Vol 2, Issue 3, 2020 (104-111)
http://journal.unpad.ac.id/idjp
*Corresponding author,
e-mail : dolih.gozali@unpad.ac.id (D. Gozali)
https://doi.org/10.24198/idjp.v2i3.31561
© 2020 D. Gozali et al
Formulation of Coated Tablets Film Of Jengkol Fruit Seeds (Pithecellobium lobatum Benth.) as A
Selenium Herbal Supplement
Dolih Gozali
1
*, Mutakin
2
, Yunita
1
, Norisca Aliza
1
1
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas
Padjadjaran, Bandung, Indonesia
2
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas
Padjadjaran, Bandung, Indonesia
Received : 01 Aug 2020, Revised : 11 Sept 2020, Accepted : 08 Oct 2020, Published : 21 Oct 2020
ABSTRACT
The correlation between the high content of selenium (Se) in plasma and the low prevalence
of cardiovascular disease has been published in previous epidemiological studies. The
content of Se in the plasma is determined by daily intake. A preliminary surveillance of Se
content of several plants showed that the seeds of jengkol (Pithecellobium lobatum Benth.)
has the highest concentration of Se. This study aims to develop a pharmaceutical
formulation of Se supplement for adjuvant therapy of cardiovascular disease. The jengkol
seeds was made into film coated tablets with a wet granulation method. Optimization of the
core tablet formula was carried out with variations of binder concentration and coating
material. Evaluation was carried out on uniformity of size and weight, disintegration time,
hardness and friability. The content evaluation was carried out including the levels of Se,
water content, ash, fat, protein, carbohydrate and crude fiber. The results showed that the F3
had the lowest friability and highest hardness. The coating of tablets using PVA has covered
the smell of jengkol seed. The evaluation results showed that film coated tablets contained
the Se level content of 0.074 ± 0.004 µg/g, water content of 2.19%, ash content of 1.88%, fat
content of 0.89%, protein content of 0.66%, carbohydrate content of 94.38% and crude fiber
content 1.79%. The results showed that the jengkol seed film coated tablet formulation could
be used as a supplement in additional therapy for cardiovascular disease.
Keywords : Pithecellobium lobatum, film coated tablet, herbal supplement, selenium
BACKGROUND
The jengkol plant is a typical plant that grows in
Southeast Asia, including in Indonesia. This
plant includes plants that are commonly eaten
(edible plant). The used and consumed part of
this plant is the seeds. Jengkol fruit seeds are
commonly consumed by Indonesians, including
those in West Java. The nutritional content
contained in jengkol fruit seeds includes vitamin
C, jencolic acid, tannins, flavonoids and
saponins (1). Jengkol fruit seeds have a
distinctive and pungent odor due to the presence
of the amino acid cysteine which contains sulfur
(2). Some plants contain Selenium (Se), one of
which is the jengkol plant. It is necessary to first
determine the Se content in the seeds of jengkol
fruit to determine the range of Se content in the
seeds of jengkol fruit because so far there has
been no research that has conducted the
determination of the Se content in the seeds of
the jengkol fruit.
Se is a micronutrient needed by the body. The
organic and inorganic forms of Se serve as a
source of the mineral Se for the body. Se intake
can be obtained from food, drinks or in the form
D. Gozali et al / Indo J Pharm 3 (2020) 104-111
105
of Se supplements (3). Foods that have been
known to contain Se include meat, seafood,
dairy products, onions and others (3
.
4. The Se
content in plants is strongly influenced by the
Se content in the soil, so that there can be
differences in the content in plants depending on
the area where it is grown (5).
The recommended amount of selenium intake
per day is 55 µg / day and the maximum
tolerance limit is 400 µg / day. The amount of
the need for each individual depends on sex,
age, pregnancy and geographic area (6). If in
deficiency conditions it can cause Keshan
disease, Kashin-Beck disease, thyroid disorders,
cancer, cardiovascular disease, and reproductive
problems. Meanwhile, if it exceeds the
maximum limit it can cause toxicity (7). There
has been research that proves that there is an
inverse correlation between the prevalence of
cardiovascular disease with the Se concentration
in rice consumed and the nutritional status of
Se, where the areas with the highest Se
concentrations have the lowest prevalence of
cardiovascular disease, stroke and hypertension
(8). In addition, in Indonesia the prevalence of
cardiovascular disease and stroke is very high,
namely 12.1% (9). According to WHO,
cardiovascular disease is the number one cause
of death in the world (10). So that Se has an
important role for human health and to
overcome differences in Se intake in areas with
low levels of Se in soil, Se supplementation can
be one of the supportive therapeutic solutions.
Because a good supplement is a supplement
with food, food sources that are rich in Se are
used as raw material for supplements, namely
jengkol fruit seeds.
The unpleasant smell of the jengkol fruit seeds
causes some people to dislike consuming them.
So that from this background, it is necessary to
formulate the film-coated tablet dosage form of
jengkol fruit seeds to cover the odor of tablets
and increase consumption interest. Tablets were
prepared using the wet granulation method and
with a PVA coating solution.
METHODS
Jengkol seed preparation. Jengkol fruit seeds
were collected from 15 districts / cities in West
Java which had been determined by random
sampling method. Jengkol seeds were mashed in
a blender and weighed as much as 400 mg to
digest with 2 ml of nitric acid: perchloric acid
(2: 1) for 8 hours. Then 0.5 ml of 10 N HCl
solution was added and heated again for 20
minutes at a temperature of 150°C and then
cooled.
Formulation of Jengkol Seed Core Tablets.
The inner phase consists of jengkol seed
powder, lactose, 5% amprotab, and 12.5%
starch paste. Starch paste solution is added
gradually to the mixture of jengkol seed
powder, lactose, and ampoule until a mass is
formed.
which can be clenched, then sieved using mesh
number 16. Drying is perfomed by using an
oven at a temperature of 40 - 50°C for 18 hours.
The outer phase (5% ampoule, talc and
magnesium) is added to the dry granule. The
print mass was evaluated by LOD testing, bulk
density, compressible tap density,
compressibility, flow rate and angle of rest. The
printed mass is then printed using punch number
13 with a maximum weight of 650 mg per
tablet.
Table 1. Jengkol seed core tablet formula
Ingredient
Formula (%b/b)
1
2
3
Jengkol Fruit Seeds
20
20
20
Amprotab
10
10
10
Starch Paste
2
3
5
Lactose
65
64
62
Talc
2
2
2
Mg Stearate
1
1
1
Coating tablets. Coating solutions are prepared
by dissolving the ingredients in Table 2 in 900
grams of water at a temperature of 90
°C
-95
°C
.
Then the coating is done using the pan coating
method.
D. Gozali et al / Indo J Pharm 3 (2020) 104-111
106
Table 2. Coating Solution Formula
Ingredient
Formula
(%)
Polyvinyl alcohol
40
Propylenglycol
10
Glyceryl
Monostearate
20
TiO
2
20
Apple Green L.T
10
The evaluation of core tablets and coated tablets
included organoleptic test, diameter, thickness
and uniformity of weight, hardness, friability,
and tablet disintegration test. In the coated
tablet, additional evaluation was carried out,
namely the percent increase in weight,
determination of Se content and proximate
analysis and crude fiber content.
Determination of Se content in the
preparation.
20 tablets were crushed and weighed as much as
400 mg because the sample had low Se content
(vegetables) (11) to be digested with 4 ml of
nitric acid: perchloric acid (2: 1) for 8 hours.
Then 0.5 ml of 10 N HCl solution was added to
reduce selenate (SeO
42
-) to selenite (SeO
32
-)
and heated again for 20 minutes at 150
C
0
and
then cooled. After that, 0.1 ml of 0.1 ml EDTA
solution was added as a chelating agent that
would bind other metals which could interfere
with the measurement (12); 20 µl of 1% thymol
blue solution until the solution turns red. 25%
NH4OH was added (in the water bath) until the
color turned blue and 2N HCl was dropped until
the solution turned pink. 1 ml of 0.1 N HCl, 1
ml of 2.3-DAN 0.1% solution at 50°C while
shaking for 10 minutes. The formation of
selenium complexes with 2.3-
diaminonaphthalene 0.1% (AND 0.1%) forms
4.5-benzopiazselenol compounds or can be
referred to as nafto-2-selena-1.3-diazole 12).
When finished, the tubes were cooled to room
temperature (to allow the Se3 + and 2.3-DAN
reactions to occur). After cooling, 2 ml of
cyclohexane were added, covered, shaken for 2
minutes and centrifuged for 5 minutes at a speed
of 2500 rpm. The cyclohexane part was taken as
much as 100 µl and put into the microplate
well-96 and the intensity was measured with
excitation 378 nm and emission of 525 nm on a
fluorometer.
Proximate analysis and crude fiber content in
film coated tablets.
Proximate and crude fiber analysis was carried
out at the Test Laboratory of the Faculty of
Agricultural Industrial Technology, UNPAD.
Analysis of the fat content of the Soxhlet
method, the protein content of the Kjeldahl
method, the water content of the gravimetric
method and the ash content were carried out by
the test methods listed in SNI 01: 2891: 1992.
The analysis of carbohydrates was carried out
using the method by difference, namely by
reducing 100% the moisture content, ash
content, protein content, and fat content. While
the analysis of crude fiber content was carried
out by the hydrolysis testing method.
RESULTS AND DISCUSSION
The jengkol fruit seeds tested came from 15
different regions in West Java. Measurement of
Se content in jengkol fruit seeds was carried out
using the Watkinson method. This method
measures the selenium content in the acid
digested sample using a fluorometer.
From the measurement results, the highest Se
content was found in jengkol fruit seeds from
Subang Regency (Sagalaherang Market),
namely 0.4980 ± 0.0666 µg / g. Differences in
Se content in jengkol fruit seeds from different
areas may occur due to differences in Se content
in the soil where the jengkol grows. So far there
has been no research on the analysis of Se
content in jengkol fruit seeds, so there is no
comparable range of Se levels. However, when
compared with other vegetables such as garlic
[0.021 µg / g (13)]; cabbage [0.002-0.014 µg / g
(14)]; petai (0.0242 - 0.2579 µg / g) and spinach
D. Gozali et al / Indo J Pharm 3 (2020) 104-111
107
[0.024 µg / g (15)], the Se content in the seeds
of jengkol fruit is very high. So that it can be
used as a raw material for making herbal
supplements Se.
The wet granulation method was chosen
because the jengkol used was still a wet material
so that this method could simultaneously reduce
the water content in the jengkol and also to
obtain a good flow rate. The binder used was
starch paste 12.5% with a concentration
variation of 2% (F1); 3% (F2) and 5% (F3). The
concentration of starch paste commonly used as
a tablet binder is 3-20% (16). In order to
determine the best binder concentration,
evaluation was carried out on the resulting print
and tablet mass.
Table 3. Results of Mass Evaluation of Tablet
Testing
F1
F2
F3
LOD (%)
0.10
0.12
0.55
Angle of
repose (
o
)
16.27±
4.41
12.51 ±
2.06
12.15 ±
1.93
Flow rate
(g/s)
20.48 ±
6.36
14.09 ±
2.13
33.97 ±
5.74
Compressibil
ity (%)
19.00 ±
0.026
20 ±
0.012
21 ±
0.018
LOD = lost of drying
The LOD value from the print mass evaluation
results shows the water content contained in the
print mass. The requirement for the LOD value
is <1-2%. The result is that F3 has the highest
LOD value, namely 0.55%.
The results of the evaluation of the angle of rest
for the three formulas are less than 25o, which
means that the three formulas have very good
angles of rest. However, F3 has the best angle of
rest and has the best flow rate of 33.97 g / s. The
flow rate and angle of rest of the print mass will
affect the ability of the granules to flow through
the hopper during the printing process and affect
the uniform weight of the tablets.
The ease of the print mass to be compressed into
a tablet can be seen from the compressibility
value. The compressibility value of the three
formulas falls into the moderate category,
namely 18-22%. But F1 has the lowest
compressibility among all formulas.
Table 4. Tablet Evaluation Results
Parameters
F1
F2
F3
Weight (mg)
654.71 ±
30.20
662.48
± 17.64
657.31 ±
10.93
Thickness
(mm)
5.24 ±
0.07
5.19 ±
0.07
5.17 ±
0.07
Diameter
(mm)
13.12 ±
0.03
13.05 ±
0.02
13.09 ±
0.02
Hardness (N)
33.25 ±
9.35
48.25 ±
11.12
49.5 ±
5.83
Disintegration
time
(minutes)
1.80 ±
0.251
1.68 ±
0.33
1.92 ±
0.48
Friability (%)
1.42±0.010
1.33
±0.012
0.42±0.01
After all granular mass were compressed by
tableting process then its quality were evaluated.
The core tablets produced from F1, F2 and F3
have a round biconvex shape, are white in color
with brownish spots and smell of jengkol which
can be seen in appendix 3. This shape is in
accordance with the ideal core tablet shape for
coating, namely elliptical, round bikonvek or
oval bikonvex. and spherical (17).
The results of the F1, F2 and F3 weight
uniformity tests in Appendix 4 meet the
requirements because no two tablets deviate by
5% and none of the tablets deviates by 10%
from the average weight of the tablets.
Likewise, from the results of the size uniformity
test, tablets from F1, F2 and F3 meet the
requirements because they have a diameter not
more than 3 times and not less than 4/3 the
thickness of the tablet (9). In the hardness test,
tablets with F1 had the lowest hardness and did
not meet the requirements because they were
less than 40 N. Whereas tablets with F2 and F3
D. Gozali et al / Indo J Pharm 3 (2020) 104-111
108
met the hardness requirements because they
were between 40-80 N. The hardness of the
tablets could be affected by the amount of
punch pressure in the tableting process.
The result of the disintegration time test showed
that all formulas meet the requirements because
the tablet disintegration time is less than 15
minutes. The duration of disintegration is
influenced by the concentration of the binder
and is directly proportional to the hardness of
the tablet. Tablets with higher hardness will
have longer disintegration times. Because the
coating process will be carried out on the tablet,
the friability test is very important to do. The
result of the three formulas, only F3 meets the
friability requirements because <1% is equal to
0.412%.
Through the binder optimization process, the
results showed that F3 with a starch paste binder
concentration of 5% produced tablets with the
highest hardness and lowest friability. So then
the production of core tablets was made by
using F3. Production of tablets was made in 3
batches with 250 tablets each. During the
production process, evaluation of the mass of
compressed tablet and evaluation of core tablets
were also carried out.
The results of the LOD test on the tablet print
mass met the requirements and the results were
close to the LOD value of the F3 formula at the
optimization stage. The resulting print mass has
a flow rate and an angle of rest that fall into the
very good category. But it has enough
compressibility because it is between 18-22%.
After the mass evaluation process is carried out,
then the print mass is compressed using punch
13 to produce the core tablet. The resulting core
tablet has a round biconvex shape, is white with
brownish spots and smells of jengkol.
Furthermore, the evaluation of tablets includes
weight uniformity, size uniformity, hardness,
disintegration time and friability.
Based on the results of the weight uniformity
test (data not shown), the tablets meet the
weight uniformity requirements because no two
tablets deviated by 5% and none of the tablets
deviated by 10% from the average weight of the
tablets. Likewise, from the results of the size
uniformity test, tablets meet the requirements
because they have a diameter of no more than 3
times and or not less than 4/3 the thickness of
the tablet (9). The value of tablet hardness at the
production stage is not much different from the
optimization stage, but is smaller than the
optimization stage. The difference in hardness
can occur due to the different amount of punch
pressure during the printing process. But the
hardness of the tablet meets the requirements
because it is between 40-80 N, which is 45.95 ±
2.47 N.
Figure 1. Physical Appearance of Jengkol Fruit
Seed Core Tablets
The tablet disintegration time met the
requirements because of the six tablets used in
the disintegration test all of them disintegrated
in less than 15 minutes for an ordinary,
uncoated tablet. The disintegration time can be
affected in part by the hardness of the tablet.
Because tablets at this production stage have
less hardness, they will have a faster
disintegration time than the same formula in the
optimization stage. Another important
evaluation for the tablet to be coated is
friability. The hardness or friability of tablets is
related to the hardness of tablets, because
generally tablets with high hardness have low
friction. If the friability of the core tablet is too
high then the released fine particles will stick
D. Gozali et al / Indo J Pharm 3 (2020) 104-111
109
with the coating droplets on the tablet surface
during the coating process which will cause the
coating layer formed to become rough and
uneven. The result is that the tablet friability
meets the requirements because it is less than
1%. Furthermore, the coating process is carried
out on the core tablet with the printed F3
formula.
Table 5. Results of Mass Evaluation of Tablet
Print in the Production Stage
Testing
Result
LOD (%)
0.41 ± 0.26
Angle of Repose
(
o
)
14.18 ± 2.49
Low rate (g/s)
101.85 ± 13.98
Compressibility
(%)
19 ± 0.017
The purpose of tablet coating in this formulation
is to mask the unpleasant odor of the tablet
preparation. The polymer used as a coating is
polyvinyl alcohol. The use of propylenglycol
and glyceryl monostearate in coating solutions
functions as a plasticizer and emulsifying agent.
The plasticizer functions to prevent the film
from becoming brittle and minimize defects in
the coating layer (18), while the emulsifying
agent functions so that the coating solution can
mix homogeneously and stick to the tablet
surface. In the coating solution formula,
titanium oxide and apple green coloring are also
added to make the preparation more attractive.
The physical appearance of the film coated
tablets is round bikonvex, green in color with a
less pungent jengkol odor. Coating is carried out
until the increase in tablet weight is in the 2-5%
range. The result is an increase in tablet weight
of 2.6% fulfills the requirements because it is in
the 2-5% range (19). But not enough to cover up
the smell of the tablet. So that a further coating
process can be carried out, because the thicker
the coating layer, the more it will cover the
smell of the tablet.
Table 6. Evaluation Results of Core Tablets in
the Production Stage
Parameters
Results
Weight (mg)
643.8 ± 5.9
Thickness (mm)
5.07 ± 0.036
Diameter (mm)
13.09 ± 0.039
Hardness (N)
45.95 ± 2.474
Disintegration
time (minutes)
1.51 ± 0.087
Friability (%)
0.724 ± 0.011
Table 7. Physical Evaluation Results of Film
Coated Tablets
Parameters
Results
Weight (mg)
663.4 ± 11.5
Thickness
(mm)
5.40 ± 0.208
Diameter
(mm)
13.19 ± 0.038
Hardness (N)
46.183 ± 1.765
Disintegration
time
(minutes)
3.46 ± 0.413
Friability (%)
0.088 ± 0.0003
Increase in
weight (%)
2.6 ± 0.002
Table 8. Evaluation Results of Chemical
Content of Film Coated Tablets
Parameters
Results
Se content (µg /
g tab)
0.074 ± 0.004
Water (%)
2.19 ± 0.003
Ash (%)
1.88 ± 0.005
Protein (%)
0.66 ± 0.002
Fat (%)
0.89 ± 0.001
Carbohydrate
(%)
94.38 ± 0.012
Crude fiber (%)
1.79 ± 0.003
The coated tablet has a greater average weight
than the core tablet. Theoretically the final
coated tablet would weigh 660.5 mg. Based on
the results of the weight uniformity test (data
not shown), the tablets met the requirements
D. Gozali et al / Indo J Pharm 3 (2020) 104-111
110
because there were no two tablets whose weight
deviated by 5% and not a single tablet had 10%
deviating weight from the average weight of the
tablets.
Figure 2. Physical Appearance of Jengkol Fruit
Seed Film Coated Tablets
The coating process also causes an increase in
the diameter, thickness, hardness and crush time
of the tablets. However, the size of the tablet
still meets the requirements because it has a
diameter that is not more than 3 times (16.2
mm) or not less than 4/3 the thickness of the
tablet (7.2 mm). The hardness of the film coated
tablet still meets the requirements because it is
in the range of 40-80 N. The increase in tablet
hardness occurs because wat
er from the coating solution that enters the tablet
will increase the compactness of the tablet so
that the tablet becomes harder. Film coated
tablets have a longer disintegration time than
core tablets because of the polymer coating the
tablet surface so it takes longer time for the
tablets to dissolve. In the coating process, the
pores on the tablet surface are covered by a
coating solution so that it will slow down the
penetration of the liquid when crushed (20). The
yield of the disintegration time of film coated
tablets was 3.46
CONCLUSION
Based on the evaluation of compressed mass
and tablet quality at the optimization stage, the
F3 formula has the lowest tablet friability value
and the highest tablet hardness. The formula for
the film coated tablet of jengkol fruit seeds
(Pithecellobium lobatum Benth.) used the F3
formula (5% starch paste binder) with the
coating solution used is PVA to cover odors.
The results of the physical evaluation of the
jengkol seed film coated tablets met the
pharmacopoeial requirements and the film
coated tablets contained Se of 0.074±0.004
µg/g; water content of 2.19%; ash content of
1.88%; fat content of 0.89%; protein content of
0.66%; carbohydrate content of 94.38% and
crude fiber content of 1.79% but coating the
tablets using PVA could not cover the smell of
the initial raw material.
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