K. Otaka, H. Inomata, M. Konno, and S. Saito - Macromolecules 23 (1992) 283.
7. Y. Hirokawa, T. Tanaka - J. Chem. Phys. 81 (1984) 6379.
SUMMARY
A series of pH Thermorsensitive hydrogels that exhibited volume phase transition, was
synthesized by various molar ratios of N isopropylacrylamide (NIPAM), maleic acid (MA)
and 2- Hydroxyethyl methacrylate (HEMA). The influence of some factors such as temperature
and pH value on the swelling behavior of these copolymeric gels was investigated. Hydrogels
were used in release of caffeine with changes in time.


111
TNG HP V NGHIN CU TNH CHT TRNG CA HYDROGEL
COPOLYME (N-ISOPROPYLACRYLAMIT-co-MALEIC AXIT-co-
2-HYDROXYETYLMETACRYLAT)
Cc hydrogel nhy nhit v pH c th tch chuyn pha c tng hp vi cc t l mol
N-isopropylacrylamit (NIPAM), axit maleic (MA) v 2-hydroxyetyl metacrylat (HEMA) khc
nhau. nh hng ca mt s yu t nh gi tr pH v nhit ti tnh cht trng ca cc gel
copolyme ny c nghin cu. Cc hydrogel c s dng nghin cu qu trnh nh
caffein theo thi gian.

a ch: Nhn bi ngy 2 thng 3 nm 2005
Hoang Duong Thanh. Ministry of Industry.
Tran Thi Nhu Mai, Bui Thai Thanh Thu,
Faculty of Chemistry, University of Natural Sciences, Hanoi National University.
Nguyen Van Khoi, Tran Vu Thang,
Institute of Chemistry, Vietnamese Academy of Science and Technology.