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DEVELOPMENT OF TECHNOLOGY OF THE DRAGEE ON THE BASIS OF THE DRY EXTRACT RECEIVED FROM ROOTS AND RHIZOMES OF THE GERANIUM COLLINIUM AND STUDYING OF ACUTE TOXICITY OF PREPARATIONS
Sharipova Irodahon Shavkatovna, Vazirova Muhaye, Aliev Habibullo Ubaydullaevich, Tashkent pharmaceutical institute, Technology of Medicinal Forms
E-mail: fattahov_bob@mail. ru
Abstract. It is for the first time developed structure and technology of a dragee on the basis of dry extract of a Geranium collinium, containing ascorbic acid and phytin with application of a drageeing copper and dragees are called "Gerasfit" and "Gerask". On the basis of the made experiments limits of rationing of a dragee are defined: appearance, authenticity, disintegration, average weight, uniformity of dispensing, dissolution, microbiological purity, quantitative definition of active ingredients acute toxicity of preparations is also studied.
Keywords: Geranium collinium, dry extract, tannins, ascorbic acid, phytin, dragee, quantitative definition, acute toxicity, strengthens the capillaries.
Introduction
Geranium collinium (Geranium collinum Steph.) in traditional medicine broth from underground bodies of a plant is used. The local population is used at gastric diseases, as styptic during the postnatal period, at a blood spitting, and also as knitting and fixing. According to literary data broth from underground bodies and infusion of a grass of a Geranium collinium, possess the expressed anti-inflammatory and antihypoxemic activity and antioxidant action [1]. The studied look - a Geranium collinium, represents a perennial grassy plant with well-developed root system. In Uzbekistan skilled plantations are put. All parts of a plant contain high-quality tanida (in elevated parts-11 - 23%, in underground more - 50%). According to literary data, the Geranium collinium contains the following biologically active agents in roots and rhizomes: carbohydrates; monosaccharides; water-soluble polysaccharides; pectinaceous substances; gemitsellyuloza; amino acids; vitamins - ascorbic acid; organic acids; flavonoids; fenolkarbon acids and tannins [2].
For preparation of a dragee dry extract is received from roots and rhizomes of a Geranium collinium by a percolation method, alcohol ethyl is used 40%. The dry
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extract received from roots and rhizomes of a Geranium collinium, represents powder light-brown color, with a specific smell, strongly knitting taste, we will easily dissolve in water and alcohol, humidity of extract-4,9%, the content of heavy metals doesn't exceed-0,01%, an exit of dry extract of 30-31% in relation to raw materials, tannins not less-51 than a % [3].
The aim of the research. Creation of a medicinal form - a dragee on the basis of dry extract from a Geranium collinium, containing ascorbic acid and phytin, having applied a drageeing copper, having carried out the qualitative and quantitative analysis of biologically active agents and studying of acute toxicity of a dragee.
Experimental part. After detailed studying medicinal and excipients we stopped on the following structures of a dragee.
The first composition (Gerasfit) in g The second composition (Gerask) in g.
Composition per one dragee Dry extract of geranium collinium 0,1000 Composition per one dragee Dry extract of geranium collinium 0,1000
Ascorbic acid Phytin 0,05 0,1000 Ascorbic acid 0,05
Excipients: Sugar Beeswax Sunflower oil Purified Water - necessary amount to obtain dragées weighing - 0,5g 0,2488 0,0006 0,0006 Excipients: Sugar Beeswax Sunflower oil Purified Water - necessary amount to obtain dragées weighing - 0,5g 0,3488 0,0006 0,0006
Technological process is in detail given in the previous messages [4]. The prepared dragees we called conditionally - a dragee of "Gerasfit" and "Gerask".
Studying of quality indicators of ready dragees. To ready dragees a number of requirements for SPh (State Pharmacopeia) XI are shown: appearance, authenticity, disintegration, average weight and a deviation from average weight test of uniformity of dispensing, dissolution, microbiological purity and quantitative definition of biologically active agents [5].
Appearance. A dragees of "Gerasfit" and "Gerask" of a round form, light-brown color, smooth, on a cut uniform.
Authenticity. For determination of authenticity of a dragee in view of that in extract the high content of tannins and their high pharmacological activity, a number of high-quality reactions to tannins, and also on ascorbic acid and phytin are carried out. Authenticity of tannins in a dragee of "Gerasfit" and "Gerask" was established by the following reactions: with 1% FeCl3 solution, 1% solution of gelatin, 1% solution of ammonium of chloride, 1% hydrochloride quinine solution - was observed greenish
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brown coloring, loss of a curdled deposit, light-yellow coloring and loss of an amorphous deposit. On ascorbic acid - with 1% silver nitrate solution with solution 2,6 -dikhlorfenolindofenolyaty sodium observed loss of metal silver, there was a solution decolouration. On phytin - reaction with solution of nitrate of ammonium and molybdate of ammonium - white rainfall dropped out. All done reactions confirmed existence in a dragee of tannins, ascorbic acid and phytin.
Disintegration. Determination of disintegration of a dragee of "Gerasfit"and "Gerask" carried out by the technique described in The State pharmacopoeia XI. Where in the studied dragees broke up from 5 to 7 min.
The average weight and deviation from average weight. The deviation in the mass of separate dragees has to differ in method of building from average weight no more than ± 7,5%, the deviation from the average mass of a dragee of "Gerasfit" made ±2,4%, an admissible limit of 0,4634±0,5366 g, average mass of a dragee - 0,4880 g, in a dragee "Gerask" the deviation made ±2,2%, an admissible limit of 0,4633±0,5367 g the average mass of a dragee - 0,4894 g.
Uniformity of dispensing. And 'Gerask" contains ascorbic acid in number of 0,05 g in the prepared dragees of "Gerasfit", according to requirements of GF XI for a dragee carrying out researches on uniformity of dispensing of a preparation is obligatory. The quantitative content of ascorbic acid to a dragee of "Gerasfit" and "Gerask" was carried out separately by titration of 0,02 M iodine solution. For a dragee of "Gerasfit" the deviation in the content of medicinal substance averaged ± 5, 45%, on The State pharmacopoeia XI - ±15%. And in a dragee "Gerask" the deviation in the content of medicinal substance in a dragee averaged ± 4,2%, a limit on The State pharmacopoeia XI - ± 15%.
Dissolution. For a dragee of Gerasfit"and Gerask"dissolution was carried out according to The State pharmacopoeia XI, edition 2, P. 159. Used the "device the rotating basket". The dissolution environment for tannins and ascorbic acid - purified water. capacity- 300 ml, the basket rotation speed of 100 rev/min. Dissolution time of the active substances for 45 min. After 45 min. should go into solution from dragees content of at least 75% of the drug. dissolution of tannins within 88- 99%, ascorbic acid-83- 88% 76- phytin- 80.2% in dragee "Gerasfit." In the dragee "Gerask" dissolution of tannins made within 88- 99% for ascorbic acid-81- 90%.
Microbiological purity of dragees "Gerasfit"and "Gerask" assessed according to the requirements of The State pharmacopoeia XI, edition 2, P. 193 "Methods of microbiological control of drugs" and changes № 2 from 29.09.2005, the, category 3B. In the experiments, satisfactory results were obtained that meet the specified requirements.
Quantitation. Quantitative determination of biologically active substances in the dragees "Gerasfit" and "Gerask" was determined by titration of 0.02 M solution iodine - ascorbic acid; tannins titration with 0.02 M solution of potassium permanganate,
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phytin titration with 0.1M sodium thiosulphate. The quantitative content of active ingredients in dragee "Gerasfit" ranged in - ascorbic acid relative 0.0475 g to 0.0525 g; Tanning sub- stances from 0.0510 g to 0.0530 g; of the fitting from 0.0409 to 0.0440 grams of dragees in "Gerask" - ascorbic acid-from 0.0480 g to 0.0510 g; Tanning substances from 0.0510 g to 0.0518 g, based on the average weight of the pellet.
Acute toxicity study dragees " Gerasfit" and "Gerask".
To conduct the experiment, dragees prepared in two formulations. To determine the toxicity of dragees "Gerasfit" and "Gerask" test was carried out on healthy white mice of both sexes weighing 19 to 21 grams, which previously held no test. 24 hours before the test and during the meeting the animal is in a room with a constant temperature. 2 hours before weighing and selection of animals for testing they have taken food and water [The State pharmacopoeia XI, edition 2].
The experiments were performed at the Department of Pharmacology and Clinical Pharmacy Tashkent Pharmaceutical Institute under the leadership of doctor of medical sciences, professor Kh.U.Aliev.
To study acute toxicity dragees "Gerasfit" and "Gerask" took 4 dragees, crushed them separately dissolved in 20 ml of purified water and used as a 2% solution. Experiments were performed on 38 mice weighing 18- 23 g of both sexes. 2% solutions are dragees "Gerasfit" and "Gerask" orally administered in a dose of 0.25 ml, 0.5 ml, 0.75 ml and 1 ml per weight in mice. Each dose was administered to 6 mice individually. Observation of the condition of the animals was performed for 2 days in the laboratory, then 12 days in vivarium conditions. Particular attention was paid to the general state of the mice: breathing, interest in food, the mobility and reaction to external stimuli. During the 14 days of observation in mice of any adverse reactions associated with the administration has not been studied pills. During the period of observation of animal deaths were observed. By this, the determination of the LD50 of drugs has not been possible.
Indicators of overall toxicity dragees "Gerasfit" and "Gerask" are shown in
tab. 1.
Table 1
Acute toxicity dragee "Gerasfit" and "Gerask"
Experience № The dose studied dragees "Gerasfit" and "Gerask" ml/ weight (ml/kg) The number of mice in the study group Results of the study dragees "Gerasfit" and "Gerask" acute toxicity, the remaining dead and surviving mice
The group received dragee "Gerasfit" The group received dragee "Gerask"
1 0,25 ml/weight (11,9 ml/kg) 6 0/6 0/6
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continuation of the table 1
2 0,5 ml/weight (23,8 ml/kg) 6 0/6 0/6
3 0,75 ml/weight (35,7 ml/kg) 6 0/6 0/6
4 1 ml/weight (47,6 ml/kg) 6 0/6 0/6
Besides, influence of preparations on a spasm of the isolated intestines, caused by chloride barium, in concentration 4 x 10-4 g/ml was studied. Dragee solutions in nutritious liquid added in concentration 1 x 10-4 - 8 x 10-4 g/ml.
Dragee solutions in concentration 4 x 10-4 and 8 x 10-4 g/ml are lowered by a spasm of the isolated intestines respectively by 20,1% and 32,7% in relation to the control. Therefore, the studied preparations possess noticeable spazmolytic action.
In a separate series of experiences studied the influences of a dragee prepared from dry extract of a Geranium colliniumon permeability of capillaries. Experiments were made on 18 mice weighing 21 - 23 g, of both sexes. Thus registered time of development of violations of permeability of capillaries of skin when drawing on it na xylol. According to a modified technique of K. N. Manakov [7] tripanovy blue was entered vnutribryushinno in a dose by 50 mg/kg in the form of 0,3% of solution. For receiving an inflammation in 20 minutes after introduction of tripanovy blue applied 0,02 ml on a back surface of back pads of mice n-a xylol.
Results of experience estimated on time of emergence of blue coloring of pads of mice in a drawing place n-a xylol.
Skilled animals were divided into 3 groups on 6 pieces: 1 group was control, 2-and 3 group - skilled in which animals received on 1 ml on weight. In 30 minutes after oral introduction of the studied preparations vnutribryushinno entered tripanovy blue. The control group in similar conditions received the physical. solution in the corresponding volume.
It was revealed that at mice of control group time of emergence of blue coloring of pads averaged 10,5±1,2 min. In skilled group where the studied dragees in a dose of 1000 mg/kg were entered, in 30 min. after introduction of preparations time of emergence of blue coloring of pads in mice increased by 29,5% and 37,1%, having made (on average) 13,6± 2,5 and 14,4± 1,7 min.
The obtained data are provided in tab.2. From the results of definition given in table 2 it is visible that the preparations "Gerasfit" and "Gerask" of a Geranium collinium possess the expressed strengthens the capillaries action.
Conclusions
1. It is developed for the first time structure and technology of a dragee on the basis of dry extract of a Geranium collinium, containing ascorbic acid, phytin with
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application of a drageeing copper and dragees of "Gerasfit" and "Gerask" are called conditionally.
Table 2
Influence of drugs "Gerasfit" and "Gerask" on the permeability of capillaries
The studied Number of Dose of the Strengthens the capillaries
№ drugs animals. drug minutes %
1 Control group 6 1 ml of purified water on the weight of animals 10,5±1,2 100
2 "Gerask" 6 1000 mg/kg 13,6±2,5 129,5 P<0,05
3 "Gerasfit" 6 1000 mg/kg 14,7±1,7 137,1 P<0,05
2. On the basis of the made experiments limits of rationing of a dragee are defined: appearance, authenticity, disintegration, average weight and a deviation from average weight, uniformity of dispensing, dissolution, microbiological purity, the quantitative content of active ingredients.
3. The studied new dosage forms from dry extract of a geranium collinium - a dragee of "Gerasfit" and "Gerask" were low- toxic at oral introduction.
4. The studied dragees possess noticeable spazmolytic and strengthens the capillaries action.
Literature:
1. Kurmukov A.G., Kuliyev Z.A., Urmanova F.F., Mamedova A.G. About anti-hypoxemic action of polyphenolic connections from underground bodies of a Geranium collinium. The pharmaceutical magazine - Tashkent, 2008, № 1, pp. 60-62.
2. Mamedova A.G. Farmakognozy studying of a Geranium collinium, growing in Uzbekistan. Abstract farm. sciences. - Tashkent, 2009. - 9 p.
3. Pazilbekova Z.T., Makhmudzhanova K.S., Zokirov S.H. Studying of the quantitative content of tannins in dry extracts of a Geranium collinium by method of permanganometry, titration and standardization of a dosage form. Pharmaceutical bulletin of Uzbekistan. Tashkent, 2012. № 1, pp. 33-35.
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4. Sharipova I.Sh., Makhmudzhanova K.S. Development of technology of a dragee on the basis of dry extract of a Geranium collinium with ascorbic acid. Pharmaceutical bulletin of Uzbekistan. Tashkent, 2012, № 1. p. 20-23.
5. The state pharmacopeia of the USSR - the XI prod., M., "Medicine", 1990, ed. 2, pp. 154-159.
6. Sharipova I.Sh., Ubaydullayev K.A., Saidvaliyev A.K., Makhmudzhanova K.S. Development of methods of identification of phytin and ascorbic acid in the dragees of "Gerasfit" and "Gerask" // The pharmaceutical magazine. Tashkent, 2012, № 3, pp. 6264.
7. Manakova K.M. A technique of quantitative studying of reactivity of capillaries of skin to action of inflammatory agents. Tajik Medical institute. Dushanbe, 1954, T. 13, ed. 1, pp. 27-32.
