Volume 03 Issue 12-2023
6
American Journal Of Biomedical Science & Pharmaceutical Innovation
(ISSN
–
2771-2753)
VOLUME
03
ISSUE
12
P
AGES
:
6-13
SJIF
I
MPACT
FACTOR
(2021:
5.
705
)
(2022:
5.
705
)
(2023:
6.534
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
ABSTRACT
Previous research has investigated the technological properties of the dexketoprofen trametamol substance and has
been shown to be negative. For this reason, the article covers research on the selection, technology development of
a complex of various auxiliary substances for the development of a capsule drug form based on the substance
dexketoprofen trametamol. In it, the size of the capsule was determined on scientific basis, based on the scattering
density of the substance, and encapsulated masses were prepared using various excipients. As a result of determining
the technological properties of these compositions as well as the quality indicators of the capsules obtained, the
optimal composition was selected and the capsule technology was developed, in which the dexketoprofen
trametamol substance was stored.
KEYWORDS
Deksketoprofen trometamol, substance, capsule, technology, excipients, composition, technological properties.
INTRODUCTION
Research Article
DEKSKETOPROFEN
TRAMETAMOL
CAPSULE
DRUG
FORM
COMPOSITION SELECTION AND TECHNOLOGY DEVELOPMENT
Submission Date:
December 01, 2023,
Accepted Date:
December 05, 2023,
Published Date:
December 10, 2023
Crossref doi:
https://doi.org/10.37547/ajbspi/Volume03Issue12-02
M.K.Usmonova.
Assistant, Tashkent Pharmaceutical Institute, Uzbekistan
F.X.Maksudova.
Associate Professor (Dsc), Tashkent Pharmaceutical Institute, Uzbekistan
A.M.Usubbaev
Associate Professor (Phd), Tashkent Pharmaceutical Institute, Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ajbspi
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
Volume 03 Issue 12-2023
7
American Journal Of Biomedical Science & Pharmaceutical Innovation
(ISSN
–
2771-2753)
VOLUME
03
ISSUE
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P
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:
6-13
SJIF
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(2021:
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OCLC
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1121105677
Publisher:
Oscar Publishing Services
Servi
Adaptation of highly effective, stable and high-quality
medicines produced in foreign countries to the
practice of domestic production without affecting
their quality and, thus, partial provision of the domestic
market of the Republic of Uzbekistan with high-quality,
affordable and necessary medicines is one of the most
important and urgent tasks facing pharmaceutical
technologists. [1,2].
Today, capsules occupy a special place among ready-
made medicines and occupy the third place in
pharmaceutical
production
after
tablets
and
ampoules. [8].
Capsule types of medicines are the leaders among
ready-made medicines produced on an industrial scale.
The main reason for this is a number of advantages of
the capsule type of medicine: accurate dosage, rapid
action on the div, the fact that the medicinal
substance is protected from exposure to light,
moisture, air, its stability is ensured, the unpleasant
smell and taste of the medicinal substance are
disguised, dyes and easily pollinated substances can be
used when air moves, as well as high bioefficiency, as
well as the ability to prolong the action of the active
substance and use it for what has control capabilities
[4,7].
Many synthetic drugs have the property of tickling the
mucous membrane of the gastrointestinal tract, and
when taken for a long time, the wound can become a
dressing. Also, some active substations lose their
effect from the action of acid in gastric juice. Even in
such cases, it is advisable to apply gelatin capsules.
Such capsules will be intended for dissolution in the
intestine, that is, they will not decompose under the
action of acid from gastric juice[8].
Based on the results of research carried out by many
scientists in recent years, the absence of a pressing
process in the development of the capsule drug form
ensures that they decompose faster than tablets and
dragees and are absorbed into the div faster, and
pharmacotherapeutic activity Ham manifests much
faster [3].
The purpose of the study. Taking into account the
above, the goal was set to develop a capsule drug form
of dexketoprofen trometamol substance.
Experience part
Research methods and tasks. In our scientific research,
we used the substance deksketoprofen trametamol
(NN 42 Uz-8979-2018). This substance is a white
crystalline powder, freely soluble in methanol and
water, slightly soluble in chloroform and slightly
soluble in ethanol.
Deksketoprofen trametamol is a non-selective
nonsteroidal
anti-inflammatory
drug
of
the
arylpropionic acid group containing the active c-
enantiomer of racemic ketoprofen, an analgesic
characterized by a rapid onset of action and a relatively
short half-life. Trometamol salt ensures rapid
dissolution and absorption, which is especially
important in severe pain. The duration of pain relief is
4-6 hours, the mechanism of dual action from the
Volume 03 Issue 12-2023
8
American Journal Of Biomedical Science & Pharmaceutical Innovation
(ISSN
–
2771-2753)
VOLUME
03
ISSUE
12
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6-13
SJIF
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FACTOR
(2021:
5.
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(2022:
5.
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(2023:
6.534
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
central and peripheral side is of particular interest to
him, as a result of which dexketoprofen prevents the
increase of pain, as well as the formation of “Pain
memory” does. [2,6,7].
According to the regulatory document (NN 42 Uz-
8979-2018) and with the recommendation of
pharmacologists,
the
therapeutic
dose
of
deksketoprofen-trametamol
substance
was
determined to be equal to 36.9 mg.
Size 8 empty capsules were used for scientific
justification of capsule size.
For determination of encapsulable masses and
technological properties and quality indicators of
capsules, such as dispersion, fraction of fractions 0.2-
0.5 mm in size, dispersion density, angle of natural
deviation, disintegration and residual moisture Uz DF
Volume 1 and DF was performed according to the
methods defined in Edition XIV (RF). Tests were
performed five times and average values were
calculated. [5,9,10].
Research results and their discussion. First of all, it was
necessary to scientifically justify the size of the capsule.
For this, the volume occupied by deksketoprofen
trametamol substance based on the dispersion density
indicator is calculated.
The obtained results are presented in Table 1.
Table 1.
Results of choosing the size of the capsule that stored deksketoprofen trametamol
Capsule size
5
4
3
2
1
0
00
000
The average volume of the
capsule, sm3
0,13
0,21
0,30
0,37
0,5
0,68
0,95
1,37
The volume occupied by
the therapeutic dose of
deksketoprofen
trametamol substance, %
95%
45%
32%
26%
19%
14%
10%
7%
Empty volume, %
5%
55%
68%
74%
81%
86%
90%
93%
The results presented in Table 1 showed that the
therapeutic dose of deksketoprofen trametamol
substance is small, so the occupied volume is also
small. For this reason, it was determined that it is
appropriate to use 3-dimensional capsules in the
development of the capsule drug form.
When choosing the composition of the capsule
containing deksketoprofen trametamol, from auxiliary
substances that are widely used in the pharmaceutical
industry today: corn starch as a filler, microcrystalline
cellulose, NaKMS, maltose, isomalt, dextrose,
maltodextrin,
silicon
dioxide,
potato
starch,
Volume 03 Issue 12-2023
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American Journal Of Biomedical Science & Pharmaceutical Innovation
(ISSN
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VOLUME
03
ISSUE
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6-13
SJIF
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(2021:
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(2022:
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OCLC
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Publisher:
Oscar Publishing Services
Servi
magnesium stearate from antifriction agents, stearate,
talc, calcium stearate, purified water as a wetting
agent, alcohols of various concentrations were used,
and capsule masses were prepared by wet granulation
method.
When creating a capsule drug form on the basis of
deksketoprofen trametamol, methods presented in
the literature were used to study its technological
properties of compositions in volatility, volatility
density, natural deviation angle, fragmentation,
fraction content from 0.2 to 0.5 mm in size and residual
moisture.
In total, about 15 compositions were prepared, and
from them the bulk compositions with good mass
dressing and positive technological bearings are
presented in Table 2.
Table 2.
Components of recommendations and technological views for a capsule containing the substance deksketoprofen
trametamol
Compositions
Technological properties of encapsulated masses
scattering,
10
-3
kg/s
scattering
density,
kg/m
3
natural
deviation
angle,
degree
size
Percentage of
fractions 0.2-
0.5 mm , %
residual
moisture,
%
moment of
Decay
compound
-1
4.43±0,78
0,442±20,62 31,09±1,05
80,32±1,65
2,03±0,22
7,75±1,13
compound
-2
5,79±1,09
0,578±16,47 32,04±1,66
92,14±1,38
2,05±0,33
6,55±1,45
compound
-3
3,78±0,68
0,622±17,83 35,22±1,70
92,32±1,91
2,02±0,20
6,07±0,58
compound
-4
5,93 ±0,92
0,785±20,19 32,5±1,52
97,41±1,02
1,92±0,42
5,10±0.21
compound
-5
4,08±1,29
0,698±18,20 30,02±1,28
88,8±0,78
1,8±0,21
5.07±0,54
According to the data presented in the literature, the
volatility and scattering density of the encapsulated
mass depends on the percentage of fractions from 0.2
to 0.5 mm relative to the total amount, and it is
recommended that this figure is not 85% less. 1 in the
mixture obtained by composition, the amount of this
fraction was less than 85%, which was 80.32±1.65%. At
the same time 2, 3, 4 and 5 mixtures according to the
composition the fraction amount given above
92,14±1,38%, 92,32±1,91%, 97,41±1,02 and 88.8±0.78%.
The proof of the cited opinion was demonstrated in the
results of the determination of volatility: with the
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1121105677
Publisher:
Oscar Publishing Services
Servi
proportion of fractions of 0.2-0.5 mm greater than 85%,
the volatility was also higher, for example 4.43±0,78 10-
3 kg/s (1-composition), 5,93 ±0,92 10-3 kg/s (4-
composition), 4,08±1,29 10-3 kg/s (5-composition).
It was the scattering density of compositions 3, 4 and 5
that also showed high performance and, respectively
0,622±17,83 kg/m3, 0,785±20,19 kg/m3 va 0,698±18,20
kg/m3 was equal.
The angle of natural deviation was positive in all
analyzed compositions and this indicator was from
30.02±1.28 degrees to 32.5±1.52 degrees.
According to UzR DF and DF XIV edition (RF), the
disintegration of granules should not exceed 15
minutes. All tested compositions met the requirement
for this indicator and their disintegration time ranged
from 5.10±0.21 minutes to 7.75±1.13 minutes, i.e. did not
exceed the specified 15 minutes. At the same time,
residual moisture should not exceed 5%. All the
analyzed contents met the requirement and the
moisture content in them was 2,03±0,22%, 2,05±0,33%,
2,02±0,20%, It was 1.92±0.42% and 1.8±0.21%.
Taking into account the above, the most optimal mass
for the capsule was 2 and 4 compositions. But since the
scattering indicator is of great importance at the time
of filling the capsule, 4 ingredients with a high level of
this indicator were selected.
The obtained mass according to this composition was
prepared according to the following technology:
Taking into account the physico-chemical and
technological properties of the substances, it was
considered preferable to prepare the encapsulated
mass by wet granulation method. For this,
dexketoprofen, trometamol and maltose substances
were passed through a sieve with a hole diameter of
150 μm.Half the amount of cornstarch was added and
mixed until a uniform mass was formed. Purified water
was added by spraying until a moderately wet mass
was formed. The wet mass was passed through a sieve
with a diameter of 3000 μm and dried on a drying rack
at a temperature of 40-
500С until moderate moisture
remained.The dried mass was passed through a sieve
with a hole diameter of 1000 μm and mixed with the
rest of corn starch and a mixture of calcium
stearate.The resulting mass was placed in 3-
dimensional capsules of 100 mg.
A drawing of the technological process of obtaining
the capsule drug form of the deksketoprofen
trametamol substance is shown in Figure 1.
The quality indicators of finished capsules depend on
the technological indicators of the mass. At the same
time, the technological properties of the mass are
affected by the added auxiliary substances and the
technology of mass preparation. For this reason, the
technological properties of the encapsulable mass
were studied in the next research and compared and
studied with these properties of the substance. The
results obtained were presented in Table 3.
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Publisher:
Oscar Publishing Services
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Table 3.
Comparative study of Deksketoprofen trametamol substance and technical properties of capsular mass
Identified indicator
Unit of
measure
Deksketoprofen
substance
encapsulated mass
Fractional composition:
+1000mkm
-1000mkm +500mkm
-500mkm +250mkm
-250mkm +160 mkm
-160 mkm
%
2,04
19,97
50,42
20,25
7,32
1.6
20,82
51,49
21,31
4,78
scattering
10
-3
kg/s
0,511
5,93
scattering density
g/sm
3
0,39
0,785
Natural deviation angle
grade
62
32,5
Residual moisture
%
2,07
1,92
Based on the given results, the technological
properties of the encapsulable mass were more
positive than those indicators of the deksketoprofen
trametamol substance. In it, the smallest amount of
the substance (2.04%) corresponded to particles larger
than +1000 mkm and to the encapsulated mass (1.6%).
The main part of the substance -1000 mkm +500 mkm
(19,97%) composed of particles, it has a mass to be
encapsulated (20.82), particles -500 mkm +250 mkm
(50.42%) of the mass to be encapsulated (51,49) and -
250 mkm +160 mkm (20,25%) from (21.31%), substation
(7,32%) from (4.78%) to -160 mkm consisted of small
particles. This, in turn, shifted the dispersibility of the
encapsulated mass in a positive direction. This index
0,511*10-3 kg/s from increased to 5.93*10-3 kg/s.
Similarly the scattering density of ham increased
(0.39g/sm3 from up to 0,785 g/sm3). Deksketoprofen
trametamol substance had a negative result of the
angle of natural deviation (62,0 grade) and the
encapsulated mass showed a positive result (32.5
degrees). At the same time, it was proved that it has
residual moisture (2.07%) to (1.97%).
Scheme 1.
Technological process
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Oscar Publishing Services
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VR 1.1. Preparation of production rooms
VR 1.2. Preparation of technological equipment
VR 1.3. Training of production personnel
VR 1. Auxiliary works
VR 1.4. Preparation of raw
materials and packaging
materials
Losses
VR 1.5.
Grinding and
sorting of products
Losses
TR 1.1. Mixing, wet
granulation and drying
Losses
TR 1. Preparation of the
encapsulated mass
TR 1.2. Granulation
TR 2.1. Mass encapsulation
TR 2. Encapsulation
Loss
UMO 1.1. Capsule
packaging
UMO 1. Packing,
fitting and wrapping
UMO 1.2. Equipment
Finished product
TR 1.3. Massage
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Scheme 1. The technological process of obtaining a capsule
CONCLUSION
The composition of the capsule drug type was selected
and the technology was developed using the method
of auxiliary substances and wet granulation, which
were used in order to improve the negative
technological properties of the capsule in the creation
of the drug form on the basis of deksketoprofen
trametamol substance. The technological properties of
the substance and the encapsulated mass were
studied in a comparative way, and the selected content
was proven to be purposeful. This ensures that the
quality and shelf life of the removable capsules is on
demand.
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