Резюме
Марченко М.В., Крутських Т.В., Тіманюк В.О. Термогравіметричні дослідження глісульфазиду і діакамфу та гранул на їх основі.
Проведено термогравіметричний аналіз глісульфазиду і діакамфу та гранул на їх основі. Встановлено відсутність їх взаємодії у готовій лікарській формі та визначено температурні режими ведення технологічного процесу виробництва.
Ключові слова: термогравіметричний аналіз, температура розкладу, глісульфазид, діакамф, гранули.
Резюме
Марченко М.В., Крутских Т.В., Тиманюк В.А. Термогравиметрические исследования глисульфазида, диакамфа и гранул на их основе.
Проведен термогравиметрический анализ глисульфазида, диакамфа и гранул на их основе. Установлено отсутствие их взаимодействия в готовой лекарственной форме и определены температурные режимы ведения технологического процесса производства.
Ключевые слова: термогравиметрический анализ, температура разложения, глисульфазид, диакамфа, гранулы.
Summary
Marchenko М.V., Krutskikh Т.V., Тimanuk V.O. Thermogravimetric investigations of glisulfazidum, diacamphum and granules on their basis.
The thermogravimetric analysis of glisulfazidum, diacamphum and granules on their basis has been conducted. The absence of their cooperation in the finished dosage form has been established and the temperature conditions of the technological process of manufacturing has been defined.
Key words: the thermogravimetric analysis, temperature of decomposition, glisulfazidum, diacamphum, granules.

УДК 615.453.3:615.014.21:615.011.4

Национальный фармацевтический университет (Харьков) 61002, г. Харьков, ул. Пушкинская, 53
National University of Pharmacy (Kharkov) Ukraine, 61002, Kharkov, 53, str. Pushkinska

kosmich_no_limit@inbox.ru

Introduction. Diabetes - a disease of the endocrine system, caused by an absolute or relative deficiency in the body of the pancreas hormone - insulin, which manifests in profound disorders of carbohydrate, fat and protein metabolism. Recent years are characterized by rapid growth of diabetes morbidity around the world and in Ukraine - especially. Diabetes is extremely common disease in the world, in 2010, diabetes suffered about 250 million people. Therefore, the creation of drugs to treat this disease is relevant and timely [7].

Connection of the work with scientific programs, plans, topics.

The research is carried out according to the plan of scientific research work of the National University of Pharmacy ("Technology of reception original and combined pharmaceuticals in various dosage forms," state registration number 0108U009174) and Problem Commission "Pharmacy" Of the Ukrainian Ministry of Health.

The aim of the work. The aim of the work is studying temperature modes of active, auxiliary substances and granules based on them.

Materials and methods of the research.

Thermogravimetric analysis is used in pharmaceutical technology in the study of possible chemical interactions of dosage form components and substantiating the drying temperature regimes [3]. Every substance that is a part of the solid dosage form has a characteristic thermal behavior, which depends on its chemical structure. Therefore, studying their decomposition temperatures the properties of both, the individual substances and their mixtures can be set [11].

On the basis of glisulphazide and diacamph we have scientifically and experimentally confirmed the composition of a medicament for the treatment of type 2 diabetes [4]. When creating a drug the possibility of interaction between the components that make up its composition must be considered. This interaction can lead either to a strengthening of pharmacological activity or to its complete absence. This is especially important for the drugs, at which production it is necessary to use high temperature. Therefore, at the choice of the production process temperature conditions the behavior and interaction of the drug components at temperature elevation should be studied comprehensively [9,10].

The objects of study were samples of active ingredients (glisulphazide and diacamph), and their combination in the form of granules.

Application of wet granulation method in the production of granules involves their thermal drying that can affect the physical, chemical, technological and pharmacological properties of the drug.

Obtained results and their discussion. Determining the drug drying temperature was performed using thermogravimetric analysis, during which observed the dependence of the sample weight change on temperature. Each substance has a characteristic thermal behavior, so this way both individual agents and multicomponent systems can be explored and set the mode of granules thermal treatment. The following samples have been subjected to the above mentioned analysis: glisulphazide, diacamph, potato starch, calcium stearate and developed granules. Thermogravimetric study was conducted at the NUPh Department of Physics led by prof. V.O.Timanyuk under the conditions of dry substances heating [5,6,7].

The analysis was performed on derivatograph Q-1000 of F. Paulik, J. Paulik, L. Efdey system with platinum-platinumrhodium thermocouple by heating samples in ceramic crucibles from 18 ° C to 1000 ° C in air. Heating rate was 20 ° C per minute [3].

As standard used calcined aluminium oxide. Weight of the samples was 50 mg. Recorded curves: T, TG, DTA and DTG. Curves: T - temperature change, TG - weight change, DTA - differential curve of thermal effects change, DTG - differential weight curve. The samples derivatograms are shown in Fig. 1 - 4.

From Figure 1, which shows glisulphazide derivatogram it can be assumed that by the 205 ° C the sample is not undergoing any visible changes. Further decomposition process takes place in two stages. The first stage occurs at temperatures from 233 ° C to 275 ° C. At this an endothermic effect is observed (sample melting) at 233 ° C with losing about 2% of the sample mass. The second stage begins at a temperature of 275 ° C, and characterizes by exothermic reaction at 275 ° C, losing about 45% of the substance. At this the sample burnout occurs.

Figure 2, on which diacamph derivatogram is given, allows assuming that up to 227 ° C there is no noticeable change of the substance. At temperature increasing the sample decomposes in two stages. The first stage takes place at temperatures from 250 ° C to 380 ° C. Thus observe two endothermic reactions at 250 ° C and 272 ° C with losing 8% and 12% of the sample respectively. The second stage begins at 380 ° C and is characterized by the sample burnout and losing almost 97% of the sample mass.

Figure 3, which shows potato starch derivatogram, allows assuming that up to 60 ° C there is no noticeable change of the substance. The destruction of the sample actively occurs at 110 ° C, when there is a maximum speed of splitting. When heated to 190 ° C the sample loses approximately 16% of its mass, and to 295 ° C - about 39%. Exo - and endothermic reactions during heating do not occur.

Figure 4 shows derivotogram of the developed granules under the conditional name "Gliakampf". From the figure graphic data it can be assumed that up to 155 ° C any significant changes to the model occurs. And from 190 ° C the sample weight losing starts. Decomposition of the drug occurs in 3 stages. The maximum rate of decomposition of the granules at the1^st stage coincides with granules melting at 207 ° C. The second stage begins at 265 ° C, the third - at 320 ° C. The second and third stages are not accompanied by any exo-and endothermic processes.

Analyzing the data obtained during thermogravimetric study, we can conclude that glisulphazide and diacamph substances are heat-stable and do not contain absorbed moisture. Potato starch, in contrast, is a thermolabile substance in which the conversion process begins at 60 ° C. In the mixture of substances is observed some lower temperature conversion compared to the active substances, but higher than the temperature of the starch.

Thus, we can conclude that the granules drying temperature should not exceed 60 ° C due to the fact that this is the highest temperature at which excipients remain stable [1,2].

Conclusions: 1. Absence of interaction between active substances and excipients of the medicinal product has been established. 2. The temperature regimes of obtaining glisulphazide, diacamph and their mixtures granules for further researches have been set. 3. The chemical and physical transformation of medicinal substances and excipients under the influence of high temperature has been studied.

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