DSpace at VNU: Development of a Sustained Release Solid Dispersion Using Swellable Polymer by Melting Method

Pharm Res
DOI 10.1007/s11095-015-1767-2

RESEARCH PAPER

Development of a Sustained Release Solid Dispersion
Using Swellable Polymer by Melting Method
Tuong Ngoc-Gia Nguyen 1 & Phuong Ha-Lien Tran 1,2 & Toi Van Vo 1 & Wei Duan 2 & Thao Truong-Dinh Tran 1,3

Received: 19 February 2015 / Accepted: 4 August 2015
# Springer Science+Business Media New York 2015

ABSTRACT
Purpose This study is to design a sustained release solid dispersion using swellable polymer by melting method.
Methods Polyethylene glycol 6000 (PEG 6000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were used in solid
dispersion for not only enhancing drug dissolution rate but
also sustaining drug release. HPMC 4000 is a common
swellable polymer in matrix sustained release dosage form,
but could not be used in preparation of solid dispersion by
melting method. However, the current study utilized the
swelling capability of HPMC 4000 accompanied by the common carrier PEG 6000 in solid dispersion to accomplish the
goal.
Results While PEG 6000 acted as a releasing stimulant carrier and provided an environment to facilitate the swelling of
HPMC 4000, this swellable polymer could act as a ratecontrolling agent. This greatly assisted the dissolution enhancement by changing the crystalline structure of drug to
more amorphous form and creating a molecular interaction.
Conclusions These results suggested that this useful technique
can be applied in designing a sustained release solid dispersion
with many advantages.
Tuong Ngoc-Gia Nguyen and Phuong Ha-Lien Tran contributed equally to
this work.
* Phuong Ha-Lien Tran

* Thao Truong-Dinh Tran

1

Pharmaceutical Engineering Laboratory, Biomedical Engineering
Department, International University, Vietnam National University, Ho
Chi Minh City, Vietnam

2

School of Medicine, Deakin University, Waurn Ponds, VIC, Australia

3

Institute for Frontier Materials, Deakin University, Waurn Ponds, VIC,
Australia

KEY WORDS poorly water-soluble drug . solid dispersion .
sustained release . swellable polymer

ABBREVIATIONS
FTIR
HPMC 4000
PEG 6000
PM
PXRD
SD
SR

Fourier transform infrared spectroscopy
Hydroxypropyl methylcellulose 4000
Polyethylene glycol 6000
Physical mixture
Powder X-ray diffraction
Solid dispersion
Sustained release

INTRODUCTION
Oral route is preferable in drug administration because of its
convenience, patient compliance and production costs. Poor
bioavailability and low dissolution rate of drug due to poor
absorption, rapid metabolism, and rapid systemic elimination
are challenging issues for scientists. Improving the water solubility of drugs is one of the current strategies in the pharmaceutical industry to overcome those issues (1).
Sustained-release (SR) dosage forms were investigated to
improve patient compliance through reduced multiple dosing
regimens. Moreover, these dosage forms could provide patients with reduced high total dose, a uniform and prolonged
therapeutic effect in systemic circulation, and minimized side
effects (2). In general, the most important issue of SR dosage
forms is the work dealing with poorly water-soluble drugs
because the limited property usually leads to its low bioavailability. The incorporation of poorly water-soluble drugs into
SR carriers using solid dispersion (SD) technique can solve the
above issues by enhancement of dissolution rate, solubility,
oral absorption of water insoluble drugs as well as sustaining
drug release with appropriate polymers (3).


Nguyen et al.

Advantages of polymers such as hydroxypropyl

methycellulose and polyethylene oxide are hydrophilic and
swellable properties which can be utilized in increasing dissolution rate (4–11) and modulating drug release profiles
(12–16). The application of these two polymer properties in
one system could facilitate the design of a dual function drug
delivery system by preparation of SD for dissolution enhancement and compression of matrix tablets for sustained release
(3,17). Regarding conventional SDs, there are still some disadvantages to deal with the preparation methods. With respect to the solvent method, negative effects on the environment, residual of toxic solvent and high cost of production due
to the extra facility for removal of solvents are shortcomings
(9). On the other hand, for melting method, swellable polymers are usually not used as carriers of SD preparation mostly
due to its high viscosity and undetermined melting point. To
overcome those drawbacks, in the current study we would
explore the use of these polymers in SD with melting method
by swelling hydroxypropyl methycellulose in polyethylene glycol 6000 to take a full advantage of for both increasing the
drug solubility and sustained release of the system: (1) as a
carrier in SD for enhanced dissolution of poorly watersoluble drugs and (2) as a polymer for a SR dosage form by
compression of SD powder to form a matrix tablet.

MATERIALS AND METHODS
Materials
Sodium hydroxide (NaOH) was purchased from Guanghua
Sci-Tech Company (China). Hydroxypropyl methyl cellulose
(HPMC 4000) was provided by from Dow Chemical Company
(USA). Polyethylene glycol (PEG 6000) was purchased from
Sino-Japan chemical (Taiwan). Isradipine was purchased from
Shanghai Richem International Company (China). Methanol
(MeOH) and Acetonitrile was purchased from Fisher Scientific
International, Inc (US). Hydrochloric acid (HCl) and Sodium
chloride (NaCl) were purchased from Xilong Chemical Industry Incorporated Company (China). Monopotassium phosphate (KH2PO4) was purchased from Wako Pure Chemical
Industries (Japan). Aerosil® 200 was obtained from Jebsen &
Jessen Chemicals Holding Pte Ltd (Singapore). Mannitol
(Pearlitol®) was purchased from Roquette Pharma Company,

France. Magnesium stearate was purchased from Nitika Pharmaceutical Specialities Pvt. Ltd (India).
Methods
Preparation of Sustained Release Solid Dispersion
PEG 6000 was melted at 160°C until a molten liquid appeared. This temperature was maintained until addition of

Aerosil® 200. HPMC 4000 was added into the beaker of
melted PEG and stirred by a glass agitator for 5 min for the
completed swelling. Then, isradipine was dispersed in the
molten mixture and stirred by a glass agitator for 5 min to
obtain a transparent solution. Next, Aerosil® 200 as a moisture absorbance co-efficient was applied to absorb the molten
mixture. The amount of Aerosil® 200 was selected based on
the wetting state of SD as percentage of carriers changed. The
mixture was then sieved with a 0.5 mm sieve. The obtained
SDs were kept in a dry place, and protected from light until
further use. The detailed formulations were illustrated in
Table I.

Preparation of Sustained Release Solid Dispersion Tablet
The procedure was repeated as the one in section
BPreparation of Sustained Release Solid Dispersion^ with
the ratio 1:4:4 for isradipine, PEG 6000, and HPMC 4000,
respectively. However, a residual amount of HPMC 4000 was
divided into 2 parts. Part 1 was added after isradipine was
dispersed in the molten mixture thoroughly. Part 2 was added
into the blend with Aerosil® 200 to absorb water. The mixture
was sieved with a 0.5 mm sieve. Mannitol was added into the
mixture with an appropriate ratio to perform tablets adequately at a total weight of 150 mg (Table I). Magnesium
stearate as a lubricant was added at the end (1% total mass
of tablet). Single punch-press machine (TDP 1.5, China) with
8 mm-diameter flat punch was used to prepare tablets with a

hardness of around 35–40 N.

Dissolution Studies
Dissolution test machine (DT70 Pharmatest, Germany) was
used for the dissolution studies. These SDs were conducted at
37±0.5°C on an USP specification dissolution test type II
apparatus (Paddle apparatus). The apparatus was set up at
50 rpm of rotation speed. For in vitro dissolution test, buffer
pH 1.2 (900 ml) and buffer pH 6.8 (900 ml) were used as
dissolution media. 1 ml of sample was collected at 10, 20,
30, 60, 90, and 120 min and dissolution media were compensated by adding 1 ml of the corresponding fresh buffer. 100 μl
sample solutions were diluted with 900 μl MeOH for HPLC
test.
To evaluate sustained drug release capability, based on the
previous research submitted by Ching, A.L. et al. (18), each of
750 ml of pH 1.2 was added into dissolution vessel for 2 h and
then 250 ml of 0.2 M sodium phosphate solution (reheated to
37°C) was added to the medium for adjusting to pH 6.8. 2 M
HCl solution (or 2 M NaOH solution) was used for minor
adjustment of the pH of dissolution media. 1 ml of sample
was collected at 1, 2, 6, 10, 14, 18, and 24 h.


Swellable polymer by melting method
Table I

Formulation Compositions of SD Powder (from F1 to F5) and Sustained Release Solid Dispersion Tablet (F6, F7, F8)

Formulation

IS (mg)

PEG 6000 (mg)

HPMC 4000 (mg)

Aerosil (mg)

Mannitol (mg)

Magnesium stearate (mg)

Ratio

Total (mg)

Comments

F1

5

10

–

10

–

–

1:2

25

SD granule

F2

5

20

–

15

–

–

1:4

40

SD granule

F3
F4

5
5

10
20

5
10

10
15

–
–

–
–

1:2:1
1:4:2

30
50

SD granule
SD granule

F5
F6

5
5

20
20

20
20

15
15

–
88.5

–
1.5

1:4:4
1:4:4

60
150

SD granule
Tablet

F7

5

20

30

15

78.5

1.5

1:4:6

150

Tablet

F8

5

20

40

15

68.5

1.5

1:4:8

150

Tablet

HPLC Analysis
The quantification of isradipine was performed using an Ultimate 3000 HPLC Thermoscientific Inc., USA. The mobile
phase consisted of methanol: water: acetonitrile mixture ratio
was 7:3:5 with a flow rate of 1 ml/min and the running time
was around 5 min. The UV/VIS detector was set to a wavelength of 325 nm. 20 μL of sample was injected to the HPLC
system.
Characterization by Powder X-ray Diffraction (PXRD)
In this study, pure isradipine, PEG 6000, HPMC 4000,
physical mixture (PM), and SD samples were analyzed by
PXRD. Diffraction patterns were recorded using a Powder
X-ray diffractometer (BRUKER’ D8 Advance Series
PXRD, Germany) using Ni-filtered, CuKα (λ=1.54060 Å)
radiation at 40 kV and 40 mA. Samples were held on quartz
frame. Drug sample was scanned in a 2θ range from 5 to 50°
with a receiving slit 0.1 mm.
Characterization by Fourier Transform Infrared Spectroscopy
(FTIR)
The physicochemical properties of pure isradipine, PEG
6000, HPMC 4000, PM, and SD samples were characterized
by using Spectrotometer (Bruker’s Vertex 79 series FT-IR,
Germany). KBr were prepared by mixing 1 mg of samples
with 200 mg KBr. The wavelength was from 500 to

4000 cm−1 and the resolution was 2 cm−1.

RESULTS AND DISCUSSION
Dissolution Studies of SDs
The aim of this study was to investigate a new method not only
to increase dissolution rate but also to sustain drug release by
coordinating a poorly water-soluble drug with a swellable
polymer in PEG 6000-based SD. When pure isradipine was

sprinkled in water, the powder floated on the surface of the
medium and prevented surface powder from contacting with
the medium, resulting in poor solubility and low dissolution
rate. As expected, the presence of PEG 6000 increased drug
dissolution directly proportional to PEG 6000 concentration
in the formulation. The interfacial tension between hydrophobic drug and dissolution medium was reduced by PEG 6000
due to hydrophilic property of the polymer, leading to more
area surface and greater wetting (19). Thus, the higher PEG
6000 proportion, the higher drug dissolution rate. Figure 1
illustrates dissolution profiles of isradipine from SDs at different ratios without HPMC 4000 as a function of time in gastric
fluid (pH 1.2) and intestinal fluid (pH 6.8). SDs of the formulations at 1:2 and 1:4 ratio got the moderate percentage drug
release after 2 h in both medium. Specifically, at pH 1.2 drug
released from F1 and F2 was reached at 42.7 and 53.8%,
respectively; whereas, at pH 6.8 it increased to 44.8 and
60.5% for F1 and F2, respectively. Generally, there is an insignificant difference between the drug releases in both dissolution media regardless of isradipine pKa due to the formation
of SDs whose dissolution rates mainly depend on drug crystal
changes or drug-polymer interactions.
figure 2 shows the effect of HPMC 4000 at different ratios
on dissolution profiles of isradipine to determine a suitable
HPMC proportion for a sustained release system. The presence of adequate HPMC 4000 in the formulation could increase dissolution rate of SD up to two folds compared to the
formulation without HPMC 4000. Sufficient HPMC 4000

proportion introduced to the formulation could be observed
through a yellow colored transparent blend. The release rate
of SD at 1:2:1 ratio (F3) was increased to 80.8 and 81.7% at
pH 1.2 and pH 6.8, respectively. This result was impressive as
compared to the corresponding SD without HPMC 4000.
Similarly, while SD at 1:4 ratio without HPMC 4000 (F2)
reached the highest percentage drug release at 53.8 and
60.5% at pH 1.2 and pH 6.8, respectively, dissolution rate
of the formulation at 1:4:2 ratio (F4) in the presence of HPMC
4000, increased strongly to 87.5 and 85.1% at pH 1.2 and
pH 6.8, respectively. Significantly, drug released from the formulation at 1:4:4 ratio (F5) was achieved at approximately


100

120

80

100

% Drug release

% Drug release

Nguyen et al.

60

40

80
60
40

1:2
1:4

20

(a)

20

0
0

20

40

60

80

100

1:2:1
1:4:2
1:4:4

(a)

0

120

0

20

40

Time (min)
100

80

100

120

120

80

100

% Drug release

% Drug release

60

Time (min)

60

40
1:2
1:4

20

(b)

60
1:2:1
1:4:2
1:4:4

40

(b)

0
0

80

20

40

60

80

100

120

Time (min)

20
0

20

40

60

80

100

120

Time (min)

Fig. 1 Dissolution profiles of isradipine from SDs of F1 and F2, at different
ratio without HPMC 4000, as a function of time in gastric fluid (pH 1.2) (a) and
intestinal fluid (pH 6.8) (b).

Fig. 2 Dissolution profiles of isradipine from SDs of F3, F4 and F5, based on
different ratios with HPMC 4000, as a function of time in in gastric fluid
(pH 1.2) (a) and intestinal fluid (pH 6.8) (b).

100% in the first 10 min. Drug dissolution rate was increased
with the increase of HPMC 4000 concentration. This tendency may occur due to the change in drug crystals or molecular
interactions, which will be discussed in the sections below. For
these reasons, F5 with the ratio 1:4:4 was chosen to be the best
fit model in SD formulations.

increasing HPMC content as polymer chain uncoil slowed
(21). Chain entanglement increased the tortuousness of matrix
tablet with the increasing concentration of higher levels of
HPMC (22,23). Additionally, low porosity produced by high
hardness also controlled dissolution rate because it inhibited
liquid across the surface of matrix tablet system (24).
The sustained release profile was achieved at the 1:4:8 ratio
while a little rapid release was observed at the ratios of 1:4:4
and 1:4:6 in tablet dosage forms. Specifically, there was a
strong burst release after 2 h from F6 tablets, increasing from
59.4 to 86.2% in the range of 2–6 h (Fig. 3). However, a
significant sustained release was observed as compared to
the SD powder (F5) due to the presence of matrix tablets
during the dissolution test. The drug release was then increased slowly following a constant rate during the next
18 h. Meanwhile, dissolution rate of SD from F7 tablets

(1:4:6 ratio for IS: PEG: HPMC) exploded from 6 to 10 h,
resulting in a twofold growth of drug release from 44.3 to
88.3% which then became stable. Therefore, the increase in
HPMC 4000 concentration could improve drug dissolution as
well as control the percentage of drug release. However, the

Dissolution Studies of Sustained Drug Delivery System
For a sustained release HPMC matrix tablet, the polymer has
to go through hydration process to form an outer gel layer on
the tablet surface. This process occurs gradually when tablets
contact with the medium, leading to HPMC chain relaxation,
followed by the occurrence of erosion of the matrix. Matrix
swelling, erosion and diffusion of drug are attributed to factors
which controlled the drug release rate and mechanism (20).
The preliminary studies obviously identified the relationship
between HPMC 4000 ratio and the release behavior of SDs
from the hydrophilic matrix system. The percentage of
HPMC 4000 substantially affected the dissolution rate,
resulting in the reduction of dissolution rate with the


Swellable polymer by melting method
120

Physicochemical Characterization

% Drug release

100
80

60
40

1:4:4
1:4:6
1:4:8

20
0
0

5

10

15

20

25

Time (hours)
Fig. 3 Dissolution profiles of isradipine from SR-SDs of F6, F7, and F8 in
24 h.

premature burst release may lead to a fast decrease of
drug concentration in effective life time. Therefore, the
concentration of HPMC 4000 would be increased to
avoid the risk of burst release. F8 tablets (1:4:8 ratio)
showed their ability in sustaining drug delivery system

through the capability of retaining the shape of matrix
tablets up to 10 h while this period of the same performance in other SDs was 6 h. Furthermore, drug was
gradually released from F8 during 24 h. Gel layer formation around the matrix tablet can control drug release rate regardless of the effect of drug solubility.
Higher HPMC 4000 concentration in formulation
formed gel layer quicker and stronger, leading to increased resistance of drug to diffusion and erosion
(23). Furthermore, the barrier of HPMC 4000 is less
efficient in diminishing drug release rate. On the other
hand, the translocation of water insoluble drug particles
through the gel layer can disrupt the gel layer structure
(25), resulting in a burst release in dissolution. The formulation at 1:4:8 ratio (F8) provided sufficient amount
of HPMC 4000 to develop a rapid formed and strong
gel layer around the matrix tablet to sustain drug release and prevent burst release during dissolution or
hydration.
The empirical observations and experimental results indicated that HPMC was a useful swellable polymer with high
applicability for both increased dissolution rate and sustained
drug delivery system. Melting method has some advantages
including short time process, solvent-free, lower cost, and prevention of toxicity in the environment. Therefore, the preparation in the current study is very convenient for further research and manufacturing. Besides, time – controlled release
can be regulated by applying appropriate polymer carriers
concentration to optimize therapeutically efficiency with better patient compliance.

figure 4a displays X-ray diffractograms of pure isradipine,
PEG 6000, PM, SDs at ratio of 1:2 (F1) and 1:4 (F2) to investigate the effect of different ratio between drug and PEG 6000
without HPMC 4000 on the physical state of SDs. The
diffractogram of isradipine showed numerous peaks, indicating its high crystallinity in nature. The change from crystalline
state to amorphous state was identified by the disappearance
of instinctive peaks or great diminution in number of characteristic peaks. In case of F1, although most of peaks disappeared, peaks at 9.4, 9.8, 11.4, 11.8, 12.2, 13.9, 16.9, 17.6,
19.1, 20.5, 23.3, 25.5, 26.7, and 28.4 2θ still remained. Therefore, SD was partially transformed into its amorphous form.
In SD at 1:4 ratio (F2), the absence of peak at 9.4, 9.8, 11.4,
11.8, 12.2 2θ compared to F1 demonstrated that the amorphous state of SD was improved with the increase of hydrophilic carrier PEG 6000 concentration. A new peak was noted
at the position of 10.6 2θ. The result suggested an interaction

between isradipine and PEG 6000.
The effect of HPMC 4000 concentration on the physical
state of SDs was indicated in Fig. 4b. HPMC 4000 altered
structure of SD formulations into more amorphous form. SD
with 1:2:1 ratio (F3) still kept some main peaks from pure
isradipine such as 11.8, 13.9, 16.9, 17.6, 19.1, 20.5, 22.2,
and 23.3 2θ. However, some peaks at 9.4, 9.8, 11.4, 11.8,
and 12.2 2θ were disappeared, leading to more amorphous
form in SD formulation. Some peaks at 9.4, 9.8, 25.5, 26.7,
and 28.4 were reduced in intensity compared to F1 (1:2 ratio),
suggesting that HPMC 4000 helped transformation easier
from crystalline to amorphous form. In case of F4 (1:4:2 ratio),
there was the disappearance of some peaks at 11.8, 13.9, 17.6,
20.5 2θ compared to F3 (1:2:1 ratio). Meanwhile, F5 (1:4:4
ratio) just showed three main peaks of pure isradipine: 6.9,
19.1, 23.3 2θ. While PEG 6000 provided one characteristic
peak at 21.3 2θ in both F3 (1:2:1 ratio) and F4 (1:4:2 ratio), this
peak didn’t appear in F5, F7, F8 (1:4:4, 1:4:6, 1:4:8 ratio). It
was suggested that the amount of HPMC 4000 in F5 was
sufficient to change SD to its amorphous form. The appearance of the new peak at 10.6 2θ in both three SDs with a
gradually decrease in intensity confirmed a reaction between
isradipine and PEG 6000. The descending in intensity of this
peak might be caused by the increased HPMC 4000 concentration in the formulation, which facilitated the dispersion of
drug in carrier. The excessive amount of HPMC 4000
changed the structural behavior of the drug into amorphous
state, resulting in the increasing of dissolution rate.
Research submitted by Ramasahayam at el. showed the
isradipine spectra with well-defined functional groups (26). A
sharp peak at 3345 cm−1 was aliphatic amine stretching (N-H
group). Three characteristic bands of carboxylic acid groups

was presented at 1700 cm1 (C=O carboxylic acid stretching),
1366, 1309 cm−1 (C – O carboxylic acid stretching), and


Nguyen et al.

(a)

(a)
PEG 6000

Pure Isradipine

PEG 6000

PM

Pure Isradipine
1:2

PM

1:2

1:4

1:4

10

20

30

40

50

Position (2-Theta)
4000

(b)

3000

2000

1000

Wavelenth (cm-1)

(b)
1:2

1:2
1:4

1:2:1

1:4

1:2:1

1:4:2

1:4:4
1:4:6

1:4:2
1:4:4

1:4:8
1:4:6

10

20

30

40

50

1:4:8

Fig. 4 (a) PXRD patterns of isradipine, PEG 6000, PM and SDs of F1 and F2
in different ratios. (b) PXRD patterns of isradipine, PEG 6000, HPMC 4000,
PM and SDs of F3, F4 and F5 in different ratios.

1001 cm−1 (O – H carboxylic acid out of plane bending). The
alkane group assigned peaks at 2943 cm−1 as C – H alkane
stretching and 1488 cm−1 as CH3 alkane in the plane bending.
Moreover, peak at 1488 cm−1 might identify C=C aromatic

4000

3000

2000

Wavelenth

(cm-1)

1000


Swellable polymer by melting method

ƒFig. 5

(a) FTIR spectra of isradipine, PEG 6000, PM and SDs of F1 and F2 in
different ratios. (b) FTIR spectra of isradipine, PEG 6000, HPMC 4000, PM
and SDs of F3, F4, and F5 in different ratios.

ring stretching (26,27). C-N amine stretching was located at
1219, 1120, 1108, 1018 cm−1; whereas, C-H aromatic out of
plane bending was appeared at 868, 757, 742, 620 cm−1.
Figure 5a shows the FTIR spectrum of pure isradipine, PEG

6000, and SDs of 1:2 ratio (F1) and 1:4 ratio (F2) without the
presence of HPMC 4000. The spectrum of F1 showed that the
entirely main function groups of pure isradipine were
remained. In F2 (1:4 ratio), there was two small peaks at
3345 and 2885 cm−1, indicating the existence of isradipine
and PEG 6000 in formulation. Different from F1, the peak
at 1704 cm−1 of F2 was divided into two small peaks, resulting
the formation of hydrogen bonding between carbonyl C=O
group of isradipine and O-H group of PEG 6000. There was
only one carbonyl peak shifted downwards, inferring that only
one of C=O groups of isradipine was hydrogen bonded;
whereas, the other was non-hydrogen bond or very weakly
hydrogen bond (28,29). It could explain why F2 was dissolved
better than F1. FTIR spectra in Fig. 5b illustrated the effect of
presence of HPMC 4000 at different ratios on dissolution
profile of isradipine. In case of F3 (1:2:1 ratio), some characteristic peaks of pure isradipine were still maintained. Similar
to F2, the two carbonyl groups of isradipine in F3 were observed, indicating the intramolecular hydrogen bonding in the
structure. Thus, F3 with the presence of HPMC 4000 in formulation gave better drug dissolution. SDs at ratio 1:4:2 (F4)
and 1:4:4, 1:4:6, 1:4:8 (F5, F7, F8) showed that the only one
carbonyl group was observed at these SDs at around
1696 cm−1. This peak was overlapped by two carbonyl
groups, indicating that no hydrogen bonding occurred. However, there was no amine group (N-H) at 3345 cm−1, attributing to the intramolecular hydrogen bonding with anion between aliphatic secondary amine NH of isradipine and OH
group of PEG 6000 (28,29). This might be explained that NH stretching frequency was quite high (3345 cm−1) as compared to other compounds, leading to the fact that the hydrogen bonding was stronger than other counterparts (29). The
result also explained why the more HPMC 4000 the more
increased drug dissolution. Furthermore, the IR spectra of
F4 and F5 were similar, suggesting that the increase of
HPMC 4000 concentration did not change the chemical
behaviors of relative formulations. Nevertheless, F5 had significantly higher drug dissolution might be due to the more
amorphous state.

CONCLUSION
This study investigated a SR system based on the combination
of a hydrophilic carrier and a swellable polymer in SD melting

method. The presence of the swellable polymer not only increased dissolution rate but also sustained drug release from
the matrix tablet. The interesting point herein is that although
melting method is a promising method in solid dispersion
preparation with some advantages such as short time process,
solvent-free, lower-cost, and prevention of toxicity, etc., a
swellable polymer was usually not applied as hydrophilic carrier even. This study indicated that the sustained release function could be designed in a SD formulation in addition to the
role of enhancing drug dissolution of poorly water-soluble
drugs by a selection of an appropriate polymer type and concentration. Hence, the dual function SD could bring patients
optimized therapeutic efficiency and compliance and pharmaceutical industry a potential product with convenient manufacture. FTIR and PXRD results elucidated the ability of SD
system in enhanced dissolution rate and sustained drug release
by structural behaviors changes from crystalline to amorphous
form and intermolecular hydrogen bond.

ACKNOWLEDGMENTS AND DISCLOSURES
This research is supported by Vietnam National University –
Ho Chi Minh City. We also thank to International University
for their continued, generous and invaluable support to our
studies as well as greatly boost the efficiency of our research
activities

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