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Eduvest � Journal of Universal Studies Volume 3 Number 1, January,
2023 p- ISSN 2775-3735 - e-ISSN
2775-3727 |
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FORMULATION OF
MUCOADHESIVE TABLETS WITH FULLY GELATINIZED MODIFIED DALUGA (CYRTOSPERMA
MERKUSII) MATRIX USING SIMPLEX LATTICE DESIGN METHOD |
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Gusti Ngurah Agung Dewantara Putra, Made Krisna
Adi Jaya Universitas Udayana, Indonesia
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starch
could used as ingredient fillers, binders and
crushers in tablet manufacture. Amylum is also defined as carbohydrates from from plant, as results photosynthesis, which is stored in
part certain plant as backup food starch is mixture two type structure
different polysaccharides that is contains (17-20) % amylose and (80-83) %
amylopectin. Destination study this is for know the
formulation of mucoadhesive tablets with fully gelatinized modified daluga (cyrtosperma merkusii) matrix using simplex lattice design method. Quantitative
Test Methods that aim for count yield starch and qualitative tests aimed at
for knowing content polysaccharides in starch. Iodine test on amylose will
show color blue, and on amylopectin. Character test result data physique
granules and tablets as well as release ranitidine of tablets analyzed with
using the Design-Expert� software, so that obtained the contour plot of each
test results. Determination of the optimum formula begins with determine the
optimized parameters that is speed flow, tablet hardness, tablet friability,
floating time and speed release ranitidine HCl |
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KEYWORDS |
mucoadhesive
tablets, gelatinized modified daluga (cyrtosperma merkusii), simplex
lattice design method |
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This work is licensed under a Creative Commons
Attribution- ShareAlike 4.0 International |
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INTRODUCTION
Starch
can be used as a filler, binder, and disintegrant in the manufacture of tablets
(Sari et al., 2012). Starch is also defined as carbohydrates derived from plants,
as a result of photosynthesis, which is stored in certain parts of the plant as
food reserves. Physical modification of starch daluga (Cyrtosperma Merkusi) can be done through a fully gelatinized process or what is known as fully gelatinized daluga daluga
(FGDS). Modification of FGDS was carried out by heating daluga
starch above its gelatinization temperature.
The fully gelatinized process can cause amylose to break down,
resulting in more amylopectin components and an increase in gelling ability, larger particle size and higher particle
density. The gel formed from the development
of this matrix acts as a reservoir/gel barrier on the outer surface which is able
to produce controlled release preparations (Sulaiman et al., 2011) .
Controlled release of
the active substance in the digestive tract can be achieved by several methods
namely floating
systems, high density systems,
mucoadhesive systems, extendable
or expandable systems and superporous hydrogels. METHOCEL K4M� is a hygroscopic matrix that
will increase the hardness of the matrix and easily release the drug substance
in the dissolution medium. METHOCEL K4M� apart from having hygroscopic
properties, it is also hydrophilic, so that in large concentrations it will be
easier to interact with the dissolution media (Soemarie and Maulita, 2012).
One of the branches of pharmacy that covers the treatment
of animals or commonly known as veterinary pharmacy. Treatment in animals
differs from humans due to the physiological differences between the two. The
drug delivery system in animals has a very important role so that the drug can
work optimally according to indications and produce the expected response (Ramadhani, 2017).
In this study, a mylum daluga was
physically modified through a fully
gelatinized process then tested for the physical and chemical
characteristics of the starch produced, then the optimum proportion of the FGDS
matrix was combined with METHOCEL K4M� and magnesium stearate which were used
as excipients in tablets. mucoadhesive with
the active substance ranitidine HCl.
The proportion of FGDS, METHOCEL K4M� and magnesium
stearate greatly affects the mucoadhesive system that will be formed and the release of the drug. These problems can be
overcome by an optimization technique approach. One of the optimization methods
that can be used to determine the optimum proportion of a mixture of materials
is the SLD (simplex latice
design) method.
RESEARCH
METHOD
Starch daluga fully gelatinized made with the modified process condition parameters that have
been optimized (Table 1). The ratio of starch: aquadest
is with a ratio of 1: 1 (w/v). The mixture is then stirred until a homogeneous
suspension is formed. The suspension was heated at 80 o C for 15
minutes until a thick mass was formed. The viscous mass was dried in an oven at a temperature of 60 o C
for 48 hours, after drying it was then ground and sieved using a 20 mesh.
Table 1
Fully gelatinized daluga
daluga (FGDS) process conditions
|
Parameter |
Process Condition |
|
fully gelatinized temperature |
80 o
C |
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heating
time |
15
minutes |
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oven temperature |
60 o
C |
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old oven |
48 hours |
������� A certain amount of starch is placed
on a glass object. Then add 1-2 drops of distilled water. Observations of the
hilum, lamellae and arrangement of corn starch were carried out under a
microscope with a magnification of 400x .
������� Quantitative test which aims to calculate the yield of
starch and qualitative test which aims to determine the content of
polysaccharides in starch. Iodine test on amylose will show a blue color, and
on amylopectin will show a blue color
Based
on the data on the results of the physical properties test and the release of
ranitidine HCl from the slow-release tablet preparation with a floating system, it will be possible to
calculate the coefficients of b1, b2, b3, b12, b23, b13 for each test result.
Next is to determine the equation and create a profile of each parameter tested
using the Design-Expert � software,
from each contour plot a superimposed curve
is made so that the optimum formula area is obtained.
The in vivo study was carried out with a single dose crossover design that previously had ethical
clearance as shown in Table 3, using 5
rats. In the first week, rats 1, 3 and 5 were given orally with conventional
ranitidine HCl tablets, while rats 2 and 4 were given mucoadhesive tablets. ranitidine HCl. At week 2-3 all test animals
were rested. At week 4 mice 1, 3 and 5 were given mucoadhesive tablets , mice 2 and 4 were given conventional tablets
(Mayer et al., 1990) .
Table 2
�In vivo test research design mucoadhesive tablets ranitidine HCl
|
Rat |
1st week |
Week 2-3 |
4th week |
|
1 |
kindergarten |
- |
TF |
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2 |
TF |
- |
kindergarten |
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3 |
kindergarten |
- |
TF |
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4 |
TF |
- |
kindergarten |
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5 |
kindergarten |
- |
TF |
Information:
TF ����� = ranitidine HCl mucoadhesive tablets administered orally
TK ����� = conventional tablets of ranitidine HCl
given orally
-
��=
indicates washout time
Data
on the results of the physical properties of granules and tablets as well as
the release of ranitidine from tablets were analyzed using the Design-Expert �
software, in order to obtain a contour plot of each test result.
Determination of the optimum formula begins with determining the optimized
parameters, namely flow rate, tablet hardness, tablet friability, floating time and release rate of
ranitidine HCl. Each test parameter is given a value and the desired target or goal, from each contour plot a superimposed curve is made so that the optimum
formula area is obtained.
The
results of the dissolution test data were made with a curve of the relationship
between the amount of drug dissolution versus
time and the root of time, the regression equation was sought. The
correlation coefficient values of drug dissolution versus time and the roots of time were compared to determine the
kinetics and mechanism of drug release from tablet preparations. The slope
value of the regression equation is the rate of drug release. Drug release
kinetics modeling was made according to: zero
order kinetics, first order kinetics,
Higuchi, Korsemeyer-Peppas and curve fitting with WinSAAM. The data from
the dissolution test also calculated the values of f2 (similarity factor) and f1 (difference
factor).
in vivo absorption test results curves
for the relationship between drug levels in the blood versus time. The calculated parameters include: AUC, C max, t max,
t� elimination and K elimination. The data from the in vitro and in vivo tests were
then analyzed for correlation in vitro -
in vivo (IVIVC). Relative bioavailability is calculated by equation 3.6.
F = (AUC mini floating tablet /AUC conventional
tablet) X 100% ����. (3.6)
The pharmacokinetic parameter data obtained from floating mini tablets and conventional
tablets were analyzed by paired sample
test with a 95% confidence level (Rosa et al.,
1994) .
RESULTS
AND DISCUSSION
The
daluga tubers used in this study were obtained from
the Tabanan area of Bali. The results of the determination of daluga tubers (Figure 16.) with the Latin name Cyrtosperma merkusi Schott including plants belonging to
the family Araceae Juss The
results of the determination are stated in the letter ID number ELSA 53531 on
August 16, 2022 (Appendix 1.). The determination or identification of plants
was carried out in the characterization laboratory of the Bali-BRIN Eka Karya Botanical Gardens. Determination is done to find out
the truth of the identity of the plant, thus errors in the collection of
materials to be studied can be avoided.
Figure 1
�Cyrtosperma
merkusi Schott
The starch
extraction process resulted in a Native daluga daluga (NDS) yield of
30.79% with a water content of 9.38%. yield
The NDS resulting from this process is greater than the yield obtained by Wathoni (2016) which is
15.69%. This difference is caused by differences in the harvesting age of the daluga tubers used. In this study, the daluga
tubers used were 10-11 months old, while those used by Wathoni (2016) were 4-5
months old.
Yield is an
important value in product manufacture. Yield parameters are important to
determine the economic value and effectiveness of a product or material
process. The greater the yield, the higher the economic value of the product,
as well as the value of the effectiveness of the product.
Making starch Natural (Native Daluga)
Natural
starch is made by peeling the daluga tubers and then
washing them with clean water. After that, the daluga
was crushed using a blender with distilled water using the ratio of daluga:aquadest (2:1) w/v. The purpose of using a blender
is to create a mechanical collision between the solvent, namely water and daluga tubers, so that the water is pushed in and the
release of primary metabolites will be even greater. After that, the results
are squeezed and filtered using flannel. The next process is allowed to stand
for 24 hours until a precipitate is formed. The goal is that starch can settle
and not remain in the filtrate so that the resulting starch yield will be
better (Kiptiyah et al., 2021).
The
resulting precipitate was then washed using distilled water until the yield was
obtained in accordance with the description of daluga,
which was white and odorless. The precipitate has a smooth but soft texture
because it still contains water, so it is dried in an oven at a temperature of
50 C to dry
so that the starch produced is protected from the growth of microorganisms (Kiptiyah et al., 2021). The starch produced after drying is in the
form of dry lumps with a fine texture. Sifting was carried out using a mesh
sieve number 100 to obtain a fine powder in accordance with the starch
requirements in the Indonesian Pharmacopoeia Edition IV.
Making starch Fully Gelatinized
The
manufacture of fully gelatinized starch was
made using natural starch (native daluga) obtained and added with distilled water with a
ratio of starch:aquadest (1:1) w/v. After that, it
was heated with steam at 80�C for 15 minutes. A temperature of 80�C is used
because natural starch is gelatinized at a temperature of 68.18�C, so to make fully gelatinized starch, a temperature
above the gelatinized temperature is used but does not damage the amylose and
amylopectin content found in starch (Putra et al., 2018). The result of heating is a bone white
gel which is then dried in an oven at 60�C for 48 hours. The results of heating
from fully gelanitized
starch obtained a hard shape so that it was necessary to reduce the
particle size, then grind and sieve with a 20mesh sieve.
Preliminary Test starch Natural and Modified
Identification starch
Identification
starch aim for ensure as well as identify that materials
used is starch (Arisanti et al., 2014). Identification
test results starch natural and starch fully
gelatinized show results positive with formation color blue old purplish
(appendix 3). Formed color the caused because bonded amylose _ with iodine will
produce color blue and bound amylopectin with iodine Give Bluish Violet Color Or Purple (Priyanta Etc., 2012).
Organoleptic Test
Organoleptic
test conducted for knowing characteristic physique later starch customized with
Indonesian Pharmacopoeia IV edition. Test this cover color, smell, and taste.
Results show that starch natural and starch fully
gelatinized have same feature that is colored white, no smells, and doesn't
taste (appendix 4). That thing already in accordance with Indonesian
Pharmacopeia IV edition (Depkes RI, 1995).
Microscopic Test
Microscopic test aim for observe fragment identifier which is component Specific starch (Partiwisari et al., 2014). The results of observations on starch (attachment 5) have in accordance with Indonesian Pharmacopoeia IV, namely has a hilus located in the middle in the form of point, straight line and branch three as well as lamellae that are not clear (Depkes RI, 1995). starch daluga fully gelatinized has more many arrangement starch the crowd compared with starch experience because existence heating on gelatinization process starch, so that occur damage bond the hydrogen working maintain structure granule starch. Damage bond hydrogen on starch cause water to enter by slowly to in marked granule with development granules. Besides that, warm up could increase swelling starch so that amylose go out and amylopectin permanent trapped in matrix amylose and causes gel formation and push formation arrangement granule clustered starch (Arisanti et al ., 2014).
Macroscopic Test
Macroscopic
test conducted for knowing characteristics and size from starch natural and fully gelatinized. Test this use sieve
graded with mesh no. 20, 40, 60 and 80. Based on results obtained _ namely in
appendix 4, starch experience capable sieved on mesh sieve no. 80 is 97.7 grams
out of 100 grams. That thing already in accordance with Indonesian
Pharmacopoeia IV edition that starch daluga shaped
very fine powder capable of pass sieve mesh no. 80. That thing because starch
experience not yet experience change size particle, so that still in form the
powder. Form powder this classified as fines because could cause capping when printed into tablets (Sari et al., 2012).
starch fully gelatinized belong to powder Rough because capable sieved on a mesh sieve no.20 and many retained on the mesh sieve no. 40. Starch fully gelatinized belong to powder Rough because already experience treatment addition in the form of a gelatinization process namely the process of gel formation due to existence addition of water and heating which causes granule expand and shape something mass thick. Gelatination Process produce starch with more size large (Sari et al., 2012).
Test for Amylose and
Amylopectin Levels
Content test amylose and amylopectin aim for
determine content amylose and amylopectin in starch natural and fully gelatinized. Test earn starch
experience contains 37.25% amylose and 62.75% amylopectin, while starch fully gelatinized contains 25.12%
amylose and 74.88% amylopectin. Test results show that existence upgrade amount
amylopectin in starch fully gelatinized.
That thing because starch at the moment undergo a fully gelatinized process cause amylose broken and components
amylopectin more a lot (Kalogianni et al., 2004). Decrease rate amylose caused because happening disconnection bond
glucoside in the chain amylose, where? chain the is composer part big area easy
amorphous entered the water. When done heating in the modification process,
water enters to in area amorphous and result weak bond hydrogen Among chain
amylose and amylopectin. Weakness bond the result in
the damage crystallinity starch that causes rupture granule starch so that
component amylose will go out from granule starch and components amylopectin
will trapped in the structure matrix amylose (Soebagio and Sriwidodo, 2009)
pH test
test on starch aim for knowing starch pH value natural and fully gelatinized produced already in accordance range namely starch pH experience namely 4-8 and starch pH pregelatin namely 4.5-7 (Rowe et al., 2009). Test results show that starch natural and fully gelatinized already enter good pH range (appendix 8). Results obtained show that starch experience have a higher pH low compared starch fully gelatinized because in the gelatinization process molecule amylose pushed out. Amylose have chain shaped the helix part inside contains H atoms. Reduced molecule amylose in starch cause decline the number of H atoms so that the starch pH will increases, so that in the process of storage will stable and able endure longer (Arisanti et al., 2014).
Moisture Test
The water content is the amount of water contained in declared material _ in percent. High water content could cause starch attached to the surface die and punch at the moment tablet printing. Besides that, high water content could trigger existence reaction enzymatic nor growth microbes that cause occur decay or degradation the compounds present in starch so that could influence stability starch moment storage (Arisanti et al., 2014). The results of the water content test show that starch experience nor starch fully gelatinized already enter condition water content is 15% (w/w) (Depkes RI, 1995).
The test results show there is difference water level is starch fully gelatinized have more water content low compared starch natural (Appendix 9). That thing because the gelatinization process which causes bond hydrogen Among chain amylose and amylopectin weakened and damaged. It's broken bond hydrogen cause during the drying process starch, more water easy miss from group hydroxyl starch and cause drop water content of starch (Arisanti et al., 2014).
and Ethanol Solubility
Test water solubility aims for see solubility starch in water. Solubility test results good starch experience nor starch fully gelatinized show that starch no dissolved (appendix 10). starch shaped particle solid and network the molecule bound through bond hydrogen. In cold water, the particles no will dissolve and break. With existence increase temperature and stirring will produce debilitating energy bond hydrogen, so that water can absorbed by the granules starch and become like a gel. Test solubility ethanol obtained results starch natural and starch fully gelatinized no dissolve. Ethanol is also hard late in starch because particle solid starch, however if heated will into a gel (Putra et al., 2018).
Fourier Transform Infrared (FTIR)
Spectra
Fourier
Transform Infrared (FTIR)
spectra were used to identify functional groups organic compounds. The principle of FTIR is based on the
interaction between the vibrational energy levels (vibration), the vibrations
of atoms bonded in the molecules by
absorbing infrared electromagnetic
wave radiation. The results of the FTIR test are in the form of a spectrum
(attachment 11). Starch daluga is a compound composed
of several components, namely amylose and amylopectin which are composed of CH,
CO, and OH bonds. In natural starch, the CH alkane functional group was
detected at a wave number of 2891.3 cm -1 with an absorption
frequency of 2800-2900 cm -1. The absorption peak of 1159.22 cm -1
was detected by CO bonds with an absorption frequency of 1000-1300 cm -1.
The alcohol OH functional group was detected at a wave number of 3550.95 cm -1
with an absorption frequency of 3200-3600 cm -1. Meanwhile, in
fully gelatinized starch no OH
functional group was detected and CH alkane group was detected at wave number
2883.58 cm -1 and CO functional group at absorption peak 1134.14 cm -1.
The CH bond is an identification of the presence of an aldehyde functional
group, where the aldehyde group is one of the constituent groups of glucose.
Glucose is the basic structure of the formation of amylose and amylopectin
molecules (Kasmawati, 2018). The OH functional group
was not detected in fully gelatinized
starch due to a modification process in starch that is fully gelatinized, resulting in a weakened and damaged hydrogen
bond structure (Arisanti et al., 2014).
Test Metal Weight (Pb, Cd, Fe, As)
Metal heavy could cause effect to health for man depending on the part bound body metal. Metal weight that is poison inside body will endanger health even cause death (Zulharmita et al., 2017). Test metal heavy aim for knowing amount Pb, Cd, Fe, and As content in starch. Test results show that starch natural and starch fully gelatinized no contains Cd (Cadmium) and As (Arsenic). Condition good Pb content that is no more than 1 mg/kg (SNI, 1994). Result of the Pb (Lead) content has been Fulfill requirements ie 0.1998 mg/kg on starch natural and 1 mg/kg on starch fully gelatinized. Besides that, condition good Fe content that is no more than 3 mg/kg (Sumakul, 2019). The content of Fe (Iron) in starch natural and starch fully gelatinized already Fulfill good requirements that is of 0.2603 mg/kg on starch natural and by 0.3445 mg/kg in starch fully gelatinized. Existence content metals (Pb and Fe) due to because storage as well as effect environment like soil, water, and air during the manufacturing process starch (Zulharmita et al., 2017).
X-Ray Diffraction (XRD)
X-Ray Diffraction conducted for knowing level crystallinity starch based on peak
diffraction. There are 3 patterns diffraction X- ray on starch that is The XRD
pattern in type A has peak diffraction strong around 15� and 23� as well as
peak that is not perfect about 17� and 18�; The type B XRD pattern has peak
diffraction strongest around 17� as well as a number of peak small around 15� ,
20�, 22�, and 24�, and peak special at 5.6�; whereas The type C XRD pattern has
nature mixture from type A and type B i.e have peak
strongest around 17� and 23� as well as a number of peak small about 5.6� and
15� (Triwitono
et al., 2017). Based on pattern the resulting diffraction could concluded that
pattern diffraction starch experience that is XRD pattern in type A because
have peak strong diffraction at 15� and 23� and peaks that are not perfect at
17� and 18, whereas starch fully gelatinized no have peak perfect
diffraction (appendix 12). Peak diffraction relate
close with nature crystallinity from starch (level amylose and amylopectin).
Starch is ingredient semicrystalline containing area crystalline and amorphous.
starch fully gelatinized have level more crystallinity low compared
starch natural. That thing caused because increase content amylopectin
due to the modification process. The more many amylopectin, then area amorphous
will the more broad and cause area crystalline the
more narrow. starch arranged from amylopectin located in the region amorphous
and amylose which are in the region crystalline. (Haryani et al., 2022).
Scanning Electron Microscope (SEM)
Scanning Electron Microscope (SEM) is a a microscope designed electrons _
for observe surface object by direct with magnification 10-3,000,000 times.
Test this aim for see form surface starch with resolution high. Results show
that starch experience shaped particle small no hollow and regular. Whereas
starch fully gelatinized shaped particle big hollow and amorphous
(appendix 13). This thing caused by the modification process because content
amylose and amylopectin play a role in control size and shape granules (Sakinah and Kurniawansyah,
2018).
Physical Properties Test starch Natural and Amylum Modification
Flow Properties Test
a.
Flow Time
Flow
time is time required amount granule for flow pass declared funnel as a lot
flowing powder each unit time (Elisabeth et al., 2018). Time test results flow show that on starch experience no could flow
pass funnel (appendix 14). That thing because size small particles so that
cause no existence cavity air between particles. Meanwhile, in starch fully gelatinized have nature good flow ie 12.29 � 0.09 g/ second and already enter range of 4
gram/ second (Sari et al ., 2012).
b.
Angle of Still
The
angle of repose is corner formed Among -shaped powder cone with field flat.
Measurement silent corner done with compare Among tall cone powder formed with
diameter (Rohmani
and Rosyanti, 2019). Test results
angle of repose in starch experience show that starch no capable pass the
funnel that causes angle of repose no could calculated. Meanwhile, in starch fully gelatinized generated angle of
repose is 26.21�
� 0.30 (appendix 14). The result already enter range good still angle i.e. 25˚-30˚ (Arisanti et al., 2014).
Compressibility Test
Compressibility
test aim for determine nature materials that can shape stable and compact mass
when given pressure (Nurjanatun and Balfas, 2019). Results show
that starch experience have index compressibility as big as 21.60 � 0.47%,
while starch fully gelatinized has index compressibility of 12.49 �
1.56% (appendix 15). Compressibility value starch experience morebig compared with starch fully gelatinized
because starch experience have size more particles
small compared starch fully gelatinized. Compressibility value affected by
distribution size particles. The more small size
particle so score score resulting compressibility the more big. If
seen from nature the flow, the more small score compressibility so nature flow
will the more good (Sari
et al., 2012).
Granules
were made by wet granulation method. Wet granulation is a process of mixing the
active substance and excipient particles into larger particles by adding the
right amount of binder liquid so that a moist mass can be granulated. The
principle of this method is to wet the mass or mixture of active substances and
excipients with a binder solution until a certain level of wetness is obtained (Gopalan and Gozali, 2018).
Table l2
The design of the
mucoadhesive tablet formula using the simplex lattice design method which is
processed computationally using Design Expert software
|
Run |
Ingredients
(mg)/tablet |
||
|
FGDS (X 1 ) |
HPMC K4M
(X 2 ) |
Mg
stearate (X 3 ) |
|
|
1 |
76.67 |
36.67 |
6.67 |
|
2* |
80.00 |
40.00 |
0.00 |
|
3 |
78.33 |
33.33 |
8.33 |
|
4 # |
75.00 |
35.00 |
10.00 |
|
5 |
80.00 |
35.00 |
5.00 |
|
6* |
80.00 |
40.00 |
0.00 |
|
7 _ |
80.00 |
30.00 |
10.00 |
|
8 _ |
80.00 |
30.00 |
10.00 |
|
9 _ |
70.00 |
40.00 |
10.00 |
|
10 _ |
70.00 |
40.00 |
10.00 |
|
11 |
75.00 |
40.00 |
5.00 |
|
12 |
78.00 |
38.33 |
3.33 |
|
13 # |
75.00 |
35.00 |
10.00 |
Physical Properties Test Granule
Particle Size Distribution
The
particle size distribution test uses the most commonly used method, namely the
sieving method because it is cheap and simple. This method serves to measure
the particle size distribution by using a sieve mesh arranged in succession, where the coarsest sieve mesh is
placed at the top (Jannah et al., 2018; Mulyadi et
al., 2011). The
importance of this test because the particle size can affect the flow rate of a
granule. The finer the particle size, the lower the flow rate. Granules that
are more distributed at a certain size indicate the quality of the granules
(particle size uniformity) is quite good as a raw material for tablet printing.
The results showed that all formulas had a particle size distribution with a mesh size of 20 and the most retained by
a 40 mesh sieve (appendix 19). This is because
the granulation process is carried out using a 20 mesh sieve. The concentration of the binder affects the particle
diameter, so that more binders will produce small particle diameters and fewer
fines (Mulyadi et al., 2011).
Compressibility
Compressibility
testing aims to measure the density of the granules to facilitate tablet
printing because tablets that have a good percent compressibility will be
easier to compress. The results of the compressibility test show that the
percent compressibility index of all formulas meets the requirements well,
which is below 20%. The size of the compressibility is influenced by the shape
of the granules and the size of the granules (Devi et al.,
2018; Yulisani et al., 2020). The
smaller compressibility percentage indicates the ease of granules in tablet
compression so that a more compact tablet is produced compared to formulations
that have a high compressibility percent. Compressibility will also affect the
flowability of the granules. The presence of wetting can increase the
compressibility of the granules. This is due to the strong bonds between
particles so that the granules can be well compressed (Devi et al., 2018).
Flow time
Flow
time is the time required for a number of granules to flow through the funnel
which is expressed as the amount of powder flowing per unit time. The results
of the flow time test showed that all the formulas had met the good
requirements, namely 10 grams/second. The nature of the flow is influenced by
the shape of the particles as well as the size of the particles. Good granules
are granules that can flow freely so they can be compressed into tablet
preparations. The smaller the concentration of the binder, the more the
particle size makes it difficult for the granules to flow freely (Elisabeth et al., 2018). Granules with poor flow will cause the
flow of granules from the hopper to
the die is not perfect, as a result
the resulting tablet weight is not constant (Putra et al.,
2019)
Quiet angle
The
angle of repose is a fixed angle that occurs between the pile of conical
particles and the horizontal plane when a certain amount of powder is poured
into the measuring device. The granules will form a cone, the flatter the
resulting cone, the smaller the angle of repose is (Husni et al., 2020; Mulyadi
et al., 2011). The results of the angle of repose test
show that all formulas have entered the requirements of a good angle of repose,
namely the angle of repose if 30� then the powder is able to flow well, but if
40� then the flow properties are not good. The smaller the angle of repose the
better the flow properties of the granules so that the tablets have a uniform
weight uniformity. The value of the angle of repose is related to the flow
time, where the faster the flow, the smaller the angle of repose formed (Rohmani and Rosyanti,
2019).
Granule moisture content
The
moisture content test was carried out to determine the amount of volatile
substances including water contained in the instant granules due to the heating
process that occurred in the granules at the time of drying (Husni et al, 2020). The
results obtained from testing the moisture content of the granules are that all
formulas have entered the criteria for a good granule moisture content of 5% so
that it will produce good and stable granules during storage (Rowe et al., 2009).
Tablet Manufacturing
Making
tablets is seen based on the results of testing the physical properties of the
granules. Based on the test results, all formulas have met all the requirements
so that they can be compressed into tablets because they are in a good range of
requirements. Tablet printing uses a single
punch set up. The main requirement for making tablets is that the
components are easy to compress and flow easily. Tablet components that have
good flow properties and compressibility index will experience changes in shape
and volume more when given an external mechanical force (Lachman et al., 1994).
CONCLUSION
Modification starch Becomes Fully
gelatinized starch can be used as mucoadhesive tablet excipients. That thing
proven in research this that is fully gelatinized starch has size
more particles big compared starch experience so that cause fully gelatinized
starch has nature more flow good. Flow properties take effect to mucoadhesive
tablet manufacture because good granule that is granules that can be flow free
so that could compressed Becomes tablet preparation.
Combination of FGDS, HPMC K4M and
mg stearate give influence to hardness test response Y = (+0.056374) (A) +
(+0.035041) (B)+ (-0.021404) (C), brittleness test response Y = (-1.37491E-005)
(A) + (+2.18064E-005) (B) + (+3.46251E-005) (C), mucoadhesive test response Y =
(+0.12141) (A) + (+0.068080)(B) + (-0.091920)(C) and response to dissolution
test Y = (-0.023471) (A) + (+0.073374) (B) + (+0.46146) (C). Combination
results of FGDS, HPMC K4M, and mg stearate with comparison (300:150:105) set as
the optimal formula with desirability value 0929; with score prediction violence
19.921; brittleness 0.036; mucoadhesive 36,985; and dissolution 52.419.
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