O. I. Stepanova

Ribavirin has been used as an antiviral agent to treat a variety of viral infections since the 1970s. Over the past few decades, studies have been conducted on the pharmacology of ribavirin, and the possibility of its use in new indications has been explored. According to the results of a number of studies, ribavirin efficacy in the therapy of malignant neoplasms of various genesis has been proven. Furthermore, due to the complexity of brain tumor therapy using surgical methods, targeted delivery of ribavirin to the brain becomes a promising alternative to existing treatment methods. Targeting of active pharmaceutical ingredient (API) to the brain tumor is achieved by intranasal drug delivery via a Nose-to-Brain mechanism. In addition, using this delivery mechanism, it is possible to reach the brain while bypassing the blood-brain barrier (BBB), thus avoiding the effects of the first passage through the liver. Despite the significant advantages of the method, there are limiting factors to its application - mucociliary clearance, which aims to remove foreign bodies from the surface of the nasal mucosa. In situ, systems are able to reduce the intensity of interfering factors on API and allow the achievement of maximum bioavailability during intranasal administration.

Introduction. The use of synthetic drugs is associated with a number of side effects. When choosing a therapy to correct symptoms and treat dental diseases such as stomatitis, periodontitis, gingivitis, cheilitis, it is preferable to use herbal medicines in combination with traditional therapy, which would improve the resistance of periodontal tissues to pathogenic microorganisms. Herbal preparations are highly effective and well tolerated, which allows them to be used in modern medicine.Aim. To develop a medicinal collection with antimicrobial, anti-inflammatory, and wound-healing effects.Materials and methods. The following substances and reagents were used as research materials: Achilleae millefolii herba, Bidentis tripartitaе herba, Alni fructus, Anisi vulgaris fructus in a ratio of 1 : 1 : 1 : 1, diclofenac sodium, ascorbic acid, phosphate buffer, sodium citrate, luminol, iron (II) sulfate, heparinized blood, zymosan, saline solution, 2 % formalin solution, 10 % neutral formalin solution, hematoxylin, eosin. Antimicrobial activity was studied by comparing growth retardation of pathogenic microorganisms, antioxidant activity was studied on a chemoluminometer HLM-003 (Russia), hematological tests on mice were carried out using the ImageJ software package, Sysmex KX-21N (Sysmex, Japan), Leica RM 2145 microscope (Leica Biosystems Nussloch GmbH, Germany), binocular microscope Leica CME (Leica Biosystems Nussloch GmbH, Germany).Results and discussion. The evaluation of the anti-inflammatory, antioxidant, wound healing and antimicrobial activities of the plant herbal mixture was carried out. According to the results of the experiment, it was found that the herbal mixture has moderate antioxidant, wound healing and pronounced anti-inflammatory activity comparable to the comparison drug.Conclusion. A herbal mixture has been developed that has anti-inflammatory, antimicrobial and regenerating effects.

Taking into account the current Product specification file, the aim of the work was to develop the composition and technology for obtaining effervescent tablets based on solid dispersions of furazolidone in the form of an aqueous solution for external use.Materials and methods. The used substances were: furazolidone, anhydrous sodium carbonate (chemically pure), polyvinylpyrrolidone-24000±2000 (chemically pure), malic acid (analytically pure), tartaric acid (chemically pure), citric acid (chemically pure), sodium benzoate (chemically pure), ethyl alcohol 96% (chemically pure), purified water. Preparation of granulates is separate wet granulation in a fluidized bed (Mycrolab, BOSCH, Germany). Obtaining tablets is the process of pressing on a manual hydraulic test press (“PRG”, VNIR, Russia). The dependence of disintegration, abrasion capacity and crushing resistance on compacting pressure was investigated. Technological parameters of granulates, еру obtained effervescent tablets, shelf life and storage conditions were investigated according to the State Pharmacopoeia of the Russian Federation XIV^th ed.Results. Two compositions of effervescent tablets containing solid dispersions of furazolidone as an active substance were obtained, which, when dissolved in 100 ml of water at room temperature (20°C), form a solution of furazolidone with a concentration of 0.004% in less than 5 minutes. The method of quantitative determination of the furazolidone content in the effervescent tablets was validated. A complex of physicochemical methods for the analysis of tablets was carried out. Quality standards have been developed. The developed compositions stability of instant tablets during storage during accelerated and long-term tests has been experimentally confirmed. The preliminary shelf life and storage conditions have been determined.Conclusion. The result of technological and chemical-pharmaceutical research is the creation and evaluation of the quality of a new instant furazolidone dosage form as effervescent tablet formulations.

Introduction. Treatment of infectious and inflammatory diseases demands active substances (AS), characterized by low resistance of microorganisms, high specificity of the mechanism of action and a wide range of antimicrobial activity. Though furazolidone (FZ) – AS meets these criteria, however, practically insolubility in water significantly limits its use. Use of the solid dispersion method (SD) could increase the solubility and dissolution rate of AS with low water solubility. revious studies indicate an increase in the solubility and dissolution rate of FZ in water from SD with polyvinylpyrrolidone-24 000 (PVP-24 000) in a ratio with AS > 6 : 1 by weight. As a result, it becomes possible to introduce SD FZ into the composition of rapidly dissolving effervescent dosage forms, for example, granules for obtaining solutions for external use for the treatment of infectious and inflammatory diseases.Aim. Development of the composition and technology for producing effervescent granules based on solid dispersions of FZ for obtaining a solution for external use.Materials and methods. FZ substance, polyvinylpyrrolidone-24 000 ± 2000 (PVP-24 000 ± 2000), tartaric acid, malic acid, sodium carbonate anhydrous, ethyl alcohol 96 %, purified water. We provided the granules through fluidized bed granulation. The analysis of the obtained granules included the following parameters: description, granule size, loss in mass on drying, disintegration, uniformity of dosage according to GPМ 1.4.1.0004.15 "Granules". Then followed a qualitative and quantitative determination of AS and analysis of the pH of the aqueous solution of the granules. To study the stability and shelf life of the samples of granules, we laid them to the storage in accordance with GPМ 1.10009.15 "Stability and shelf life of drugs".Results and discussion. We developed he composition and technology of FZ effervescent granules for obtaining a solution for external use. Granules are obtained by separate granulation of the main (containing a SD AS) and acid components, followed by mixing in ratios that provide a solution of FZ with a concentration of 0.004 % in water at room temperature. Later we assessed the quality of the obtained compositions and determined, the shelf life (2 years) and storage conditions (in a dry, dark place at a temperature of 25 °C) of the developed compositions of granules.Conclusion. As a result of technological and chemical-pharmaceutical research using the SD method, we developed a new FZ dosage form – effervescent granules, which makes it possible to obtain an aqueous solution with a concentration of FZ 0.004 % in less than 5 minutes without heating. Based on the results of the work, an application was filed with Rospatent No. 2021105988 dated 10.03.2021, "Fast-dissolving dosage form of furazolidone and a method for its production".

Введение. На базе кафедр Сеченовского Университета разработан инновационный лекарственный препарат противомикробного и противопротозойного средства - метронидазола в форме шипучих таблеток. Совместно с ФГБНУ ВИЛАР была изучена на противомикробная активность разработанных быстрорастворимых таблеток. Метронидазол уже более 60 лет успешно применяется для лечения заболеваний ЖКТ, мочеполовой системы; активно используется в стоматологической и дерматологической практике. Вместе с тем в настоящее время на фармацевтическом рынке РФ отсутствуют быстрорастворимые лекарственные формы метронидазола, позволяющие пациентам использовать препарат как для внутреннего, так и для местного применения. Цель работы - определение антимикробной активности экспериментально разработанной новой для метронидазола лекарственной формы - шипучие таблетки с готовыми лекарственными формами метронидазола: раствором для инфузий и таблетками. Материал и методы. Метронидазол (субстанция), разработанные шипучие таблетки метронидазола (составы №2 и №3), их плацебо, бензоат натрия (вспомогательное вещество - скользящие), промышленно изготовленные таблетки и раствор для инфузий. Определение бактериостатической и фунгистатической активности изучали методом разведений. Использовали патогенные грамположительные и грамотрицательные бактерии, дрожжеподобные и мицелиальные грибы. При определении бактериостатической активности исследуемых образцов использовали мясопептонный бульон. При определении фунгистатической активности - жидкую среду Сабуро. Результаты. Полученные данные свидетельствуют о том, что все образцы, содержащие в своем составе метронидазол, по антимикробной (бактериостатической и фунгистатической) активности практически совпадают между собой и с активностью субстанции метронидазола, входящей в их состав, что косвенно подтверждает полное высвобождение субстанции из экспериментальных лекарственных форм и отсутствие образования с плацебо нерастворимых комплексов, которые могли бы препятствовать высвобождению метронидазола. Заключение. Проведенными исследованиями установлено наличие антимикробной активности у разработанных шипучих таблеток...

The aim of the work is to study the effect of solid dispersions using polyethylene glycols of various molecular weights on the solubility of metronidazole in water. Metronidazole is an antimicrobial and antiprotozoal drug. Its low solubility in water limits the use of metronidazole, causing technological difficulties and reducing its bioavailability. The solubility and release of the active substance from dosage forms can be increased using the solid dispersion methods. Solid dispersions are bi- or multicomponent systems consisting of an active substance and a carrier (a highly dispersed solid phase of the active substance or molecular-dispersed solid solutions) with a partial formation of complexes of variable compositions with the carrier material.Materials and methods. The substance of metronidazole used in the experiment, was manufactured by Hubei Hongyuan Pharmaceutical Technology Co., Ltd. (China). To obtain solid dispersions, polyethylene glycols of various molar masses – 1500, 2000 and 3000 g/mol – were used. The solid dispersions were prepared by “the solvent removal method”: metronidazole and the polymer were dissolved in a minimum volume of 96% ethyl alcohol (puriss. p.a./analytical grade) at 65±2°C, and then the solvent was evaporated under vacuum to the constant weight. A vacuum pump and a water bath were used at the temperature of 40±2°C. The dissolution of the samples was studied using a magnetic stirrer with heating, and a thermostatting device. The concentration of metronidazole was determined on a spectrophotometer using quartz cuvettes at the wavelength of 318±2 nm. To filter the solutions, syringe nozzles were used, the pores were 0.45 μm, the filter was nylon. Microcrystalloscopy was performed using a microscope with a digital camera. The optical properties of the solutions were investigated using a quartz cuvette and a mirror camera (the image exposure – 20 sec).Results. Obtaining solid dispersions increases the completeness and rate of the metronidazole dissolution. The solubility of metronidazole from solid dispersions increases by 14–17% in comparison with the original substance. The complex of physical-chemical methods of the analysis, including UV spectrophotometry, microcrystalloscopy and the study of the optical properties of the obtained solutions, makes it possible to suggest the following. The increase in the solubility of metronidazole from solid dispersions is explained by the loss of crystallinity and the formation of a solid solution of the active substance and the solubilizing effect of the polymer with the formation of colloidal solutions of metronidazole at subsequent dissolution of the solid dispersion in water.Conclusion. The preparation of solid dispersions with polyethylene glycols improves the dissolution of metronidazole in water. The results obtained are planned to be used in the development of rapidly dissolving solid dosage forms of metronidazole with an accelerated release and an increased bioavailability.

Разработка состава липосомальной лекарственной формы гидрофобного производного индолокарбазола

Определена микробиологическая активность раствора нафтифина гидрохлорида в комбинации с полиэтиленгликолями (ПЭГ-400 и ПЭГ-1000) в сравнении с имеющимся на рынке зарубежным лекарственным препаратом «Экзодерил». По результатам исследования фунгистатическая активность в отношении Candida albicans АТСС 10231 и разработанного раствора (минимальная подавляющая концентрация) в 2 раза превышает фунгистатическую активность раствора «Экзодерил».

Indomethacin, a non-steroid anti-inflammatory drug (NSAID), has been used in different spheres of medicine since the 1960s. It is successfully administered as an anti-inflammatory and pain-relieving medication in rheumatoid and other diseases. According to recent research, indomethacin may become a promising drug enhancing endogenous remyelination in patients with multiple sclerosis. Also, indomethacin affects cell proliferation and invasion, thus it is used to manage pancreatic cancer in patients with hyperglycemia. In addition, indomethacin can inhibit protein synthesis in colorectal carcinoma and other types of cancer cells. The article reviews modern indomethacin medications and the different dosage forms on the Russian pharmaceutical market. Indomethacin poor water solubility is one of the reasons for decreasing its biopharmaceutical characteristics. According to the conducted research, a prospective way to improve indomethacin solubility and bioavailability is the Solid Dispersion (SD) method. SDs are bi- or multicomponent systems consisting of the drug and the carrier. They are a highly dispersed solid phase of the drug or molecular-dispersed solid solutions with a partial formation of a variable composition complex and a carrier. The article provides a brief overview on different aspects of obtaining, investigating, and applying indomethacin SDs with various polymers.