Introduction. The abolition of smallpox vaccination after its elimination in 1980 led to a decrease in the immunocompromised immunity in humans. Zoonotic monkeypox, camelpox, buffalopox and cowpox viruses that are close to the variola virus also pose a danger to humans. In Russia today there are no effective and safe medicines for the prevention and treatment of smallpox and other orthopoxvirus infections in humans and animals. The Lady's mantle (Alchemilla vulgaris) is a promising source for the development of new antiviral drugs. Previous studies have found that Alchemilla vulgaris shows activity against influenza virus and herpes simplex virus.

Aim. The aim of this work was to study the chemical composition and antiviral activity of extracts from the roots and the grass of Alchemilla vulgaris against orthopoxviruses.

Materials and methods. Qualitative analysis of the samples was performed by high performance liquid chromatography. Quantitative analysis was performed using a complex of spectrophotometric methods. To determine the toxicity and antiviral activity of experimental samples from Alchemilla vulgaris in vitro, a transplantable Vero cell culture was used. Antiviral activity of the obtained preparations was evaluated by reducing the infectivity (titer) of orthopoxviruses in the monolayer of Vero cells infected with orthopoxviruses in the presence of preparations with different concentrations relative to the cell culture infected with orthopoxviruses without the preparations.

Results and discussion. It was shown that the experimental sample from Alchemilla vulgaris obtained by the method of ethyl acetate extraction from the roots of the studied plant and purified with chloroform contains mainly catechins and leucoanthocyanins (70 %). In parallel, extract from the raw mass of the grass of the plant purified with chloroform and ethanol contains the amount of flavonoids (71 %). Wherein the content of flavonoids in unpurified ethanol extracts from the roots and the grass of Alchemilla vulgaris composed 5 % and 6 %, respectively. It was revealed that purified preparations obtained from Alchemilla vulgaris roots when using ethyl acetate and ethanol as extractants showed antiviral activity against vaccinia virus and ectromelia virus, as well as preparations obtained from grass by ethanol extraction.

Conclusion. Thus, purified ethyl acetate extracts from the roots and ethanol extracts from the wet grass mass of Alchemilla vulgaris exhibit antiviral activity against orthopoxviruses in vitro. 

Introduction. Resveratrol is of scientific interest as a substance with a wide range of biological effects. However, its low bioavailability leads to limited use when administered orally. Therefore, the objective was to increase its solubility using various groups of excipients and create a solid dosage form. As a result of research, a group of twins was selected and the technology of manufacturing capsules containing 40 mg of resveratrol as a active substance was developed.

Aim. The development of a solid dosage form – capsules containing resveratrol, tween 80 as a solubilizer and other excipients.

Materials and methods. A composition with resveratrol, tween 80, glycerin, citric and ascorbic acids as stabilizers was developed. Methanol was used as a common solvent and was distilled off after complete dissolution of all components and obtaining a homogeneous mass. After adding olive oil (as a filler) to the resulting composition and a mixture of nipazole and nipagin (0.03 % by weight of the contents), the composition was manually mixed and poured into subsequently gelatin coated capsules for tightness. The quality indicators of the obtained capsules were studied in accordance with the requirements of the State pharmacopoeia XIV of Russian Federation (description, disintegration, dissolution, uniformity of dosage, residual organic solvents), as well as oxidation indicators.

Results and discussion. During the research it was found that the obtained samples of capsules containing resveratrol 40 mg/caps. as an active substance, and tween 80 as a solubilizer, had a good disintegration. The substance is well soluble in hydrochloric acid condition, which indicates its high bioavailability.

Conclusion. To produce capsules with resveratrol (40 mg/caps.) containing tween 80, glycerin, citric and ascorbic acids, excipients were selected according to studies that confirm the improvement of resveratrol bioavailability. The quality of the dosage form was assessed in accordance with the State Pharmacopoeia XIVth edition: it was shown that the use of Tween 80 as a solubilizer increases the release of resveratrol in the environment of gastric juice. 

Introduction. In the development and introduction of medicines into production, the aim of pharmaceutical manufacturers is to comply with the principle of «Quality-by-Design» (QbD). The International Council for Harmonisation (ICH) has created a number of GxP standards, which have become the regulatory framework for the development of documentation regulating the requirements for the development and production of drug products for countries focused on bringing their products to the world pharmaceutical market. The analysis of the system of regulation of pharmaceutical stages of development of new drugs in the territory of the Eurasian Economic Union was not considered, but for the formation of a systematic approach to the management of the process of pharmaceutical development it is necessary to describe them.

Aim. To analyze the possibility of applying the QbD principle to the process of drug development at domestic pharmaceutical enterprises.

Materials and methods. Content analysis of scientific publications, system and comparative analysis, sociological methods of research in the field of pharmaceutical development.

Results and discussions. Regulatory state requirements to the organization and conduct of drug development procedures are analyzed and described. A number of systemic and sectoral problems typical for domestic pharmaceutical manufacturers in the organization of the development and implementation of new drug products. It is established that one of the main problems for Russian enterprises was the organization of the process as a whole and its individual procedures. To solve the problem of organization of procedures for the development and implementation of new medicines, we formed a methodological support, developed on the basis of a systematic approach and international requirements from the quality system.

Conclusion. The main problem identified by the manufacturers is the lack of methodological support for the organization of the processes of pharmaceutical development and the introduction of new drugs in the part of research going to the stage of preclinical and clinical development. The decisions adopted by the Eurasian Economic Union do not affect such aspects of pharmaceutical development regulation as the organization of processes, their management and methodological support aimed at the implementation of the QbD principle. To solve this problem, we have developed guidelines for the implementation of the processes of pharmaceutical development and the introduction of new drug products, which allowed us to apply unified and formalized approaches to their organization. 

Introduction. The article deals with the aspects of the use of Medical Clays in Pharmaceutical Technology. A review of the traditional areas of application of Medical Clay, as well as highlighting new directions.

Text. One of the main problems of domestic industrial pharmacy is a narrow nomenclature of active pharmaceutical substances and excipients. Replenishment of the nomenclature occurs in two ways-through the synthesis of new chemical compounds or through the processing of natural raw materials of animal, plant or mineral origin. In the process of purification and processing of mineral raw materials, Medical Clays are obtained, which are now widely used as active pharmaceutical substances for the production of Enterosorbents, as well as auxiliary substances.

Conclusion. A review of perspectives and areas of use of Medicinal Clays have shown that at present, Medical Clays used in the three traditional areas: cutaneous application, application per os, application in pharmaceutical and food technology. A promising direction is the use of Medical Clays as transport drug systems. The study of this information array and its generalization has undoubted practical and scientific significance in modern pharmaceutical technology. 

Introduction. At the beginning of the twentieth century in the pharmaceutical community of Russia there were many problems. On the pages of the special press, such problems as the organization of pharmacy institutions (pharmacies, warehouses, shops, manufactures), directions and prospects for the development of the domestic pharmaceutical industry, its information support, relations within the pharmaceutical community, and the history of the development of world and domestic pharmaceutical science were discussed. However, more and more the subject of discussion was issues related to the fact of the extremely difficult situation of pharmacists-employees.

Text. The paper presents an analysis of the report of B. N. Saltykova «On the need to reduce working hours in pharmacies.» In it, the author presented a detailed and impartial analysis of the activities of pharmacies in the early twentieth century, summarized and formulated claims of pharmacists to government departments, pharmacy owners and the entire pharmaceutical community, substantiating, in particular, the need to reduce the working hours of pharmacy employees.

Conclusion. A detailed study of the contents of the report B. N. Saltykova leads to a clear understanding of the acuteness of issues related to unsatisfactory working and living conditions of pharmacists serving in Russian pharmacies at the turn of the 19^th and 20^th centuries. To solve this problem and establish normal work and life for pharmacists, a systematic approach is needed, as they would say now. In addition to the 8-hour shift and standardization of duties, changes were required at all levels of pharmaceutical education, changes in the legislative sphere, the search for consensus between the pharmacists-owners and pharmacists-employees, the appropriate labor protection of the pharmacist and the improvement of their life, and, most importantly, changes in society’s attitude to the pharmacist, that is, raising the prestige of this profession. 

Introduction. Walnut (Juglans regia L.) is a medicinal plant containing a large number of biologically active substances. A number of authors propose to use walnut leaves as medicinal raw materials, in which juglone, flavonoids, tannins, ascorbic acid and other substances are identified. Currently, a standardization technique for this type of raw material has been developed and proposed. However, the medicinal plant walnut can be a source of other types of raw materials, such as milky-waxed walnuts, walnut bark, and walnut partitions. These types of medicinal raw materials contain a large number of biologically active substances and have a great potential for pharmacological activity. Therefore, the study with the subsequent standardization of medicinal plant material of walnut fruits in the stage of milk-wax ripeness and walnut bark is relevant.

Aim. The aim of the study is to study the external signs, microscopy of raw walnut bark and walnut fruit in the stage of milky-wax ripeness and chemical composition of alcohol extract from these types of raw materials.

Materials and methods. Chromato-mass spectrometry and TLC were used in the work.

Results and discussion. When describing external signs and microscopy, diagnostic signs of both whole and crushed raw materials, and powder of walnut bark, and fruits of walnut in the stage of milky-wax ripeness were revealed. Alcohol extract obtained from medicinal plant raw materials walnut bark is a clear brown liquid. Alcohol extract obtained from medicinal plant raw materials of walnut fruit at the stage of milky-wax ripeness is a transparent, green-brown liquid with a fragrant odor.

Conclusion. Gallic acid was identified by TLC in walnut bark. Chromato-mass spectrometry in alcohol extraction from the fruit of walnut in the stage of milky-wax maturity was able to identify 17 compounds belonging to different classes of biologically active substances. Sugars, flavonoids, coumarin phenolic compounds, organic acids were identified. In alcoholic extraction from the bark of a walnut, marker compounds have been determined, the combination of which makes it possible to quickly identify this type of raw material using chromatography-mass spectrometry. 

Introduction. Recently, much attention has been paid to the primary assessment of the pharmacological effect of various drugs using in vivo and in vitro tests. It is known that such a medicinal plant as sea buckthorn, in its phytochemical composition is rich in natural antioxidants: carotenoids, tocopherols, flavonoids, ascorbic acid, etc. In some publications there is information about the antioxidant activity of sea buckthorn and fatty oil based on them. However, information on the comparative characteristics of the use of various methods for determining the antioxidant activity of this type of medicinal plant material and the results obtained are not found in the scientific literature.

Aim. The aim of this work was a comparative determination of the antioxidant activity of medicinal plant material of buckthorn fruits of various species of buckthorn.

Materials and methods. The total antioxidant activity of water and water-alcohol extracts from the fruits of sea buckthorn fruits was determined using various techniques recommended in the literature. The antioxidant activity of the extracts was determined by permanganometric titration, in vitro inhibition of adrenaline autooxidation, and also in a biological model, Parametium caudatum cell culture.

Results and discussion. The effect of the extractant polarity on the value of antioxidant activity was studied. It was found that the highest content of antioxidants in the extraction is observed when using 96 % ethanol as an extractant.

Conclusion. Using three methods, the prospects of using sea buckthorn fruits and preparations based on them as a source of antioxidants are shown. 

Introduction. Human Immunodeficiency Virus (HIV) is one of the main socially significant infection all over the world. HIV-positive patients take medical care, including antiretroviral drugs (ARVs) pharmacotherapy. Like all drugs, ARVs have lots of side effects that should be taken when prescribing drugs as part of highly active antiretroviral therapy. There are many cases when side effects of ARVs caused patients to enter the toxicology department. Therefore, the development of new methods for the analysis of ARV in biological fluids for the timely diagnosis of treatment of poisoning of this group of drugs is relevant today.

Aim. The aim of this study is development of screening analysis of atazanavir, abacavir, nevirapine, ritonavir, lopinavir, zidovudine, darunavir and efavirenz in the urine to identify these drugs as possible toxicants for poisoning by high-performance liquid chromatography with tandem massselective detection (HPLC-MS/MS).

Materials and methods. Identification of ARV was performed by HPLC-MS/MS. Methanol precipitation method was used as a sample preparation.

Results and discussion. The optimal conditions for sample preparation, chromatographic separation, and mass-spectrometric detection were selected to determine the studied ARVs. This method was tested on urine samples from patients in the Department of Acute Poisoning and Somatopsychiatric Disorders (OOSPD) with acute ARV poisoning.

Conclusion. This screening method for analyse atazanavir, abacavir, nevirapine, ritonavir, lopinavir, zidovudine, darunavir and efavirenz in human urine has been developed by HPLC-MS/MS. The developed method can be used to identify these drugs as possible toxicants in case of poisoning. The prospect for the development of the topic is the inclusion of new molecules in the method and quantitative determination of the studied ARVs. 

Introduction. Multicomponent oral drugs containing salbutamol, bromhexine, ambroxol and guaifenesin have a mucolytic, expectorant and bronchodilator effect. The development method for determination substances in biological fluids is a main procedure for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs. There is no published data of the determination of bromhexine, ambroxol and guaifenesin, but there a lot of published methods for divided determination analytes in a biological fluid. This study presents the development and validation of a method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human blood plasma by high performance liquid chromatography with tandem mass spectrometric detection. A sample preparation was perfomed by solid-phase extraction. Deuterated derivatives were used as internal standards.

Aim. The aim of the study is to develop a method for the quantitative determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection for performing the analytical part of pharmacokinetic studies.

Materials and methods. Determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection. A sample was prepared using solid-phase extraction.

Results and discussion. The method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, limit of quantification, carry-over and stability.

Conclusion. The method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma was developed and validated by HPLC-MS/MS. The analytical range of the was 0.1–20 ng/mL in plasma for salbutamol, 0.25–25 ng/mL in plasma for bromhexine, 0.075–3 ng/mL in plasma for ambroxol, and 10–2000 ng/mL in plasma for guaifenesin. Method could be applied to determination of salbutamol, bromhexine, ambroxol and guaifenesin in plasma for PK and BE studies.