Preparation and Characterization of Glucosamine Nanoparticle
by Ionic Gelation Method Using Chitosan and Alginate
Yuli Agung Prasetyo, Marline Abdassah, Taofik Rusdiana*
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas
Padjadjaran, Bandung, Indonesia, 45363
Received : 24 Sept 2018/Revised : 6 Nov 2018/Accepted : 9 Des 2018/Published 21 Jan 2019
ABSTRACT
Osteoarthritis is a chronic degenerative disease of the joints that usually treated by NSAID drugs in the
long term leading to cardiovascular and gastrointestinal disorders. Glucosamine is a precursor in the
formation of progression of joint which have not a significantly side effect. The problem in glucosamine
administration occured when it is administered through the oral route resulting in first pass metabolism,
while when it is administered via intavena route resulting in insulin resistance. Those problems can be
solved by developing glucosamine into nanoglucosamine in order to increase the enzymatic stability
which will protect the active ingredient from diminishing by the first pass effect hence the dose can be
reduced, consequenlty it will reduce the insulin resistance, and increase the permeation. In this study,
the nanoparticles of glucosamine with chitosan polymer and crosslinker alginate was prepared by the
ionic gelation method with the principle of continued cross forming polyelectrolyte complexes. This
study started from preformulation such as solubility and identify study by FTIR, then the formulations
of chitosan: glucosamine: alginate = 5:1:1 (volume ratio) with the variation of concentration in the FI
(chitosan: glucosamine: alginate = 0.08 %: 0.1%: 0.08%) and FII (chitosan: glucosamine: alginate =
0.1%: 0.1%: 0.08%). Results of nanoparticle characterization by particle size analyzer in the FI showed
the better formula indicating a foggy coloid, no precipitation, the pH was 2.90±0.05, and the percent
transmittance was 99.35%. The distribution of particle size, polydispersit y index, and zeta potential
for the formula I were 76.0 ± 21.8 nm; 0.300; and -0.30 mV, respectively. It could be concluded that the
nanoparticle system of glucosamine can be better prepared from the 0.08% of chitosan, 0.1% of
glucosamine and 0.08% of alginate.
Keywords: alginate, chitosan, ionic gelation method, glucosamine nanoparticle
1. Introduction
Glucosamine (2-amino-2-deoxi-β-d-
glucopyranose) is a substance found in the matrix
of cartilage and joint fluid of the human joint.
Glucosamine is present in almost all soft tissues in
the human body with the highest concentration in
cartilage (1). Based on case reports, the efficacy of
glucosamine is very high, able to control the
progression of changes in the anatomical structure
of the joints in osteoarthritis (2). The use of oral
glucosamine causes the bioavailability of
glucosamine to be low by 44% although its
concentration in blood is found to be very high.
This is because the first pass metabolism of
glucosamine in the liver. In the form of intravenous
infusion, glucosamine is found in high doses in the
body and may increase the risk of insulin resistance
due to its metabolism in the glycolysis cycle (3).
The presence of topical preparations to be a
solution in overcoming these problems. However,
topical glucosamine preparations circulating in the
market have not had the desired efficacy.
Therefore, it is recommended to reduce the size of
glucosamine to nanoglucosamine. Nanoparticles
can increase glucosamine permeation, so the
efficacy of glucosamine increases (4,5).
Nanoparticles can be made by ionic gelation
method. The ionic gelation is a method of making
by crosslinking which strengthens the mechanical
strength of particles formed between polymers and
crosslinkers (6). Chitosan is a polymer that has
been developed because it is biocompatible,
biodegradable, non-toxic (7), and is a potential
*Corresponding author, https://doi.org/10.24198/idjp.v1i1.13924
e-mail : t.rusdiana@unpad.ac.id (T. Rusdiana) 2019 Prasetyo et al
Vol 1, Issue 1, 2019 (1-10)
http://journal.unpad.ac.id/idjp
Y.A. Prasetyo et al / Indo J Pharm 1 (2019) 1-10
2
biomaterial as a carrier in drug delivery systems
(8). Crosslinker polyanion alginate improves the
basic structure of chitosan to form a polyelectrolyte
complex (9) and prevents the destruction of the
active compounds in chitosan nanoparticles (10).
From this background, we conducted a study on the
preparation of glucosamine nanoparticles with
chitosan polymers and alginate crosslinkers using
ionic gelation methods including the formulation
stages and characterization of glucosamine
nanoparticles.
2. Method
2.1. Preformulation
2.1.1. Fourier Transform Infrared
Glucosamine, chitosan, and alginate analyzes
were each performed using infrared spectroscopy.
For infrared spectroscopy, 1 mg of sample was
mixed with ± 200 mg KBr, and then made pellet
(disc). Measurements using infrared spectroscopy
at range of 4600-400 cm
-1
(11).
2.1.2. Solubility
Glucosamine has a 1 : 10 solubility in water with
a pH between 3 to 5 (12). Chitosan with free amino
form is not always soluble in water and practically
insoluble in 95% ethanol, other organic solvents
and neutral or base solutions at pH greater than 6.5,
thus requiring acid to dissolve them. Chitosan is
soluble in concentrated organic acids as well as
dilute, one of which is dilute acetic acid (13).
Sodium alginate is water-soluble, insoluble in
alcohol, and a hydroalkoloid solution with an
alcohol content of more than 30%, and is insoluble
in chloroform, ether, and acid with a pH of less than
3 (14).
2.2. Formulation
2.2.1. Preparation of acetic acid solvent 1.5% v/v
1.5% v / v acetic acid solvent was prepared by
dissolving 15.3 mL of glacial acetic acid 98% with
distilled distillate to 1000 mL.
2.2.2. Preparation of glucosamine, chitosan and
alginate
Glucosamine, chitosan and alginate solutions
were prepared according to the predetermined
concentration of chitosan in 1.5% v / v acetic acid
(0.08%, 0.09%, 0.10%, and 0.20% w / v) ,
Glucosamine in aqua distillata (0.10% w / v), and
alginate in aquadistillata (0.08%, 0.09%, and
0.10%). Furthermore, sonication for 25 minutes.
2.2.3. Optimization of glucosamine nanoparticles
formula
Optimization was performed by determining the
ratio of the volume of the concentration ratio of the
materials used in the formulation of chitosan
(0.08%, 0.09%, 0.10%, and 0.20% w / v),
glucosamine (0.10% w/v), and alginate (0.08%,
0.09%, and 0.10%). Comparison of volumes used
are chitosan: glucosamine: alginate (5 : 1 : 1 and 10
: 1 : 1). Glucosamine solution is dropped into
chitosan solution by using syringe and
homogenized with magnetic stirrer at 1500 rpm for
60 min at room temperature. Alginate solution is
slowly dropped by using a syringe homogenized
with a magnetic stirrer at a rate of 1500 rpm for 30
minutes at room temperature. The resulting
nanoparticle dispersion system then measured
percent (%) transmittant using UV-Vis
spectrophotometry as initial characterization.
2.2.4. Formulation of glucosamine nanoparticle
The best optimization results are then
formulated. Glucosamine solution is dropped into
chitosan solution by using syringe and
homogenized with magnetic stirrer at 1500 rpm for
60 min at room temperature. Alginate solution is
slowly dropped by using a syringe homogenized
with a magnetic stirrer at a rate of 1500 rpm for 30
minutes at room temperature. The resulting
nanoparticle dispersion system then measured
percent (%) transmittant using UV-Vis
spectrophotometry as initial characterization.
Y.A. Prasetyo et al / Indo J Pharm 1 (2019) 1-10
3
2.3. Characterization
2.3.1. Organoleptic
Physical observations made on the formulation of
glucosamine nanoparticles with chitosan polymers
and alginate crosslinkers include three things:
color, clarity (% transmittance), and pH.
Measurement of transmittance percent by
measuring 3 mL sample using UV-Vis
spectrophotometer with wavelength 650 nm (15).
a. Size and size distribution of particle
Size and particle size distribution were performed
with a 100 μL nanoparticle suspension dispersed at
50 mL aquadest and measured immediately with
the Particle Size Analyzer (16).
2.3.2. Zeta potential
The zeta potential is used to characterize the
surface charge nature of the particles (17). The 100
μL nanoparticle suspension was dispersed at 50 mL
aquadest and measured immediately with the
Zetasizer tool (16).
2.3.3. Polydispersity index
The 100 μL nanoparticle suspension was
dispersed at 50 mL aquadest and measured
immediately with the Particle Size Analyzer (16).
2.3.4. Determination of nanoparticle functional
groups with FTIR
The formed nanoparticles are characterized by
their infrared spectra using the FTIR instrument.
3. Result
3.1. Preformulation
Identification of glucosamine standard and
sample and also chitosan standard and sample used
in this study performed by using the Fourier
Transform Infrared Spectroscopy (FTIR), the
results were shown in the fig. 1 and 2. The FTIR
spectrum of alginate as a cross-linker for nano
material have also been identified and shown in the
figure 3.
3.2. Solubility
The solubility of glucosamine, chitosan and
alginat were performed conventional shake flask
method as could be seen in the table 1.
Table 1. Solubility of glucosamine, chitosan and alginate
Substances Solvent Solubility
Glucosamine Aquadest freely
soluble
Chitosan glacial acetate Soluble
acid 1,5%
Alginate Aquadest soluble
3.3. Formulation
Nanomaterial of glucosamine was prepared
using the formula with the variation of chitosan and
alginat as shown in the table 2.
Table 2. Formula of nanoparticle glucosamine
Formula F0 FI FII
(mL) (mL) (mL)
Chitosan 0.08% b/v 1 5 -
Chitosan 0.1% b/v - - 5
Glucosamine 0.1% b/v - 1 1
Alginate 0.08% b/v 1 1 1
a b
Figure 1. FTIR spectrum of glucosamine standard (a) and glucosamine sample (b)
Y.A. Prasetyo et al / Indo J Pharm 1 (2019) 1-10
4
a b
Figure 2. FTIR spectrum of chitosan standard (a) and chitosan sample (b)
a b
Figure 3. FTIR spectrum of alginate reference (a) and alginate sample (b)
F0 F1 F2
Figure 4. Physical appearance of the nanomaterial
formulation : F0, Formula I, and Formula II
The physical appearance of prepared
nanomaterial were shown in the figure 4 and
explained in the table 3.
The results of pre-evaluation of glucosamine
nanoparticle size performed by the Uv-Vis
spectroscopy with measuring the % transmittance
and pH during 28 days as shown in the table 4 and
5.
Table 3. Physical evaluation of glucosamine nanoparticle
Formula
0 3 7
Day of
14 21 28
F0
Foggy, no precipitate formed
FI
Foggy, no precipitate formed
FII
Foggy, no precipitate formed
Table 4. Physical evaluation of glucosamine nanoparticles turbidimetry (% transmittance)
Formula
Day-
7 14
Table 5. pH evaluation of glucosamine nanoparticle
Formula
Day-
7 14
0
3
21
28
F0
99.59%
99.43%
99.26%
99.13%
99.08%
99.02%
FI
99.35%
98.87%
98.57%
98.41%
98.35%
98.30%
FII
99.07%
98.83%
98.41%
98.23%
98.17%
97.87%
0
3
21
28
F0
3.00
3.00
3.00
3.01
3.01
3.02
FI
2.90
2.90
2.91
2.92
2.96
2.96
FII
3.05
3.05
3.06
3.05
3.08
3.08
Y.A. Prasetyo et al / Indo J Pharm 1 (2019) 1-10
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Table 6. Characteristic Particle Size, Size Distribution, and Average Size Distribution of Glucosamine
Nanoparticle
Formula Mean particle size (nm)
Particle size (nm) Particle size
*Control = glucosamine standard;
3.4. Characterization
3.4.1.Particle Size Distribution
The result of particle size, size distribution, and
average size distribution of glucosamine
nanoparticle by Particle Size Analyzer (PSA) as
shown in the table 6.
3.4.2. Polidispersity Index
The result of polydispersity index glucosamine
nanoparticle by Particle Size Analyzer (PSA) as
The result of determination of functional groups
of nanoparticles with FTIR shown in the figure 5.
Table 7. Characteristic Polidispersity Index of Glucosamine
Nanoparticle
Formula Polidipersity Index
Control 0.770
F0 0.205
FI 0.300
FII 0.350
Table 8. Characteristic zeta potential and pH value of
glucosamine nanoparticle
shown in the table 7.
Formula zeta potential
(mV)
pH value
3.4.3. Zeta Potential
The result of zeta potential glucosamine
nanoparticle by Zetasizer and pH value as shown
in the table 8.
3.4.4. Determination of Functional Groups of
Nanoparticles with FTIR
Control N/A N/A
F0 N/A 3.00 ± 0.057
F1 -0.30 2.90 ± 0.057
F2 +0.12 3.05 ± 0.057
a b
Figure 5. FTIR spectrum of Glucosamine without nanoparticle (a) and Glucosamine Nanoparticle (b)
D
10
D
50
D
90
distribution (nm)
Control*
2076.6
416.5
507.9
689.6
1076.8±3992.0
F0
479.8
10.7
11.3
13.1
12.3±9.5
FI
396.1
56.0
66.3
96.8
76.0±21.8
FII
384.4
56.7
65.9
94.8
75.7±21.0
Y.A. Prasetyo et al / Indo J Pharm 1 (2019) 1-10
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Table 9. Functional group of glucosamine reference (21) (Nasution, 2013) and sample
Functional Group
Wavelength (cm
-1
)
Sample Reference
O-H
3293.82
3295.60
C-H stretch
2935.13
2942.40
N-H
1538.92
1539.50
C-N amides
1423.21
1422.47
C-N
1249.65; 1184.08
1249.23; 1183.16
Cyclic C-O-C
1095.37
1094.52
Glikosidic bond
1033.66
1033.50
Table 10. Functional group chitosan reference and sample
Functional Group
Sample
Wavelength (cm
-1
)
Reference
Table 11. Functional group of alginate reference and sample
Functional Group
Sample
Wavelength (cm
-1
)
Reference
4. Discussion
Nanoparticles are solid particles dispersed with
a size of 10 - 1000 nm (18). Nanoparticles can be
prepared by top down and bottom up techniques
(19). In this study the formation of nanoparticles
is done through bottom-up techniques because it is
formed by designing atoms or molecules by
combining the particles or clusters to form a
system through nanometer-sized chemical
interactions. Briefly, the teqnique of nanoparticle
formation carried out by dissolution of chitosan
(polymer) using 1.5% acetic acid, then mixed with
alginate (as a crosslinker) dissolved in
aquadestilata resulting in complex polyelectrolyte
bonds forming particles of nanometer size (20).
4.1. Preformulation
4.1.1. Fourier Transform Infrared
Based on the functional groups identified from
the glucosamine sample (Figure 1), the presence of
OH 3293.82 cm
-1
, CH stretch 2935.13 cm-1, NH
1538.92 cm
-1
, CN amide 1423.21 cm
-1
,
Respectively in 1249.65 and 1184.08, cyclic COC
1095.37 cm
-1
, and glycosidic bond 1033.66 cm
-1
.
Therefore it can be concluded that the glucosamine
sample used in this study is in accordance with
reference material as in table 9.
Based on the functional groups identified
from the chitosan sample (Figure 2), the presence
of a primary amine group of 3367.1 cm
-1
, CH
alkana 2919.7 cm
-1
, vibration of NH amide
1650.77 cm
-1
, CH asymmetric CH
3
1427.07 cm
-1
,
and secondary alcohol vibration 1095,37 cm
-1
, it
can be concluded that the sample used is chitosan
according to the reference material as in the table
10.
Based on the functional groups identified from
the alginate sample (Figure 3), OH 3448.1 cm
-1
,
CH aliphatic 2923.56 cm
-1
, COO 1635,34 cm
-1
,
COO 1461,78 cm
-1
, and CO bending 1076,08 cm
-
1
. So it can be concluded that the sample used is
alginate according to the reference material as in
Table 11.
N-H primary amines
3367.1
3454.75
C-H alkanes
2919.7
2923.08
Vibration N-H amida primer
1650.77
1628.87
C-H asymmetric from CH
3
1427.07
1421.52
Vibration C-O secondary alcohol
1095.37
1098.72
OH
3448.1
3420
CH aliphatic
2923.56
2927
COO
1635.34
1620
COO
1461.78
1419
CO bending
1076.08
1096
Y.A. Prasetyo et al / Indo J Pharm 1 (2019) 1-10
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4.1.2. Solubility
The solubility test results of each sample
revealed that 1 gram of glucosamine easily
dissolve in 10 mL aquadestilata (12), 10 mL 1.5%
glacial acetic acid, and practically insoluble in
96% ethanol. One gram of chitosan dissolves in 20
mL 1.5% glacial acetic acid, practically insoluble
in aquadestilate and 96% ethanol (13). One gram
of alginate dissolves in 20 mL of aquadestilate, 20
ml 1.5% glacial acetic acid, and practically
insoluble in 96% ethanol (14).
4.2. Formulation
The choice of chitosan as a polymer is based on
the advantages of chitosan properties including
biocompatible, biodegradable, low toxicity, easily
synthesized and easily characterized. The choice
of alginate as a crosslinker is based on its
properties that can improve the basic structure of
chitosan to form a polyelectrolyte complex (9) and
prevent the destruction of the active compound
glucosamine in chitosan nanoparticles (10). So
that glucosamine will be stable in the chitosan
nanoparticles.
In this study, chitosan used had a deacetylation
degree of 92.30%. The degree of deacetylation of
chitosan will affect the onset of aggregation. The
higher the degree of deacetylation of chitosan, the
lower chitosan acetyl group so that the interaction
between ion and hydrogen bonds is getting
stronger. Thus, at higher chitosan concentrations,
the combined power of chitosan will increase,
which will cause aggregate to emerge and form
precipitate. Based on this, the chitosan
concentration used is below 0.3% to prevent the
formation of particles in micro size (8).
Furthermore, glucosamine nanoparticles were
prepared with chitosan polymer and alginate
crosslinker with ionic gelation. The ionic gelation
is followed by the complexity of different
polyelectrolytes of charge. In this study, chitosan
is a cationic polymer, NH
3
+
, able to react with
multivalent anions of alginate, COO
-
.
Hydrophobic interactions and hydrogen bonds
induced from the amide group (NH
3
+
) that will
contribute to the gelation process. The ionic
gelation process is carried out by mixing the
crosslinker phase, alginate, into the drug-polymer
phase, chitosan-glucosamine dripwise. The
velocity of the droplet is made constant with the
assumption of a particle-generated particle size
distribution. Gupta and Kompella (2006) (22)
explain that in nanoparticles, the force of gravity is
not stronger than Brown motion of particles thus
making the nanoparticles not settle. Sonication
aims to break down compounds or particles of
energy generated by the collapse of cavitation. The
longer the sonication time, the particle size tends
to be more homogeneous and shrink eventually
leading to a stable nanoparticle size and less
agglomeration.
The result of the optimization of the formula
shows that the concentration used has an effect on
the percentage (%) of the transmittance produced.
The optimization result of this formula is the first
step to predict that glucosamine nanoparticles with
chitosan polymer and alginate crosslinker will be
formed at a certain concentration. Measurement of
percent (%) of this transmittance utilizes light-
induced activity by particle due to Tyndall-
Faraday effect. At 0.2% chitosan concentrations
downward, the manufacture of nanometer-sized
particles (nm) is relatively easier to do, with the
effect of alginate concentration on microscale
formation less significant. Expected results are
percent (%) transmitters that are above 99% and
the formation of a clear solution becomes
transparent.
From the results of physical observations then
carried out physical evaluation of nanoparticles to
storage for 28 days. Physical evaluation of
nanoparticles is done as one part to know the
stability of nanoparticles produced. From the
nanoparticle formula evaluation physically, it is
known that the nanoparticle formula undergoes a
change in stability as seen from the value of
transmittance percent (%) which decreases after
day 3, the pH of the formulation changes on day 7,
and the beginning of sediment formation on the
21
st
day. That the F0, FI, and FII are unstable
during storage.
Y.A. Prasetyo et al / Indo J Pharm 1 (2019) 1-10
8
4.3. Characterization
4.3.1. Size and size distribution of particle
The particle size produced was influenced by
the concentration of chitosan polymer and alginate
crosslinker and the active glucosamine agent used,
the minute (minute) of the preparation sonication
of each chitosan and alginate concentration,
velocity (rpm) and time (min), and magnetic stirrer
agitation it shown in table 6.
4.3.2. Polidispersity Index
From the data obtained on glucosamine
nanoparticles with chitosan polymer from the
controls, F0, FI, and FII respectively of 0.770,
0.205, 0.300, and 0.350. This is also in accordance
with Avadi's research, et al.¸ (2010) (23) that the
polydispersity value of the index close to 0
indicates a homogeneous size dispersion and when
it exceeds 0.5, it indicates high heterogenity. The
pH value become acid because its influence by
glacial acetic acid. From these data it can be
concluded that the resulting nanoparticle complex
is still in the range of polarization index values of
theoretical chitosan index and homogeneous size.
While the control has a heterogeneous size.
4.3.3. Zeta Potential
The interaction between particles has an
important role in colloidal stability. The zeta
potential is a measure of the repulsive force
between particles. Most colloidal systems in water
are stabilized by electrostatic forces, the greater
the repulsive resistance force among particles, the
less the particle's ability to combine to form
aggregates. Nanoparticles with zeta potential
values greater than -/+ 30 mV proved stable in the
suspension to prevent aggression (24).
From FI and FII have different zeta potential
charges. The positive or negative value of zeta
potential is influenced by the charge on the surface
of the particles of chitosan containing functional
groups, NH
2
, and alginates containing functional
groups, COOH, which can be ionized. In this study
NH
2
will be ionized with a positive charge and
COOH will be ionized with a negative charge. The
resulting nanoparticle system has a pH<3 which
means that the ionization of the carboxyl group (-
COOH) is inhibited, and the ionization of the
amide (NH
2
) group is increased in accordance with
the pH-partition rule. In general the zeta potential
value is a resultant of cation and anion activity in
the nanoparticle system.
The activity of zeta potential decrease by anion
is reinforced by decreasing pH in nanoparticle
system. The results obtained the more acid pH
medium, the number of base groups (NH
2
) ionized
will be more and more. Increased base groups
(NH
2
) ionized increase the positive charge of the
particle surface, so that negative charge ions will
be absorbed. The higher the zeta potential value,
the more stable the nanoparticles are formed. This
effect is associated with binding of the anionic
group by a long amine group of chitosan to
maintain a high electrical value thereby preventing
aggregation (23).
In addition to its role in determining the physical
stability of the nanoparticles, the resulting zeta
potential will affect its effectiveness in the
glucosamine delivery system. High nanoparticle
loads will facilitate fastening of cell membranes
and high cellular uptake due to the bond between
the polyanionic alginate and the chitosan
polycationic that can facilitate the absorption. The
chitosan cationic compound will increase the
permeation of the skin, with the components of the
phosphatidyl choline and carbohydrate skin tissue
found in mammalian cells containing negatively
charged groups (25). Then it needs to be added into
it stabilizers or surfactants to prevent the particle
size from growing (20).
4.3.4. Determination of functional groups on
nanoparticles with FTIR
On the spectrum shows the reaction between
chitosan and alginate used. The reaction occurs
when through addition and elimination
mechanisms, which alter the functionality of
amides or carboxylates. When in the formation of
nanoparticles reaction occurs between the
carboxylic group (COO-) of alginate and amine
Y.A. Prasetyo et al / Indo J Pharm 1 (2019) 1-10
9
group (NH3 +) of chitosan, then on the IR spectra
there will be absorption in the region of wave
number (cm-1): 1740-1630 (C = O) And 1630-
1510 (NC = O). In the determination of
nanoparticle functional groups, there is known
peak at wavelength 1646,91 (cm-1). This indicates
a reaction between the carboxylic group (COO-) of
the alginate and the amine group (NH 3 +) of the
chitosan. Furthermore there are several peaks of
glucosamine that disappear after the nanoparticles
are made at the wavelengths 3100.97 and 3039.26
(cm-1). This is because glucosamine has been
absorbed in the nanoparticle system, so that
glucosamine functional group readings are
blocked by chitosan polymers and alginate
crosslinkers.
5. Conclusion
The formulation of glucosamine nanoparticles
is influenced by the concentration and volume
ratio of chitosan polymer and alginate
crosslinkers. Comparison of the better volume
ratio of chitosan: glucosamine: alginate = 5: 1: 1.
Comparison of concentrations of 24 formulas
corresponding to the parameters of FI and FII.
Comparison of concentration used FI = chitosan:
glucosamine: alginate = 0.08%: 0.1%: 0.08% and
FII = chitosan: glucosamine: alginate = 0.1%:
0.1%: 0.08%. Further characterization results,
based on physical observation and pH, particle size
and particle size, index polydispersity, and zeta
potential formula I are better than formula 2 with
the result of fog, no sediment, 99.35%
transmittance percent, and PH 2.90 ± 0.5, 396.1
nm; 76.0 ± 21.8 nm, PI 0.300, and zeta potential -
0.30 mV. However, the lack of such a formula is
that the nanoparticles formed are still unstable.
Acknowledgement
We would like to thank Directorate General of
Higher Education, Ministry of Research and
Technology and Higher Education, The Republic
of Indonesia for funding this study. We also thanks
Mr. Jaja and Mrs. Yani from the Laboratory of
Formulation and Pharmaceutical Technlogy,
Universitas Padjadjaran for the technical
assistance.
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