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ARTICLE INFO
DEVELOPMENT OF DISSOLVATION TEST FOR "HEPASILIMARIN" CAPSULES Kayumov F.S. Tukhtaev H.R. Akbarov N. Tashkent Pharmaceutical Institute E-mail: [email protected] https://doi.org/10.5281/zenodo.14202190
ABSTRACT
Received: 17th November 2024 Accepted: 21th November 2024 Online: 22th November 2024
KEYWORDS "HEPASILIMARIN" capsule, "solubility", "A ylanma kajava" device, "Dissolution" test, flavolignan.
In order to study its solubility in the gastrointestinal tract in the production environment of "HEPASILIMARIN" capsules, its dissolution test was carefully studied and alternative conditions were selected. Taking into account the importance of using the "in vitro" method, which is the most suitable method in laboratory conditions, practical work was carried out in this method to determine the dissolution test. In performing the experimental part, the equipment of the rotating cajava was used, as specified in the 1st volume of the Pharmacopoeia of the Republic. . Using the equipment, the rate of release of biologically active substances with flavonoid properties contained in the mass of "Hepasilimarin" capsule into the solvent medium, as well as the factor influencing the process of fruitless dissolution, the pH numerical index, were studied. Purified water (pH=5.8), 0.1 molar HCL hydrochloric acid (pH=1.3), sodium bicarbonate NaHCO3 as a solvent medium 0.1 molar (pH=8) solution of 0.01 molar sodium tetraborate Na 2 B 4 O 7 (pH=9.2) solutions were used. Take it went studies result "in vitro" method is correct for "HEPASILIMARIN" capsules coming The "Reaching" test was developed.
The entire pharmaceutical sector is in urgent need of both innovative technological solutions and fundamental scientific work that enables the production of highly engineered drugs. Commercial production of complex drug delivery systems is difficult using existing technologies [1]. Drug delivery systems often involve biopharmaceutical studies in solution form, which requires the investigation of changes in their physical and chemical properties and biological activity. Scientific study of different dosage forms of drugs, as well as physical, physico-chemical properties of bioactive and auxiliary substances in drugs with the same dosage, and their effect on pharmacotherapeutic properties [2].
Today, one of the forms of the drug? Determining the dissolution rate and environment of capsules is one of the important factors of production in enterprise conditions. It is similar to conducting such experiments using the "in vitro" method in pharmaceutical practice results
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gives Using this method, biologically active substances in the form of a solid drug capsule are transferred to a pre-planned solvent medium, and this condition allows the capsules to be absorbed in the gastrointestinal tract. In vitro, when the BFMs contained in the capsule are transferred to an environment where a solvent is present, this allows the BFMs to be absorbed into the body in the gastrointestinal tract . Medicine of forms eruvcjan tests mainly in "in vitro" and "in vivo" methods done is increased but basically laboratory under the conditions of the "in vivo" method use much comfortable and efficient only no more work perform the procedure is also easy [3,4].
Today, there are several methods that determine the dissolution rate of solid drug forms. Usually they differ from each other in the size of the solvent medium, its mobility or immobility, pH of the solvent medium. Dissolution of a tablet or capsule is the amount of active substance that has changed from a solid drug type to a solution within a certain time. In order to determine the dissolution of tablets or capsules, the device "Rotary Kajava" presented in DF XI is used [2,6].
The main reasons for the widespread use of the "circulating kajava" method are the high correlation of the obtained research results with the results of "in vivo" experiments in many cases, the simplicity of the method, the ease of implementation and the low cost [6].
In the dissolution test for the capsule dosage form according to DF XI, the release of the bioactive substance is affected by temperature, rotation speed of the device, volume and nature of the dissolution medium [5].
"HEPASILIMARIN" capsules with choleretic properties in "in vitro" experiments was determined as the goal of scientific research .
Experiment part.
Research methods and tasks.
a positive effect on liver function and [oleritic effect, were selected as the object of scientific research . A mixture of dry extracts of "Hepasilimarin", microcrystalline cellulose, potato starch, calcium stearate is included in the composition of the capsule , and its average mass is equal to -0.5 g.
The experiments were carried out based on the requirements of the "Solubility" test for solid drug forms" in the DF I edition of the Republic of Uzbekistan [5,7]. In order to determine the bioefficacy of "HEPASILIMARIN" capsules, a dissolution test in "in vitro" conditions was introduced from the "Erweka DT" type rotating cajava device.
The conducted experiments were carried out in the following order: by placing one capsule of "Hepasilimarin" in a rotating cajava device, the release of BFMs contained in the capsule, the influence of the rotation speed of the cajava, the "Dissolution" test of "HEPASILIMARIN" capsules, 4 types of rotating cajava, i.e., 50, 100, 150 and It was carried out at a rotation speed of 200 rpm (experiments were repeated 5 times).
Research results and their discussion.
"HEPASILIMARIN" capsules, the experiments were carried out in the following order: by placing one "HEPASILIMARIN" capsule in a rotating cajava device, to study the effect of the release of BFMs contained in the capsule and the rate of rotation of the cajava, purified water (pH=5.8), 0 , 1 molar hydrochloric acid (pH=1.3), 0.1 molar (pH=8) solution of sodium bicarbonate, sodium tetraborate (pH = 9.2) solutions were poured into containers filled with
é
Ws,
The average amount of biological substances in
Under study factors the Hepacilymarin capsule,%
Flavonoids Flavolignans Flavonoids
Routine Silymarin Luteolin
Cleaned up 1 0 48 % 52 % 51 %
water (p H 2 0 72 % 74 % 83 %
=5.8) CD 30 87 % 85 % 8 3 %
■M g 0.1 molar HCl 3 g 10 47% 46 % 48 %
CD (pH=1.2)
S S 20 68% 6 7 % 79 %
o CD a OD S '■w
> a CD >> 30 8 3 % 82 % 78%
0.1 molar 10 7 % 3 % 8 %
■M <A Si CD T3 a D NaHCO3(pH =7.8) ■M
0 -fi <A 2 0 19 % 12 % 11 %
b 30 24 % 22 % 17 %
0.01 mol/l Na 2 H 10 0.5% 0.1% 2.6 %
B 4 O 7 (p H= 20 0.8% 0.3 % 3.9 %
9.18)
30 1.9% 0.6% 7.7 %
During the experiment, the temperature was 37 0 C±1 0 C. Each medium containing HEPASILIMARIN capsules was sampled every 5 minutes and the amount of exposed BFM was measured. The release of BFM when using purified water in a rotating cajava as a solvent showed higher release compared to other solvent media. After that, slightly lower results were obtained when 0.1 M hydrochloric acid solution was used as a medium compared to purified water. The parameters obtained in the medium of solutions containing 0.1 m sodium hydroxide and 0.1 m sodium tetraborate were shown to be unsatisfactory [5-7 ].
Taking into account the results of the research, it was found appropriate to use purified water as a solvent medium. The obtained experimental results are given in Table 1. According to the obtained results, the results of the assessment of the influence of the pH environment of the solvent on the rate of release of BFMs from "GEPASILIMARIN" capsules into the solvent environment are given, was 80%, 86%. In further studies, the influence of complete separation of BFMs contained in the capsule, which is considered as the second indicator, on the rotation speed of the rotating cajava, experiments were carried out for every 50, 100, 150 and 200 rpm. The results of the experiment are shown in Table 2.
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Table 2
Results of the study of the effect of cajava speed on the complete release of biologically active substances included in the capsule "HEPASILIMARIN"
Under study factors "Hepasilymarin" capsule,%
Flavonoids Routine Flavolignans Silymarin Flavonoids Luteolin
Rotational speed, rpm 50 Time , minutes 10 29 % 48 % 52 %
20 38 % 56 % 58 %
30 42 % 65 % 67 %
100 10 47 % 53 % 58 %
20 65 % 68% 72 %
30 84 % 87 % 89 %
150 10 54 % 59 % 64 %
20 72 % 66 % 79 %
30 84 % 83 % 8 8 %
200 10 58 % 5 3 % 67 %
2 0 7 4 % 6 9 % 81 %
30 82 % 8 4 % 87%
"HEPASILIMARIN" capsule to the existing solvent of BFM was shown in the maximum 30 minutes when the number of revolutions per minute was 150 , and the percentage of released substances was found to be 88%.
When the number of revolutions in the device was increased to 100 per minute, the percentage of release of BFMs contained in the "GEPASILIMARIN" capsule into the solvent medium was 84%, 87% and 89%. After that, when the number of revolutions was reached to 150 and 200, the amount of released BFMs was 88% and 87%, respectively. When the number of rotations was increased to 100 per minute, the yield of release of biological active compounds from "HEPASILIMARIN" capsules showed its highest intensity at 30 minutes.
Summary. It was shown that more than 75% of the flavanoid was released into the dissolution medium within 45 minutes at the speed of the rotating cajava. According to the results of the release rate of BFMs when using purified water, 0.1 molar HCl, 0.1 molar sodium bicarbonate, and 0.01 molar sodium tetraborate solutions in vitro, purified water was selected as the solvent medium in the dissolution test. In this case, taking 1000 ml of purified water as a medium was also considered to be effective in the experiments.
As a result of rotating the rotary device at different levels per minute, the percentage of release of BACs contained in the "HEPASILIMARIN" capsule into the solvent medium was 89%.
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