American Journal Of Biomedical Science & Pharmaceutical Innovation
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VOLUME
Vol.05 Issue01 2025
PAGE NO.
20-25
10.37547/ajbspi/Volume05Issue02-06
Development of composition and technology of capsule
drug form extracted based on "cobalt-30 neo" substance
K.R Ramazonova
Institute of Pharmaceutical Education and Research
I.A Xodjaeva
Institute of Pharmaceutical Education and Research
Received:
17 December 2024;
Accepted:
19 January 2025;
Published:
21 February 2025
Abstract:
The fractional composition, dispersibility, bulk density, and residual moisture of the γ
-cyclodextrin
derivative of Cobalt-30, the "Cobalt-30 neo" substance, were determined according to the applicable regulations.
In developing the composition and technology of the capsules, the type and number of excipients were selected,
taking into account the technological properties of the mass. The composition and technology of the "Cobalt-30"
capsule were developed, and all these aspects were thoroughly studied in the article.
Keywords:
"Cobalt-30 Neo", dispersibility, bulk density, residual moisture, capsule drug form, excipients.
Introduction:
One of the urgent and important issues
of the modern pharmaceutical industry is to increase
the solubility of drugs, control the concentration and
rate of release of active substances from the drug form.
In order to solve this problem, various excipients are
used, as well as methods of incorporating drugs into
nano-sized materials are being used. In particular, the
cyclodextrin (CD) complex is increasingly attracting the
attention of scientists among many nanoscale agents.
Nowadays, cyclodextrin molecules are widely used by
scientists to create various drug forms. The use of
cyclodextrin and its derivatives makes it possible to
increase the stability of substances, reduce side effects,
active substances to easily pass through biological
barriers, and to achieve high effectiveness in small
doses. Today, a derivative of cyclodextrins with high
solubility and drug solubilizing activity - hydroxypropyl-
γ
-cyclodextrin (HP-
γ
-CD) is also widely used. In this
regard, Cobalt-30, a substance used in leukopoiesis and
hepatitis diseases, was synthesized as a supramolecular
complex compound with HP-
γ
-CD.
The purpose of the work
: to develop a capsule drug
form with optimal composition and scientific basis
based on the complex combination of Cobalt-30 with
HP-
γ
-CD.
Relevance of the topic
. Currently, among ready-to-use
drugs produced on an industrial scale, capsule drugs
take the leading place. The capsule form of the drug is
precisely dosed, has a rapid effect on the div and is
highly bio-efficient, and has the ability to prolong and
control the action of the active substance.
When choosing the composition and technology of
certain capsules, it is of great practical importance to
study the technological properties of the mass to be
placed inside the capsule. Also, the technological
properties of the substance "Cobalt-30 Neo" have a
significant impact on the choice of the type of drug, the
composition of excipients and the technology of
obtaining the drug. If the technological features of the
substance,
such
as
fractional
composition,
dispersibility, bulk density, and residual moisture, are
within the standard limits, the capsule fills evenly with
the substance, ensuring a consistent average capsule
weight. Moreover, the quantitative analysis meets the
required standards, ensuring the stability of the
capsule.
Experience part
. The experiments were based on
determining the physicochemical features and
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American Journal of Applied Science and Technology (ISSN: 2771-2745)
technological properties of the mass to be
encapsulated. The structural - mechanical properties of
the substance, specifically, the shape and size of the
particles, were determined according to the methods
given in the section 2.9.37 "Optical microscopy" of the
State Pharmacopoeia of the Republic of Uzbekistan.
The size and shape of the particles are one of the main
indicators that directly affect the technological
properties of the mass to be encapsulated.
Physicochemical
properties
of
particles
were
determined using an ADF U300P microscope with a
magnification of 10 to 600 times (Figure 1).
Figure 1. Magnified images of the substance "Cobalt-30 Neo" under an electron microscope
Looking at Figure 1, it can be seen that the substance
"Cobalt-30 Neo" is a polydisperse powder composed of
various particles, and it is mainly composed of plate-
shaped irregular particles of similar length and width.
At the next stage of the research, the technological
properties of the substance "Cobalt-30 Neo" were
studied, and the results of the fractional composition
analysis are presented in Table 1. The fractional
composition of the substance was determined
according to the method presented in the scientific
literature. To determine the fractional composition,
100 g of substance was placed in a set of sieves of
different diameters and then sieved. For this purpose,
100 g of mass was placed on the uppermost sieve and
a mechanical oscillatory motion was created for 5
minutes. Then the sieves were opened, the masses on
the sieve were weighed individually with an accuracy of
0.01g, and the obtained results were written in the
form of Table 1. The ones that remained on the sieve
were marked with (+), and the ones that passed
through the sieve were marked with (-). Fractional
composition was expressed in µm, %.
Table 1
Results of determining the fractional composition of the substance
"Cobalt-30 Neo" (n=5)
Fractional composition:
Units of measure
Obtained results
+1000
-1000 +500
-500 +355
-355 +250
-250 +180
µ km, %
54,75
25,7
11,7
3,71
2,35
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-180
1,79
Based on the obtained results, it can be concluded that
54.75% of the substance consists of particles larger
than +1000 µm. The proportion of -1000+500 µm
particles is 25.7%, while the -500+355 µm fraction
accounts for 11.7%. Additionally, -355+250 µm
particles make up 3.71%, -250+180 µm particles
represent 2.35%, and particles smaller than 180 µm
constitute 1.79%, as shown by the experimental
results. It is known that if the particles of the substance
and the mass to be encapsulated are of the same size
or the difference between their sizes is not large, the
amount of the active substance in the capsules filled
during the encapsulation process and the average
weight of the capsules will be the same and there will
be minimal deviations from it.
For the development of capsule drug forms, residual
moisture, dispersibility and bulk density of the
substance "Cobalt-30 Neo" were determined. The
results are presented in Table 2.
Table 2
Results of determination of technological properties of "Cobalt-30 Neo" substance (n=5)
Examined parameters
Units of measure
Obtained results
Dispersibility
g/s
3,4
Bulk density
kg/m
3
450
Natural deviation angle
degree
43
Residual moisture
%
4.45
According to the results of determining the
physicochemical features and technological properties
of the substance "Cobalt-30 Neo", it is necessary to
improve the fractional composition, dispersibility and
bulk densities. Various excipients were used for this
purpose, which are widely employed in the
pharmaceutical industry today. When choosing the
composition of the "Cobalt-30 Neo" capsule, corn
starch and microcrystalline cellulose were used as
fillers, sodium croscarmellose and sodium starch
glycolate as lubricants and dissolution enhancers, while
calcium stearate and magnesium stearate were used as
anti-friction agents. Taking into account the humidity of
the substance, it was first dried at 60⁰C for 1 hour and
then ground in a mill. 6 different compositions were
prepared with ground substance and various excipients
approved for use in medical practice (Table 3).
Table 3
Suggested compositions for "Cobalt-30 Neo" capsules
№
The substances taken for the
capsule mass, mg
Compositions, mg
1
2
3
4
5
6
Substance, mg
1.
"
Cobalt-30 Neo
"
81.7
81.7
81.7
81.7
81.7
81.7
Excipients, mg
2.
Magnesium stearate
2.5
2.5
2.5
3.
Calcium stearate
2.5
2.5
2.5
4.
Sodium croscarmellose
7.5
7.5
7.5
5.
Corn starch
158.3
158.3
158.3
6.
Sodium starch glycolate
7.5
7.5
7.5
7.
Microcrystalline cellulose
158.3
158.3
158.3
8.
The mass quantity for per capsule
250±10 250±10
250±10
250±10
250±10
250±10
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American Journal of Applied Science and Technology (ISSN: 2771-2745)
The technological properties of the prepared
compositions were determined according to the above
methods, and the obtained results are presented in
Table 4.
Table 4
The results of determining the technological parameters of the mass contained in the “Cobalt-30 Neo”
capsule
Examined parameters
Obtained results
Т-1
Т-2
Т-3
Т-4
Т-5
Т-6
Fractional composition, µm,
%:
+1000
-1000 +500
-500 +355
-355 +250
-250 +180
-180
2,6
9,4
64.09
18,35
4,3
1,26
2,34
9.1
65,22
17,5
4,6
1,24
2,1
9.8
67.73
15,8
3,4
1,17
2,8
9.4
65,11
17,3
4,2
1,19
2,2
9,8
63,48
18,7
4.54
1,28
2.95
9,51
64,08
18,1
4.11
1,25
Dispersibility, g/s
3,85
3,91
4,5
4,28
3,95
4,19
Bulk density, kg/m
3
502
512
569
525
528
523
Natural deviation angle, degree
43
45
35
42
40
37
Residual moisture, %
4,14
4,16
4,07
4,11
4,15
4,1
Disintegration time, min
13,33
13,33
9,24
10,3
11,33
9,55
From the results presented in Table 4, it can be seen
that all compositions have different technological
properties. The bulk density was 502-569 kg/m3, the
natural deviation angle was 35-45 degrees. The residual
moisture index in the mass to be encapsulated did not
exceed 5% in all compositions and was found to be
significantly improved compared to the initial
substance and was in the range of 4.07-4.16%.
However, the dispersibility of the prepared masses was
relatively low in the 1,2,5-contents, and the samples
containing corn starch were 3.85 g/s, 3.91 g/s, and 3.95
g/s, respectively. A mass with low dispersibility
increases the likelihood of sticking to the hopper of the
encapsulating machine.
The disintegration time of the capsules was determined
according to the method given in State Pharmacopoeia
of the Republic of Uzbekistan and did not exceed 20
minutes, as required by the pharmacopoeia.
Based on the above results, the technological
properties of the studied compositions were analyzed.
The number of excipients selected for composition №
3 demonstrated the most optimal indicators, including
dispersibility, natural deviation angle, fractional
composition, and residual moisture.
To prove the scientific justification of the selected
composition for the "Cobalt-30 Neo" capsule and to
preliminarily assess its compliance with ND
requirements, a comparative study of the technological
properties of the "Cobalt-30 Neo" substance and the
selected composition was conducted. The results are
recorded in Table 5.
Table 5
Comparative study of the technological properties of the substance “Cobalt-30 Neo” and the selected
composition
Examined parameters
Units of measure
Obtained results
“Cobalt-30 Neo”
substance
Selected
composition
(№3)
Fractional composition
+1000
-1000 +500
-500 +355
-355 +250
µm, %
54,75
25,7
11,7
3,71
2,1
9.8
67.73
15,8
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-250 +180
-180
2,35
1,79
3,4
1,17
Dispersibility
g/s
3,4
4,5
Bulk density
kg/m
3
450
569
Natural deviation angle
degree
43
35
Residual moisture
%
4.45
4,07
Based on the results, it was determined that the
fractional composition of the substance "Cobalt-30
Neo" was 11.7% of 0.355-0.5 mm particles, and the
fractional composition of the selected capsule mass
was 67.73%. This shows that the result is shifted in a
positive direction, leading to an improvement in the
dispersibility of the mass and the possibility of
obtaining a high-quality capsule increases. It was
proved that the dispersibility of the mass to be
encapsulated changed from 3.4 g/s to 4.5 g/s, the bulk
density from 450 g/ cm3 to 569 g/ cm3, and the residual
moisture from 4.45% to 4.07%.
Due to the correct selection of excipients in the
selection of the composition of the "Cobalt-30 Neo"
capsule, it was scientifically proven that the residual
moisture of the mass decreased, its dispersibility
improved and other technological indicators changed
in a positive direction. The selected composition was
recommended
for
further
research
on
the
development of capsule technology.
Thus, the composition of the drug "Cobalt-30 Neo" for
1 capsule was selected:
"Cobalt-30 Neo" 81.7mg
Sodium starch glycolate 7.5mg
Magnesium stearate 2.5mg
Microcrystalline cellulose 158.3mg
The average mass is 250mg
Technology
: To prepare the capsule mass, residual
moisture in "Cobalt-30 Neo" was dried to the optimum
level at a temperature of 60ºС, ground and sieved using
a 0.5 µm sieve. The excipients listed above were also
sieved using a 0.5 µm sieve and thoroughly mixed with
the substance. Capsules were filled by direct
encapsulation method in UXF-300 type mechanical
encapsulation equipment. The technological scheme of
obtaining "Cobalt-30 Neo" capsules is presented in
figure 2.
When filling the "Cobalt-30 Neo" capsule mass into
hard gelatin capsules, № 2 gelatin capsules were used.
The description of the technological process is
presented in Figure 2.
It is known that the direct encapsulation method of the
mass to be encapsulated without granulation is
practically economical and has the following
advantages: it does not require additional equipment
(granulator, mixer), reduces energy consumption, and
increases work efficiency. The composition of the
capsule offered on the basis of "Cobalt-30 Neo" shows
good technological properties and allows direct filling
of the capsule. The proposed capsule composition
based on "Cobalt-30 Neo" exhibits good technological
properties, allowing for direct capsule filling. In the
development of the above technology, the shape of the
powder particles and losses during grinding were taken
into account. The quality parameters of the hard № 2
dark yellow gelatin capsules obtained according to
formulation 3 were determined. The results are
presented in Table 6.
Table 6
Results of evaluation of the quality of "Cobalt-30 Neo" capsules
External
parameters
Average weight and
its deviation
g, %
Solubility,
%
(not
less
than
75%)
Disintegration
,
minutes
(not less than
20 minutes)
Quantitative
analysis,
Cobalt-30 mg
(13,5-16,5 mg)
(±10%)
Dark yellow hard
gelatin capsules
№ 2
-7,35%; +9.8%
90%
9,24 min
15.3 mg
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American Journal of Applied Science and Technology (ISSN: 2771-2745)
The obtained capsules complied with the requirements
specified in State Pharmacopoeia of the Republic of
Uzbekistan in terms of appearance, deviation from
average weight and dissolution time.
CONCLUSION
According to the results of the experiment, by studying
the technological properties of the "Cobalt-30 neo"
capsule, an alternative composition suitable for the
preparation of the capsule medicine was selected and
its technology was developed.
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