CC BY
16
Section 1. Medicine
Hudojberdiev Olloqul Isoqovich, pro-rector, Tashkent pharmaceutical institute, Hadzhieva Umida Abdulxaevna, senior research associate, Uzbek chemico-pharmaceutical scientific and research institute,
Madzhitova Dildora Umarkhanovna, junior research associate, Uzbek chemico-pharmaceutical scientific and research institute,
Azizov Umarkhon Mukhtorovich, deputy director, professor. Uzbek chemico-pharmaceutical scientific and research institute,
E-mail: [email protected]
WORKING OUT OF THE METHODS OF QUALITY CONTROL AND STANDARDIZATION OF THE DIURETIC PREPARATION OF "EKUSTIM" CAPSULES
Abstract: "Ekustim" capsules have been standardized according to the requirements VFM on such indicators as the description, authenticity, solubility, average weight, desintegration ability, microbiological cleanliness and quantitative definition. On the basis of the results of conducted researches the project of worldwide officinal article is made.
Keywords: a dry extract and capsules of "Ekustim", quality monitoring methods, standardization, average weight, desintegration ability, dissolution, microbiological cleanliness, quantitative definition and metrological characteristics.
Synthetic medical products which applied now as diuretics and sell in chemist's network of the ROU basically are delivered on import and are expensive.
Necessity of working out new diuretic preparations are caused by a great demand of public health services for the cheap domestic medical products which have no side effects.
In this respect phytogenesis preparations are more preferable, as they affect more softly, they are better tolerance, in most cases do not cause an allergy and may be applied long without side effects. How-
ever, an essential lack of these preparations is low concentration ofyaaycemTn beginning in those recommended medicinal forms (teas, infusions, broths) and accordingly, small efficiency in clinical practice. In this connection obtain of dry extracts from plants with allocation of the basic effecting substances allows to remove the specified lacks. Reception of dry extracts from medicinal vegetative raw materials provides the big profitability and rationality of its use as the maximum output of dietary supplements in this case is reached, pharmacotherapeutic efficiency of
preparations raises at the expense of possibility of its dispensing.
Earlier we had been developed technology of reception of a dry extract "Ekustim" (Urostim) consisting of a mix of dry extracts of the following 8 herbs: grasses of alhagi false, grasses of erva woolly, grasses of a field horsetail, grasses of ground burnut, florets of silvery yarrow, seeds of cucumbers, columns with corn silk and naked licorice, for getting capsular medicinal form [1-2].
Now we developed the technology of getting of "Ekustim" capsules in the form of a capsule by 0.35 gram, in following structure:
Dry extract "Ekustim" - 0.350 g;
Microcrystalline cellulose - 0.095 g;
calcium stearate_- 0.005 g;
Average weight - 0.450 g.
Research objective. The purpose of the present research is working out of a quality monitoring methods and standardization of "Ekustim" capsules.
Experimental part. An investigated preparation standardized according to the requirements of GF XI on the following indicators: description, authenticity, average weight, desintegration time, dissolution, microbiological cleanliness, quantitative definition. Capsules of "Ekustim" represent the firm of gelatinous capsules in the size "0" containing deep brown granule with a specific smell.
Authenticity establishment was conducted on qualitative reactions to the basic acting substances: the sum of flavonoidsoB and hardening agents.
450 mg of a powder of contents of capsules of a preparation are placed into a measured flask by volume of 25 ml, add 10 ml of water, mix and lead the volume by purified water to a mark and filtered through the paper filter of G0ST(l20226-76) (solution A). To 2 ml of the received filtrate add 5-6 drops of 5% spirit solution of iron (Ill)-chloride; a green coloring occur (tannins).
450 mg of a powder of contents of capsules of a preparation are boiled during 5 minutes with 20 ml of water and is filtered. To 5 ml of a filtrate add 3 ml
of1% spirit solution of aluminum chloride; flavovi-rent colouring occur (flavonoids).
Average weight and deviation from average weight of contents of capsules. The average weight of contents of one capsule should be from 405 mg to 495 mg. The deviation from average weight of separate capsules contents should be ± 10% at 18 capsules and ± 25,0% (but no more) at 2 capsules. During the conducted tests it is established, that all capsules meet these requirements.
Definition of desintegration time of capsules were conducted by a technique described in GF XI edit [2, P. 24]. Thus all tested capsules withstand general requirements of GF XI and of have completely broken up within 15 minutes.
One of the basic indicators of quality of capsulat-ed medical products is the test for dissolution which simulates destiny of a preparation in a gastroenteric path.
Definition of solubility of a preparation was conducted according to the requirements of GF XI, edit. [2, P. 159].
By one capsule are placed to each of 6 baskets, a basket was immersed in the vessel containing 500 ml of purified water, with temperature (37 ± 1)° C and switch on the device. After 45 mines pass select test from the vessel centre and filter through the paper filter "Dark blue tape". To 250 ml of a filtrate add 25 ml of anilic sulpho-acids and titrated with 0,02 mol/l solution of KMp04 up to golden-yellow coloring.
Control experience is conducted in parallel. 500 ml of water, 25 ml of anilic sulpho-acids. 1 ml 0.02 pier/l of solution of KMn04 corresponds to 0.004157 g of tannins in recalculation to tannin.
The content of tannins (X), in% conversion is calculated as per the following formula: x_(V - V1 )• 500 • 4.15 • K-100 _ 17.5 • 250
Where:
V - Volume of a solution of potassium permanganate (0,02 mol/l), spent to titration of the examined solution, ml;
V - Volume of a solution of potassium permanganate (0.02 mol/l), spent to titration in control experiment, ml;
4.15 - the quantity of tannins corresponding to 1.0 ml of 0.02 mol/l of KMn04 solution;
17.5 - the declared quantity of tannins in one capsule, mg;
K - correction factor.
The quantity which has passed to the medium of dissolution of tannins should be not less than 75%.
Loss in weight drying was defined on GF XI. Nearby 1.0 g (exact weighed portion) of granules of capsules contents was dried at temperature 100105 °C to constant weight. Loss in weight makes 3-5%.
Microbiological cleanliness of preparation was estimated under the requirements of GF XI, edit. [2, P. 193] "Methods of microbiological control of medical products" and amendments № 2 dated 25.09.20056 a category 3B at these experiments conducted in five series the satisfactory results corresponding to specified requirements were received.
Quantitative definition of sum of flavonoids were conducted by the technique described in XI, edit [2, P. 324].
450 mg (exact weighed portion) of the powder of contents of capsules are placed in a flask with capacity of 100 ml, add 50 ml of 50% of a solution of hot ethyl spirit and mixed. After cooling at a room temperature, solution volume lead up by the same solvent to the mark and filter through the paper filter (solution A). 3.0 ml of a solution place in a flask by capacity of 25 ml, add 3.0 ml of 2% chloride aluminum, 1 drop of the diluted acetic acid and lead up volume of a solution of 96% ethyl spirit to the mark. A solution is mixed and placed in a dark place. After 40 minutes pass, optical density of the received solution is measure on spectophotometer at length of a wave of400 nanometers, in a ditch with thickness of a layer of10 mm. The solution prepared in the same way, but without adding of a solution of chloride aluminum is used as a comparison solution.
Optical density of a rutin solution of the standard sample (SS), prepared similarly to the tested solution is measured in parallel.
The sum of flavonoids content (X), in mg in one capsule, in equivalent to rutin is calculated as per the formula:
X _ D1 • a0-100 • 25-1-b-1000 _ D1 • a0 • b • 333.3 D0 • a1 • 3 400• 25 D0 • a1 ,
Where:
D1 - optical density of a solution oftested sample;
D0 - optical density of a solution of the standard sample of rutin;
a1 - Weight of weighed portion of tested sample, in mg;
a0 - Weight of weighed portion of the standard sample of rutin, in mg;
b - Average weight of contents of one capsule, in mg.
Note. Preparation of a solution of the standard sample of rutin. About 0.05 g (exact weighed portion) of rutin (FC42 Uz-0137-2007), preliminary dried up at temperature (130-135° C) during 3 hours is placed in a measured flask with capacity of 100 ml and dissolved in 85 ml of 96% of ethyl spirit at heating on a water bath. After cooling at a room temperature solution volume lead up by the same solvent to a mark and mixed. 1.0 ml of the received solution is placed in a measured flask with capacity of 25 ml and further make the same way, at preparation of the tested solution beginning from words "... add 3.0 ml of a solution of 2% aluminum chloride ..." to "... without adding a solution of aluminum chloride. A period of storage of a solution is1 month.
Preparation of a solution of 2% aluminum chloride.
2.0 g of aluminium chloride (GOST 3759-75) is placed in a measured flask by a capacity of 100 ml, dissolved in 96% of ethyl spirit and lead up solution volume by the same solvent to the mark. A period of storage of a reactant is 3 months.
Results of the analysis are given in table 1.
Table 1.- Metrological characteristics of a technique of quantitative definition of the sum ^a flavonoids of "Ekustim" capsules
Content of a sum of flavonoids,% metrological characteristics
5.8 f = 4; X = 5.88; S2 = 0.007; S = 0.0837
5.9 S = 0.0374
6.0 T (95%.4) = 2.78
5.8 AX = 0.2326; AX = 0.1040; £ = 3.95%
5.9 cp £ = 1.77% —cP-
Apparently from (table 1), Content of flavonoids fluctuates in one capsule within 5.8-6.0 mg. Therefore not less than 4.5 mg was fixed as the norm of the content of the sum of flavonoids in one capsule.
Content of tannins. 450 mg (exact weighed portion) of a preparation is placed into a measured flask by capacity of250 ml, add 100 ml of water, dissolved, lead up to a mark by water, mix. 25 ml of the received solution is transferred to a conic flask by capacity of 1 liter, add 750 ml of water, 25 ml of a solution of anilic sulpho-acid and titrate at mixing with 0.02 mol/l solution of KMn04 up to golden-yellow color.
Control experiment are held in parallel. 750 ml of water, 25 ml of anilic sulpho-acid.
The content of tannins (X), in% conversion are calculated as per the formula:
X =
(V - V )• 0.004157 • 250-100
a • 25
Where: V - Volume of a solution of potassium hypermanganate (0,02 pier/l), spent for titration of the tested solution, ml;
V - Volume of a solution of potassium hypermanganate (0.02 pier/l), spent for titration in control experiment, ml;
a - mass of weighed portion of a preparation in gram;
0.004157 - content of tannins corresponding to 1 ml 0.02 mol/l of KMn04 solution, g.
Apparently from (table 2), the content of tannins in one capsule fluctuates within 6.3-6.5%, Therefore the norm of the content of tannins has been fixed not less than 5%.
Table 2.- Metrological characteristics of a technique of quantitative definition of the sum ^a flavonoids of "Ekustim" capsules
Content of sum of tannic,% metrological characteristics
6.3 f = 4; xp = 6.38; S2 = 0.007; S = 0.0837
6.5 S = 0.03744
6.4 T (95%.4) = 2.78
6.4 AX = 0.2326; AX = 0.1040; £ = 3.64% CP '
6.3 £ = 1.63%
Table 3.- Numerical indicators of "Ekustim" capsules
Name of index Norm for "Ekustim" capsules
1 2
Description Hard gelatin capsule of size 0. Contents of capsule granule deep brown with characteristic smell.
Identity Reaction with 1% spirit solution of aluminum of chloride there is a flavovirent coloring (flavonoids). Reaction with 5% spirit solution of iron (Ill)-chloride; there is a green coloring (tannins)
1 2
average weight and deviation from average mass of capsules content. Should be from 405mg to 495 mg
desintegration time No more than 20 minutes
solubilization No more than 75%
content flavonoids in equivalent to rutin Not less than 4.5 mg
content of hardening agent Not less than 5%
Proceeding from results of the analysis of "Ekustim" capsules we establish the norms of numerical indicators regulating its quality (tab. 3).
Expiration date of "Ekustim" capsules is studied according to OST 42-2-70 in natural conditions
and it is established, that it makes more than 2 years. On the basis of the given experiments, the project of time of officinal articles on "Ekustim" capsules is developed.
References:
1. Azizov U. M., Hadzhieva U. A., Madzhitova D. U., Hudojberdiev O. I. / Standardization of a dry extract "Urostim" // Pharmaceutical magazine.- Tashkent,- 2017.- No. 2.- P. 51-54.
2. Azizov U. M., Hadzhieva U. A., Madzhitova D. U., Hudojberdiev O. I. / Creation and working out of the technology of "Urostim" diuretic agent on the basis of a combination of local herbs // Pharmaceutical magazine.- 2017.- No. 3.- P. 98-102.
