Background: We have synthesized three 5-R-1-aryl-1,5-dihydro-4Н-pyrazole(3,4-d)pyrimidine-4-one derivatives that previously have demonstrated powerful anticonvulsant activity. A great number of physicochemical factors are known to influence on bioavailability and stability of active pharmaceutical ingredients. Therefore the purpose of research was to determine the effect of purification technology and dispersibility of 5-R-1-aryl-1, 5-dihydro-4Н-pyrazole (3,4-d) pyrimidine-4-one derivatives on their anticonvulsant activity.Methods: The anticonvulsant effect of this compounds was studied in a model of pentylenetetrazole-induced seizure in mice.Results: The results obtained revealed the optimal solvent for recrystallization of compounds to be isopropanol: compounds, purified by recrystallization from isopropanol, had higher solubility in water and tween; also, they had a tendency to increase anticonvulsant activity. It was found that there is a significant dependence of the latter on compound’s dispersion - the smaller the size of crystals the higher anticonvulsant activity.Conclusions: The dependence of anticonvulsant activity of compounds on the degree of dispersion was proved: the smaller particle size the higher anticonvulsant activity. This can be explained by fast dissolution of fine-dispersed substances, thus increasing the bioavailability if the compounds studied.

У результаті цілеспрямованого синтезу знайдено перспективну субстанцію для створення лікарського засобу протисудомної дії-симетричний дибензиламід малонової кислоти. Характерним для цієї субстанції є те, що ця речовина синтезується у одну стадію з високими виходами з доступних хімічних речовин, .в експериментах на тваринах проявляє протисудомну активність при низькій токсичності. Метою нашої роботи було визначення оптимальних умов синтезу N,N-дибензиламіду малонової кислоти та масштабування методики у промисловому виробництві. Методи дослідження. Отримали N,N-дибензиламіду малонової кислоти шляхом синтезу. Оцінку чистоти здійснювали хроматографічно. Проведено мікрокристалоскопічні дослідження фізико-хімічних властивостей синтезованого дибензиаміду малонової кислоти. Результати дослідження. У результаті досліджень опрацьовано методику синтезу субстанції N,Nдибензиламіду малонової кислоти в умовах промислового підприємства, досліджено вплив часу реакції та співвідношення реагентів на вихід та чистоту цільового продукту. Висновки. Опрацьовано методику синтезу субстанції N,N-дибензиламіду малонової кислоти в умовах промислового підприємства з урахуванням сучасних вимог до якості та безпеки активних фармацевтичних інгредієнтів. Обгрунтовано вибір вихідних речовин, розчинника, умов синтезу та очистки для забезпечення належної чистоти та високого виходу кінцевого продукту. Одержані результати можуть бути використані для синтезу субстанції N,N-дибензиламіду малонової кислоти в умовах промислового підприємства Ключові слова: синтез, N,N-дибензиламід малонової кислоти, протисудомна активність, час реакції, співвідношення реагентів In result of a targeted synthesis, a promising substance for new anticonvulsant drug creationsymmetrical dybenzyl amid of malonic acidwas found. The ability to be synthesized in one stage from available reagents and with high yield, as well as to show in animal experiments anticonvulsant activity with low toxicity is specific for the given substance. The aim of our research was to determine optimal conditions for synthesis of N,N-dybenzyl amid of malonic acid and to scale the method in industrial production. Methods. N,N-dybenzyl amid of malonic acid was obtained by synthesis. Purity was estimated using chromatographic methods. Crystals microscopy was carried out for study physical and chemical properties of the synthesized dybenzyl amid of malonic acid. Results. In result of research, the method of N,N-dybenzyl amid of malonic acid synthesis was elaborated under manufacturing conditions; the influence of the reaction latency and reagents ratio on the product yield was studied. Conclusion. The method of N,N-dybenzyl amid of malonic acid synthesis was elaborated under manufacturing conditions considering modern requirements to the active pharmaceutical ingredients quality and safety. The choice of the initial substances, solvent, synthesis and purification conditions was substantiated to ensure the final product's appropriate purity and high yield. The obtained results can be used for N,N-dybenzyl...

Considering the simplicity and ease of use, in recent years, more and more attention deserves medicated chewing gum (MCG), which plays the role of oral drug delivery system. Since this product remains in the oral cavity for a longer time than other oral medicines, the taste is one of the important features of the MCG. It is known, that one of the ways to correct and mask the taste of medicines is the addition of intense sweeteners, which not only affect the taste characteristics of the ready product, but also can influence the physic-chemical and technological properties of the active components. The aim of this work was the selection of the optimal intensive sweetener in the developed dental MCG with lysozyme hydrochloride and ascorbic acid. As natural flavourers, we studied natural and synthetic intensive sweeteners: potassium acesulfame, aspartame, sodium cyclamate, sodium saccharin, stevia and sucralose. The choice of flavouring agents was carried out using organoleptic methods for evaluating the taste with the help of numerical indexes by A. I. Tentsova and use of alphabetic and numerical indexes by I. A. Yegorov, and also by studying the crystallographic properties of intense sweeteners and their mixtures with active pharmaceutical ingredients. According to the obtained results, all compositions, except for the sample with sodium saccharin, had a corrective property and had a similar sweet-sour taste. However, not all of them had a long sweet aftertaste, which is very important for this dosage form. The highest numerical indices were samples of MCG with sodium cyclamate, stevia and sucralose. By conducting a microscopic analysis of mixtures of active pharmaceutical ingredients with the investigated intense sweeteners were predicted possible methods of obtaining the developed solid dosage form – the method of direct compression or the use of preliminary granulation. Taking into account the complex of the obtained results, sucralose has the best correcting and physic-chemical characteristics of all the investigated intense sweeteners.

Aim. The purpose of the work is to determine the bioadhesion indices of vaginal gel with resveratrol and hyaluronic acid, as well as the choice of the type and content of mucoadhesives in the composition. Materials and methods. As research objects samples of gels with different mucoadhesives in the composition were used. Among used mucoadhesives were: sodium alginate (FMC BioPolimer AS, Norway), methyl cellulose (Shin Etsu, Germany), Methocel – methyl cellulose with hydroxypropylmethyl cellulose (Dow Pharmaceutical Sciences, USA), OraRez® W-100L16 – vinyl methyl ether and maleic anhydride copolymer (BOAI, China). As a comparison drug, vaginal gel "Gynodec" (Yuriya-Pharm) was used. During the study, the rate of gel distribution, the degree of deformation under the influence of mechanical forces, the degree of the gel fixation on the surface of the mucosa and the adhesion ability of the samples have been determined. Results. The study has determined that sample No. 2 with sodium alginate has the highest distribution rate, which was 1.56 cm/min. The study of the fixation of samples on the surface of the model of the mucous was performed by the method of flow. The results have showed that the sample with sodium alginate has the closest value to the reference drug. The adhesive ability of samples with different sodium alginate contents was determined. The tensimetric study has found that at a concentration of 0.5 %, the force required to separate the surface is 6158 Pa. Conclusions. On the basis of the complex of physico-chemical studies, bioadhesion indicators of vaginal gel with resveratrol, depending on the type and concentration of mucoadhesives have been determined. According to the distribution parameters on the surface of the genital mucosa model, it has been found that the best properties compared with other types of mucoadhesives has a sample containing sodium alginate. The study by means of a strain gauge has found that the addition of sodium alginate at a concentration of 0.5 % would provide a satisfactory adhesive ability of the vaginal gel.

В даний час інноваційним напрямом фармацевтичної розробки є застосування методів підвищення біофармацевтичної ефективності та безпеки використання вже існуючих АФІ, в тому числі за рахунок їх включення у тверді дисперсії, в яких молекули речовини включаються в супрамолекулярні утворення за рахунок формування нековалентних зв'язків ексципієнтами. На сьогодні отримання твердих дисперсій розглядається як найбільш ефективний спосіб підвищення біодоступності при пероральному прийомі, в якому розчинення носія сприяє вивільненню АФІ зі швидкою його солюбілізацією. За даними літератури встановлено, що на сьогодні існує тільки емпіричний підхід до отримання твердих дисперсій. Метою роботи стало формулювання основних підходів до створення препаратів на основі твердих дисперсій з урахуванням сучасних напрямків розроблення складу та технології препаратів з важкорозчинними речовинами. Матеріали та методи. Для розробки методологічного підходу використовували зовнішній ситуаційний контент-аналіз прикладних методів підвищення біодоступності активних фармацевтичних інгредієнтів, що застосовуються при виробництві твердих лікарських форм. Результати. В ході виконання поставленої мети було запропоновано класифікацію типів твердих дисперсій залежно від структури і способу отримання, створено алгоритм з вибору способу отримання твердої дисперсії з урахування фізико-хімічних властивостей активних фармацевтичних інгредієнтів, який може бути використаний в технологічному процесі для посилення їх біодоступності. Також були виявлені критичні ланки при розробленні твердих дисперсій. Висновки. З урахуванням фізико-хімічних властивостей активних фармацевтичних інгредієнтів визначено алгоритм з вибору способу отримання твердих дисперсій, який може бути використаний в технологічному процесі для покращення їх біодоступності. На підставі результатів аналізу даних літератури та власних досліджень щодо фізико-хімічних характеристик активних фармацевтичних інгредієнтів та ексципієнтів, типу структури твердої дисперсії, виду розчинника та носія, запропоновано методологічний підхід до отримання твердих дисперсій, застосування якого дозволить оптимізувати процес розробки твердих лікарських форм Ключові слова: тверді дисперсії, біодоступність, спосіб отримання, структура, методологічний підхід, етапи розроблення

In order to guarantee qualitative medical and pharmaceutical care it is necessary for all participants of the process to provide consistent interconnected actions, including the use of modern approaches in pharmacotherapy, assessment of the urgent needs of the population in medicines (drugs), development and introduction of modern qualitative, safe and effective drugs into the market. Today, one of the key indicators in determining the population‘s need for drugs is the epidemiological indicators in a particular region and their dynamics. In recent years, the actuality of optimal and effective approaches developing in the prevention and treatment of socially significant diseases, including diabetes mellitus (DM), has been increasingly emphasized at the global level. All actions that are proposed for the development of standardized guidelines, treatment protocols, programs for on-time detection and prevention of diabetes are aimed at forming a system of measures are patient-oriented, based on understanding the patient‘s problems, lifestyle, habits, income and expenses for treatment, as well as other components associated with achieving optimal results for patients.

The aim of this work was to study the effect of glikverin based on voglibose and quercetin on lipid metabolism in experimental metabolic syndrome. Materials. The metabolic syndrome model was reproduced by keeping rats on a hypercaloric diet (containing 20 % fatty food and fructose ad libitum (1 g per day per 100 g of body weight as a 10 % aqueous solution) for 8 weeks. The content of complex carbohydrates in the daily diet of animals was 60 %. The following groups of rats were used: group 1 — intact control; group 2 — rats receiving a hypercaloric diet; group 3 — animals that were administered glikverin at a dose of 50 mg/kg on the background of hypercaloric diet, groups 4–6 — animals that were administered comparison drugs on the background of hypercalorie diet: quercetin substance at a dose of 50 mg/kg, the voglibose substance at a dose of 0.06 mg/kg and standard drug — metformin at a dose of 60 mg/kg. The study drugs were administered simultaneously with the hypercaloric diet intragastrically for 8 weeks. Lipid metabolism was assessed by body weight gain, total cholesterol, triacylglycerols, low- and highdensity lipoprotein cholesterol, and serum TNF-α levels. Results. It was found that the combined product glikverin reduces body weight gain by 66%, which is probably specified by the action of its component component voglibose, which slows down the breakdown and absorption of carbohydrates in the intestine. The results of the study of lipid metabolism in blood serum showed that the combination of voglibose and quercetin in the combined agent leads to the summation of their pharmacological effects. Under the influence of glikverin, the content of total cholesterol decreased by 1.7 times, LDL-C and TAG - by 1.6 and 2.2 times, respectively, the level of HDL-C increased by 46%. Comparative analysis showed that the pronounced antiatherogenic effect of the combined agent is due to the effect of both components, with a predominant effect on the lipid metabolism of quercetin. The revealed hypocholesterolemic and hypolipidemic action provide an antiatherogenic effect. The severity of this effect, which provided glikverin, significantly exceeded the comparison agents quercetin, voglibose and metformin. The combination of voglibose and quercetin also reduced by 38% the content of TNF-α - an inductor of insulin resistance in obesity. The obtained results substantiate the expediency of further pharmacological study of the antidiabetic properties of glikverin as a promising tool for the treatment of metabolic syndrome and type 2 diabetes.

Characteristics and relevance of article topic. Analysis of the literature data shows that the thioctic acid preparations are widely used in the treatment of various diseases. At it’s parenteral application inter- and intraindividual level at the plasma can vary significantly. Therefore, the bioavailability of thioctic acid according to the results of clinical researches is only 30% and efficacy largely dependent on the technological features of the dosage form manufacturing process. The goal of paper was researches of the thioctic acid physico-chemical properties for development of composition and technology of solid dosage form with improved bioavailability. Thioctic acid was the object of the study. The complex of physical, chemical and technological tests were used during researches: microscopic, thermal analyzes studies of bulk density, flowability, compression ratio, hygroscopicity, dissolution. Conclusions. According to thermal analysis, thermal stability of thioctic acid sample has been established within 20–180 °C. The results can be used for explanation the temperature regime in the preparation of solid dispersions of thioctic acid by the melting method. Solubility determination according to SP of Ukraine II-ed. and microscopic method showed that the substance is readily soluble in 96% ethanol, which leads to the conclusion about the possibility of preparation thioctic acid solid dispersions by dissolution method. During researches were established physico-chemical and technological properties of the thioctic acid substance, produced by Shanghai modern pharmaceutical Co., LTD (China). Were established that the substance is hygroscopic as evidenced by the change in appearance and weight. It was determined that the substance does not have a satisfactory yield (Carr index – 1,39, slope angle – 60°), compression ratio is 0,495, which is indicative of the lack of sample strength after the removal of pressure. The results of the studies suggest that the physicochemical properties of the substance needed modifications in the manufacture of solid dosage forms with thioctic acid.