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Section 5. Medical science
DOI: http://dx.doi.org/10.20534/ESR-17-3.4-18-20
Azizova Matluba Abduholikovna, Institute of Chemistry of Plant Substances named after S. Y. Yunusov Academy of Science of the Republic of Uzbekistan, Uzbekistan
Djalilov Khabibulla Karimovich, Head department of Quality Control of Drugs and Medical Equipment
Sagdullaev Shomansur Shaxsomdovich, Institute of Chemistry of Plant Substances named after S. Y. Yunusov Academy of Science of the Republic of Uzbekistan, Uzbekistan E-mail: [email protected]
Selection of the optimal composition and rational technology of core tablets of Aksaritmin
Abstract: Improving the provision of health care needs is directly related to the creation of drugs with targeted action and low toxicity. From this point of view, medicines with natural origination play a huge role in the pharmaceutical industry. The development of the aksaritmin tablet obtained on the basis of the northern fighter provides an opportunity to increase a number of antiarrhythmic drugs with high efficiency and low toxicity.
Keywords: Aksaritmin, Northern fighter, wet granulation, technological properties, pressing, residual moisture.
Improving the provision of health care needs is directly related to the development of medicines with high efficiency. From this point of view, purposeful search for medicinal products from plant raw materials is carried out at the Institute of Chemistry of Plant Substances of the Academy of Sciences of Uzbekistan, and as a one of the results of these researches a sum of alkaloid bases was extracted from rhizomes with roots of A.septentrionale (Northern fighter), an aksaritmin with antiarrhythmic action [1; 2; 3].
The selection of the optimal composition and development of a rational technology of the tablets of an aksaritmin is a very important stage in the tablet technology.
At the stage of developing a solid dosage form of aksaritmin, the physicochemical and technological characteristics of the active substance were studied in advance and displayed in the table 1 [4; 5; 6].
Table 1. - Characteristics of aksaritmin substance
Properties Characteristics
Appearance of powder Bright-yellow powder with creamy shade and specific odor
Form of substance particles Anizodiametric polycrystalls in the form of prism
Bulk debsity, kg/m 3 429 ± 0,015
Flowability, kg/s 1,47 x 10-3 ± 0,03
Moisture content,% 3,14 + 0,1
Fractional composition,%
- 2000 + 1000 11,09
- 1000 + 500 15,16
- 500 + 250 40,13
- 250+ 135 26,92
- 135 6,70
Results of the study. It has been established that the substance of aksaritmin is practically not flowable (1.47-10-3 kg) and has a small bulk density (429 kg/m 3). According to the results of the test on physicochemical and technological characteristics of the substance, it was evident that it is impossible to receive core tablets without the usage of the excipients.
In our previous studies, the selection process of auxiliary substances in various combinations for obtaining core tablets by the direct compression method was carried out [7].
On the basis of the conducted studies, it was found that the method of direct pressing with auxiliary substances in various combinations for the production of aksaritmin tablets significantly improves
Selection of the optimal composition and rational technology of core tablets of Aksaritmin
the technological properties of the compressed mass and allows the carrying out of a normal pressing act. However, the quality of these tablets was comparatively low, the indexes like strengths to break and friction didn't meet the requirements, which caused to the doubt on the possibility of obtaining tablets in large-scale production.
In addition, during the research tablets of the aksaritmin the homogeneity of active substance did not meet the requirements due to the small amount of aksaritmin. The uniformity of dosage is a characteristic of the distribution of the active substance per unit of the dosage of the drug. During the operation of the tablet machine, the pressed mass in the batcher was stratified due to vibration of the machine. The stratification of the compressed mass occurred due to the difference in the bulk density of the ingredients, as well as the spread of the particles in size. It can lead to uneven dosing of the active ingredient in the tablets. In order to improve the technological properties of the tablet mass, the possibility of obtaining pellets with the method of moist granulation was studied. In the experiments we used compressed mass of 4 compositions with the subsequent study of the technological properties of the pressed mass and the physico-mechanical parameters of the tablets obtained from them. In this case, sucrose, glucose, lactose, ICC "Introcel", calcium carbonate and disubstituted calcium phosphate were used as fillers in various combinations. As a
disintegrant potato starch was used in amounts up to 1-5%, and as antifriction agent — 1% calcium stearate was chosen. Unlike the method of direct pressing, the decisive factor that guarantees the high quality ofthe target product is the conditions for carrying out the moistening process [8]. The most effective technological method of increasing the compressibility of powdered medicinal substances is the input of auxiliary substances possessing a binding and moisturizing ability into the tablet mass. As a moisturizing and binding component, 96% ethyl alcohol, 1-5% starch paste and purified water were used. Four compositions of the tablets of an aksaritmin 0.025 g, were prepared by the wet granulation method and selected for further studies, the compositions presented in Table 2.
The content of the technology lies in the fact that the calculated amount of the substance of the aksaritmin, sifted through a sieve with a pore diameter of 160 ^m, is mixed with the required amount of filler and moistened with a solution of the binding substance until mass with optimal moist is formed. The essence of the technology lies in the fact that, the calculated amount of the substance of the ansarhythm, sifted through a sieve with a pore diameter of 160 ^m, is mixed with the required amount of filler and moistened with a solution of the binding substance until an optimally moist mass is formed.
Table 2. - Compositions for making core tablet aksaritmin 0.025 g by the method of moist granulation
Ingredients Compositions
№ 1 № 2 № 3 № 4
Aksaritmin 0,025 0,025 0,025 0,025
Lactose 0,022 0,045 0,0458
Sucrose 0,021 0,0458 0,0908
Glucose 0,0208 0,045
Starch 0,03 0,003 0,003 0,003
Calcium stearate 0,0012 0,0012 0,0012 0,0012
5% paste of starch Needed amount Needed amount Needed amount Needed amount
Average mass 0,12 0,12 0,12 0,12
The wet mass is passed through a sieve with a hole diameter of 2500 ^m, the granules are laid out in a thin layer on a sheet of parchment paper and dried in an oven at 40-50 °C until getting the optimum residual moisture (1.6 ± 0.4). The dried mass is re-granulated by passing through a sieve with a hole diameter of 1000 ^m, the granules are blended with a mixture of potato starch and calcium
Table 3. - Technological properties of the press
stearate that previously sieved through a sieve with a hole diameter of 100 ^m [4; 5]. To assess the quality of the prepared granules which is obtained by the wet granulation method and will be used for making tablet drug form of axarhythmin 0.025 g, their technological properties were determined and the results are shown in Table 3.
mass obtained by the wet granulation method
Technological properties Unit of measurement № 1 № 2 № 3 № 4
Fractional composition: - 1000 + 500 ^m % 7,04 5,35 6,17 7,21
- 500 + 250 ^m % 43,17 39,94 45.46 38,21
- 250 + 160 ^m % 47,25 52,84 45,16 51,50
- 160 ^m % 2,54 1,87 3,21 3,08
Flowability 10-3 kg/s 3,11 4,26 3,87 5,74
Compressibility H 45,4 35,34 39,85 45,82
Angle of repose ° 52,6 44,18 49,92 27,85
Bulk density g/m3 735 558,23 549,82 637,48
Compression coefficient K 1,98 1,56 1,62 1,17
Moisture content % 3,2 2,76 2,11 4,6
The evaluation of the technological characteristics of tablets showed that, by using the wet granulation method for tablet making granules with necessary technological properties were obtained and the 4th composition for tablets was meet the requirements of GP XI [6].
Conclusion. Obtained tablets met the requirements of normative documents and wet granulation was chosen as a main method of obtaining tablet drug forms of aksaritmin.
References:
1. Sadikov A. Z., Sagdullaev Sh.Sh., Djahangirov F. N., Abdullaev N. S., Usmanova S. «Acsarythmine - new antiarrythmic preparation from rzhizome and roots of Aconitum septentrionale Roelle», 6th International symposium on the chemistry of natural compounds, 28-29 june - 2005, - P. 085, - Ankara-Turkey.
2. Sadikov A. Z., Sagdullaev Sh.Sh., Mullabaeva Z. U. Chromatographic Method of Purifying Substance ofAcsaritmin Preparation//2nd Annual Russian-Korean Conference: Current issues of natural products chemistry and biotechnology. - 2010. Russia - Novosibirsk, -P. 129.
3. Sadikov A. Z., Sagdullaev Sh.Sh., Mullabaeva Z. U., Otaeva Sh. A. Spectrophotometric Method of Analyses Substance of Acsaritmin Preparation//2nd Annual Russian-Korean Conference: Current issues of natural products chemistry and biotechnology. - 2010. -Russia - Novosibirsk, - P. 130.
4. Pharmaceutical development: the concept and practical recommendations.
5. Scientific and practical guide for the pharmaceutical industry/Ed. Bykovsky S. N., Vasilenko I. A., Shokhina I. E., Novozhilova O. V., Meshkovsky A. P., Spitskiy O. R. - M. Perot Publishing House, - 2015, - P. 472.
6. Belousov V. A., Walter M. B. - Basis of dosing and tabletting of medicinal powders, - Medicine. - 1980, - P. 213.
7. Emshanova S. V., Sadchikova N. P., Zuev A. P. On the control of the size and shape of particles of medicinal substances//Chemical-pharmaceutical journal. - 2007. - P. 41 - No. 1. - P. 41-49.
8. Alekseev K. V., KedikS. A., Blinskaya E. V., Lazereva E. E., Uvarov N. A., Alekseev V. K., Tikhonova N. V. Pharmaceutical technology. Solid dosage forms. - Moscow, - 2011. - P. 661-661 p.
9. Kuznetsov A. V. Selecting a humectant for making tablets which is used pre-granulation/Pharmacy - 2002. - No. 6. - P. 27-29.
DOI: http://dx.doi.org/10.20534/ESR-17-3.4-20-22
Dzharashtieva Dzan-Pago, Bulgakova Anastasia, Shevchenko Pert, Karpov Sergey,
Vishlova Irina Stavropol State Medical University, Russia Department of neurology, neurosurgery and medical genetics
E-mail: [email protected]
Modern methods of pharmacotherapy of generalized forms of epilepsy
Abstract: epilepsy is a chronic polietiologic disease, manifested by repeated unprovoked, seizures or other seizures, loss of consciousness and is accompanied by changes in personality [8]. Among the forms of epilepsy is one of the most common and dangerous forms of generalized seizures [1]. In recent years, ideas about generalized epilepsy have undergone significant changes: the features of focality in generalized epilepsy and the typical features of idiopathic generalized epilepsy with focal seizures. The relevance lies in the fact that the affinity of these forms is confirmed by genetic studies when one genetic disease, there are a variety of focal and generalized phenotypes in different members of the same family. This, of course, requires the search of new anticonvulsant agents for the successful treatment of various forms of epilepsy, including generalized, contributing to improve the quality of life. Keywords: epilepsy, generalized seizures, focal seizures, quality of life, drug with wide spectrum of action.
Purpose: to analyze the literature of the modern methods of pharmacotherapy in generalized forms of epilepsy.
Material and methods: analysis of data on the incidence of epilepsy among adult population of the Stavropol territory on 2010-2016. Using data on the number ofpatients in percentage, we can observe maximum growth by 2015, and begin decline by 2016.
2010 2011 2012 2013 2014 2015 2016 Figure 1.
Using data from diagnoses that were first installed, we can ob- Results: the incidence of epilepsy is between 50 and 70 per
serve the wave-like change of the data, with maximum values in 100 000 population, the prevalence is 5-10 cases per 1000 people. 2014, a downward trend in 2015 and 2016. It is believed that 1 or more seizures in the course oflife carry about
