The scientific and practical conference "Drug development and registration: Application of GLP Rules of the EAEU" was held online on December 17, 2021. The conference was organized by LLC "CPHA" and the research and production journal "Drug development and registration". The event was organized with the support of colleagues from Statandocs Academy.

In the work, on the example of the memoirs of Professor VN Ipatiev, the history of the revival of the chemical industry of the young Soviet Republic in the period from 1917 to 1927 is briefly presented. The first part of the article describes the first steps of the Soviet government to restore the domestic chemical industry. Realizing the importance of the chemical industry as an integral part of the state's defense complex, the government of the RSFSR began the consistent restoration of enterprises destroyed during the two revolutions and the civil war. With the organization of the Supreme Council of National Economy and the department of the chemical industry, systematic visits to chemical industry enterprises began with the aim of inspecting, re-equipping and launching them. All this happened in the most difficult conditions of the ongoing civil war and general devastation. The nationalization of small and large enterprises is briefly described, as well as the organization of the State Institute of Scientific and Technical Research (GONTI), a specialized publishing house, and various chemical cooperatives.

The new CA-310 is a convertible Karl Fischer titrator that can be easily switched from coulometric to volumetric measurement or vice versa, which allow to determine the water content from 1 ppm to 100 %.

Introduction. Malaria is the sixth leading cause of death worldwide. According to a WHO survey (2019-2020), the total number of malaria deaths is estimated to be 409000. Plasmodium falciparum and Plasmodium vivax are major malaria parasites, particularly in subtropical areas.

Materials and methods. In the present study, we used a transcriptome analysis of raw RNA sequence data to identify and characterize the differentially expressed genes in Plasmodium falciparum chloroquine-sensitive and chloroquine-resistant strains, as well as Plasmodium vivax primaquine sensitive and primaquine resistant strains. The raw RNA sequence data were obtained from the NCBI SRA database using the Accession IDs PRJNA308455, SRR14191963, and SRR332573.

Results and discussion. The sequence of raw RNA was quantified, mapped, and annotated. The total number of reads mapped to the reference genome for Plasmodium falciparum was found to be 45474448 and for Plasmodium vivax was 38226870. The Cufflinks-Cuffdiff tool was used to identify differentially expressed genes in Plasmodium falciparum and Plasmodium vivax sensitive and resistant strains. This differentially expressed gene was further annotated and plotted using the "Limma" package of Bioconductor. The PPI network was constructed in String Database and Cytoscape software. Pathway enrichment analysis of list differentially expressed gene performed using KEGG and GO tool.

Conclusion. In sensitive and resistant strains, comparative transcriptome analysis revealed differentially regulated gene expression patterns.

Introduction. Lactoferrin is a biologically active substance, a natural glycoprotein from the group of iron-containing proteins, transferrin. This article is devoted to a review of the literature data on the properties and prospects for the use of lactoferrin in medicine and veterinary medicine.

Text. The problem of widespread use of lactoferrin is the need to use a large volume of raw materials, the difficulty of extracting it from agricultural raw materials and subsequent purification. In this view, at present, it is very promising to use transgenic animals to obtain such a valuable compound in the required volume. Discovered in 1939 in cow's milk, lactoferrin exhibits a wide spectrum of biological activity, new properties of this protein are constantly being established. The most studied are the immunomodulatory effects, anti-inflammatory, antimicrobial, antiviral, antifungal activities of lactoferrin, and the search for the possibility of using this compound for the treatment and prevention of the new coronavirus infection SARS-CoV-2, as well as for the prevention of postCOVID complications, has begun. In recent years, the antitumor activity of lactoferrin has been actively studied, as well as the prospects for its use as a biomarker for early diagnosis of neurodegenerative diseases. Lactoferrin can play a special role in the delivery of drugs to target organs, as well as in the manufacture of functional food products and various drugs for both humans and animals.

Conclusion. Thus, the performed theoretical study and the data obtained on a wide spectrum of biological activity of lactoferrin confirm the prospects and expediency of the development of formulations and technology of drugs, functional food products, veterinary drugs and animal products based on lactoferrin.

Introduction. One of the most promising directions in the search for biologically active compounds is the molecular design of biologically active compounds containing a known pharmacoform fragment. In this article, phenylacetic acid derivatives are considered as a scaffold for the search for biologically active compounds. However, the phenylacetamide derivative is of particular interest, its fragment is included in the structure of the atenolol drug. Optimization of methods for the synthesis of N-acylphenylacetamides and N-acyl-β-ketoamides will expand the boundaries of molecular design and targeted synthesis of biologically active substances containing a phenylacetic acid fragment as a centroid.

Aim. Obtain N-acylphenylacetamides and N-acyl-β-ketoamides, optimize the synthesis and isolation methods, and establish the degree of manifestation of the psychotropic activity of the compounds.

Materials and methods. Obtaining the target N-acylphenylacetamides was carried out by the interaction of 2-phenylacetamide with carboxylic acid anhydrides under conditions of acid catalysis. The next stage of the synthesis was the preparation of N-acyl-β-ketoamides by the interaction of the synthesized N-acylphenylacetamides with carboxylic acid anhydrides in the proposed catalyst for boron trifluoride diacetate. The structure of the compounds was confirmed by IR, ¹H NMR spectrometry. The individuality and purity of the obtained compounds were monitored by thin layer chromatography. The study of the synthesized compounds on the central nervous system was carried out in the tests "Conditioned reflex of passive avoidance – CPAR", "Extrapolation escape (ETI)", "Morris water maze" and "Beam Walking".

Results and discussion. As a result of the research, N-acylphenylacetamides and N-acyl-β-ketoamides were synthesized. The essence of the optimization of the procedure for the synthesis of N-acylphenylacetamides is to replace chloric 65 % with concentrated sulfuric acid. The ¹H NMR spectra confirming the structures of the synthesized compounds revealed important characteristic features for N-acetyl-3-oxo-2- phenylpentanamide (VI) and N-acetyl-3-oxo-2-phenylhexanamide (VIII) containing a chiral center. The resulting substances have a pronounced effect on the central nervous system, their nootropic activity is to reduce the severity of sensorimotor disorders in animals. As a result of the study, the leading compounds were identified, superior to the effect of the reference drug piracetam.

Conclusion. The carried out research confirms the expediency of searching for highly effective and safe nootropic agents in the series of acylated derivatives of phenylacetic acid amide.

Introduction. Oncolytic virotherapy is one of the approaches in immunotherapy of solid brain tumors. Measles virus vaccine strains are prospective agents for the therapy of cancers such as neuroblastoma, mesothelioma, and glioblastoma multiforme. The hyperexpression of the CD46 and other receptors on the surface of malignant cells allows the measles virus to infect and lyse the tumor, thus inducing an immune response. However, widespread immunization of the population and the resistance of neoplasms to oncolysis present difficulties in clinical practice.

Text. This review covers approaches to modifying the measles virus genome in order to increase specificity of virotherapy, overcome existing immunity, and enhance the oncolytic effect. It was shown that expression of proinflammatory cytokines on viral particles leads to tumor regression in mice and triggers a T-cell response. Several approaches have been used to overcome virus-neutralizing antibodies: shielding viral particles, using host cells, and altering the epitope of the protein that enables entry of the virus into the cell. Furthermore, the insertion of reporter genes allows the infection of target cells to be monitored in vivo. A combination with the latest immunotherapies, such as immune checkpoint inhibitors, demonstrates synergistic effects, which suggests the successful use of combined approaches in the therapy of refractory tumors.

Conclusion. Measles virus attenuated strains appear to be an easy-to-modify and reliable platform for the therapy of solid brain tumors.

Introduction. When transferring the technology of cosmetic emulsion cream from laboratory conditions to semi-industrial equipment, it is necessary to determine the critical process parameters that will allow achieving results without losing the quality of the final product.

Aim. The aim of the study is to confirm the effectiveness of the developed technology for the production of emulsion cream under scaling conditions.

Materials and methods. As active substances were used badan thick-leaved extract dry, salicylic acid, dimethicone, menthol and octypyrox; emollients – grape seed oil, coconut oil, castor oil; emulsifiers and co-emulsifiers – distilled monoglycerides, emulsion wax, anhydrous lanolin, Cremophor A25; humidifier – glycerin; alkaline agent, pH regulator – triethanolamine; preservative – Euxil 9010; fragrance – essential oil of rosewood, solvent – purified water. Phase mixing and emulsification were carried out in a PRS AR 403 planetary mixer (ERWEKA GmbH, Germany), dosing into a sealed plastic container was carried on an FDS II AR 403 ointment dosing unit (ERWEKA GmbH, Germany). The study of the physicochemical and structural-mechanical properties of the cream was carried out in accordance with GOST 29188.2-2014 and GOST 29188.3-91.

Results and discussion. Under scaling conditions, 3 pilot series of cosmetic emulsion cream for the prevention of dry seborrhea of the scalp based of badan thick-leaved extract dry have been developed. The cream obtained both in the pilot and laboratory phases met all the requirements of the Technical Regulations of the Customs Union (TR CU) 009/2011 "On the safety of perfumery and cosmetic products", which confirms the reproducibility of the developed production technology. A 20-fold increase in loading did not affect the methods of introducing the components and their percentage. To determine the possibility of technology transfer from laboratory conditions to semi-industrial production conditions, the technological characteristics of the equipment were analyzed for the ability to carry out the required technological process, using the Ishikawa diagram, risks were identified and causal relationships of the production. The most important indicators of the technological process have been established – these are the temperature, the number of revolutions of the mixer and the mixing time.

Conclusion. On the semi-industrial equipment of the GMP training center, the technology of obtaining a cosmetic emulsion cream based on badan thick-leaved extract dry. A causal diagram (Ishikawa diagram) was compiled. Taking into account possible risks in the production of emulsion cream (number of revolutions of the mixer, stirring time, temperature) made it possible to obtain a stable product that meets all the requirements of TR CU 009/2011 "On the safety of perfumery and cosmetic products". The reproducibility of the technological process is shown.

Introduction. To reduce frequency of taking celecoxib dosage forms, as a highly effective drugs of the latest generation for the treatment of inflammatory diseases of the musculoskeletal system, it is advisable to develop pharmaceutical dosage form with modified release, which will reduce side effects and costs treatment.

Aim. The purpose of this study was to develop formulations of prolonged release celecoxib granules.

Materials and methods. Experiments were carried out with materials and equipments of the scientific laboratories of the company LEM pharma (Hama, Syria). The physico-chemical and technological properties of the experimental samples of granules and tablets of celecoxib were determined according to the methods of the American Pharmacopoeia USP 41 NF 36 edition.

Results and discussion. The choice of excipients, in particular, cellulosic polymers to control releasing celecoxib was carried out. The compositions of six model samples of celecoxib granules were proposed. The technological characteristics of the samples of granules (index Hausner, Carr ratio, Particle size distribution and moisture content) have been determined, using a dissolution test, their suitability for obtaining capsules and matrix tablets of prolonged release has been established.

Conclusion. The compositions of granules celecoxib with modified release are developed, which can be used to obtain capsules, as well as matrix tablets as the final pharmaceutical form.

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".

Introduction. The Laboratory for the development of dosage forms of the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a composition of an injectable liposomal dosage form based on soybean phosphatidylcholine, a hydrophobic analog of the hypothalamic hormone somatostatin − cyphetrylin, intended for the treatment of neuroendocrine tumors.

Aim. Determination of optimal technological conditions for the process of obtaining a liposomal dosage form of cyphetrylin.

Materials and methods. The study used the substance cyphetrylin synthesized in the of Chemical Synthesis Laboratory of the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation; soybean phosphatidylcholine S PC and polyethylene glycol-2000-distearoylphosphatidylethanolamine, produced by Lipoid GmbH (Germany); cholesterol ≥99 % (Sigma-Aldrich, Japan). For the preparation of phospholipid vesicles loaded with cyphetrylin and "empty", the methods of lipid film hydration with subsequent extrusion or homogenization of the dispersion of multi-layer liposomes were used. The obtained liposomal samples were evaluated by quality indicators − the effectiveness of the inclusion of cyphetrylin in vesicles, their average size and surface charge (zeta potential), the viscosity of the dispersion. To evaluate these characteristics, the methods of spectrophotometry, laser scattering spectroscopy, determination of the electrophoretic mobility of particles and viscometry were used.

Results and discussion. It was found that the most suitable organic solvent for obtaining a solution of cyphetrylin and lipid components of the dosage form is chloroform. The duration of the drying period of the lipid film under vacuum to remove the residual solvent is determined by the ratio of the volume of the distillation flask used and the mass of its loading its loading. At the same time, hydration off the lipid film with water for injection should be carried out under conditions of low-pressure and room temperature. To obtain a dispersion of single-layer cyphetrylin liposomes of the required size, an extrusion method using nylon and polycarbonate membranes with a filter pore diameter of 0.22 and 0.2 um, respectively, was chosen.

Conclusion. The optimal technological conditions for the process of obtaining a liposomal dosage form in the form of a dispersion of a hydrophobic analog of the hypothalamic hormone somatostatin − cyphetrylin are determined.

Introduction. Ivermectin is known as a veterinary agent with a wide spectrum of action against endo-and exoparasites of farm animals, which makes its use promising. Therefore, the possibility of creating prolonged parenteral dosage forms using polymer biodegradable carriers is currently being investigated. To carry out their quality control, a method of quantitative determination of the active substance is necessary. Most of the previously proposed methods are characterized by time-consuming sample preparation, complex composition of the mobile phase or a long analysis time, therefore, during the development of an injectable prolonged preparation of ivermectin based on polycaprolactone microparticles, a new method for the quantitative determination of ivermectin was proposed, which is simple and suitable for use in production.

Aim. Development of a method for the quantitative determination of ivermectin in the composition of polycaprolactone microparticles and its validation.

Materials and methods. Microparticles with ivermectin were used as the object of the study. The method of quantitative determination of ivermectin in the test sample was developed on a high-performance liquid chromatograph Dionex UltiMate 3000 (Thermo Fisher Scientific, USA), equipped with a diode-matrix detector.

Results and discussion. In this paper, various conditions for the quantitative determination of ivermectin in the composition of polymer microparticles are studied. Based on the obtained data and results, a method has been developed that has optimal sample preparation and analysis conditions.

Conclusion. As a result of the development, the conditions for the analysis were selected, which allow us to evaluate the quantitative content of ivermectin in the sample. The method was validated for the parameters specificity, analytical area, linearity, trueness, repeatability, intermediate precision.

Introduction. Scanning electron microscopy acts as a promising method of analysis, allowing to describe in detail the identification features of closely related plant species, as well as to conduct micro-roentgenstructural analysis of the sample in the selected area with high accuracy. The method is used to study the morphology of the surface and express determination of the composition of elements in various fields (physics, materials science, medicine, however, the use of the method of scanning/raster electron microscopy for the analysis of plant raw materials in pharmacy is limited.

Aim. The purpose of the study was to study species of the genus Persicaria Mill. using scanning electron microscopy.

Materials and methods. The objects of study were the Persicaria maculosa S.F. Gray, Persicaria hydropiper (L.) Delarbre, Persicaria tomentósa (Schrank) E.P. Bicknell, Persicaria mínor (Huds.) Opiz, Persicaria amphibia (L.) Delarbre, Persicaria amphibia var. terrestris (Leyss.) Munshi & Javeid, harvested during flowering in the Voronezh region. The study of samples by scanning electron microscopy was carried out on an electron microscope JSM-6510LV (Center for Collective Use of Voronezh State University).

Results and discussion. With the help of scanning electron microscopy, morphological and anatomical signs of leaf plates of six species of the genus Persicaria were investigated and new diagnostic signs were identified. As a result of micro-X-RAY analysis, the content of some elements (potassium, calcium and magnesium) was established in the objects of study.

Conclusion. For the first time to analyze the surface morphology of the leaf plate of species of the genus Persicaria Mill. the method of scanning electron microscopy is used. The features of the stomatal apparatus, trichomes and glands on the leaves of the studied species of Persicaria are clarified. With the help of micro-roentgenstructural analysis it was found, that a greater amount of magnesium is typical for the leaves of Persicaria mínor, calcium – for the leaves of Persicaria hydropiper, and potassium – for the leaves of Persicaria maculosa.

Introduction. Dodecyl(3,5-dimethyl-4-hydroxybenzyl)sulfide (T1) and bis-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl]sulfide (T2) are the collaborative development of Novosibirsk State Pedagogical University and Novosibirsk Research Institute of Antioxidants. It was revealed in several experiments and research works that these substances have antioxidant, anti-inflammatory, hepatoprotective, cytoprotective, haemorheological activities. These facts make the objects of study promising medicinal antioxidant drugs. Consequently it’s necessary for the future production quality control to have standards and analytical methods for substances analysis.

Aim. Impurities methods development and validation for the new biologically active substances T1 and T2.

Materials and methods. HPLC method with UV-detection on 278 nm was carried out for the determination of impurities in objects of study. HPLC analysis were performed on ZORBAX SB-C18 (5 μm, 150 × 4,6 mm) column with isocratic regimen and with use of the acetonitrile:water mixture (T1) or acetonitrile (T2) as a mobile phase.

Results and discussion. It was find out, that T1 has two unidentified impurities with concentration not more than 0,1 % during the shelf life. The chromatogramm of T2 has a peak of by-product of synthesis T2 – bis-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl]disulfide (T2-DS). Biologically safety of T2-DS was demonstrated in the previous works and the concentration of T2-DS was established to be not more, than 2,5 %. Furthermore, there was the one more unidentified impurity with concentration less, than 0,1 % on the chromatogram of T2. The developed HPLC methods were validated on characteristics «specificity», «linearity», «precision», «limit of quantification», «accuracy», «range».

Conclusion. Methods for the determination of impurities in T1 and T2 were validated on the listed parameters. All the results meet the acceptance criteria: peaks on the chromatogramms are clearly separated; the correlation coefficients (r) are not more, than 0,980; accuracy was proved by linearity parameters; the value of the relative standard deviation is less, than 5 %; the intermediate precision for the both methods was proved by Fisher’s criterion and Student’s t-test.

Introduction. The roots of one-year-old sunflower (Helianthus annuus L.) are mainly wastes of agricultural enterprises when cultivating this crop. At the same time, they differ in a rich chemical composition and contain water-soluble polysaccharides, the base of which is inulin.

Aim. The aim of this study is to select optimal parameters of ultrasonic extraction of water-soluble polysaccharides from sunflower roots of oneyear old based on regression analysis.

Materials and methods. For the experiment, raw materials purchased from one of the pharmacies in the city of Voronezh were used. A sample of raw materials (1.0 grams) was placed in an ultrasonic bath Grad 40-35, which allows maintaining the necessary temperature and frequency of ultrasound with a given duration of time. Then, 10 (15 or 20) ml of purified water purified from impurities at a temperature of 60 °C to 80 °C was measured with a measuring flask and extracted from 10 to 20 minutes with a multiplicity of 1 to 3, and after each of the multiple studies, the same raw material was further filtered with a new solvent.

Results and discussion. The initial conditions and the data obtained during the experiments made it possible to present the regression model in the form of a linear multiple regression equation, which can be used with sufficient accuracy in prediction and analysis. The adequacy of the model was confirmed by testing hypotheses against Pearson's χ² criterion. The correlation coefficient derived from the values of the regression coefficient and the mean square deviation was used in determining the tightness of the overall relationship between the source and the obtained data. In addition, a detailed study of a sample of those variables whose priority was not clearly expressed was carried out by processing when fixing their values.

Conclusion. The most important conditions for extraction of the roots of sunflower of a one-year old should be considered: extraction temperature equal to 80 °C; extraction multiplicity equal to 3; an ultrasound frequency of 35 kHz; Note here that raw material grinding can vary from 0.5 mm to 2 mm, extraction time can range from 15 min to 20 min, ratio of raw material and extractant can vary from 1 g per 10 ml to 1 g per 15 ml.

Introduction. Sea buckthorn – Hippophaё rhamnoides is a perennial shrub, the fruits of which are a source of carotenoids and are harvested on an industrial scale to obtain a number of drugs. Recently, not only fruits, but also other parts of the plant, such as buds, leaves, shoots and bark, are of increasing interest. It is known that sea buckthorn leaves are rich in compounds such as tannins, polyunsaturated fatty acids and vitamins (C and E). The rich composition of biologically active substances with a sufficient content of components allows us to consider leaves as a new type of medicinal plant material for the further development of various preparations based on them. In addition, the leaves are an annually renewable raw material and it is possible to harvest them on an industrial scale, since this valuable medicinal plant is cultivated everywhere in Russia. Data on the microscopic characteristics of the fruits of sea buckthorn are described in detail in the scientific literature, which cannot be said about the leaves. The scientific literature also does not describe the features of the luminescence of the tissues of the leaves of the sea buckthorn.

Aim. The aim of this work was to study the possibility of using the luminescent and stereomicroscopic methods of analysis to determine the main morphological features of the leaves of the sea buckthorn.

Materials and methods. Dried whole leaves of a plant of the genus Hippophaës collected in the Voronezh region were used as the object of the study. The study of microdiagnostic signs was carried out according to the State Pharmacopoeia of the XIV RF GPA.1.5.3.0003.15 «Technique of microscopic and microchemical examination of medicinal plants and herbal medicinal products». A stereomicroscopic study was carried out using a Biomed 2 microscope. The luminescence of the tissues of the sea buckthorn leaves was investigated using a luminescent microscope of the Miсromed 3 LUM brand.

Results and discussion. Stereomicroscopic analysis of sea buckthorn leaves was carried out. High-resolution volumetric images were obtained in a short period of time. It was found that the characteristic microscopic features of the leaves are the presence of a large number of corymbose hairs along the upper and corymbose-stellate along the lower surfaces, including the vein and petiole (from colorless to white, yellow and dark brown). Single simple stellate hairs are rare. When removing the layer of hairs, the spongy structure of the epidermis of the leaf is visible. The carried out luminescent analysis made it possible to reveal the features of the luminescence of the tissues of the leaves of the sea buckthorn. Diagnostic luminescent features include: the most pronounced yellow glow is observed for the cells of the base of the corymbose hair; the plates that make up the corymbose hairs do not have bright fluorescence; stellate hairs do not have a glow; pronounced yellow-green fluorescence is characteristic of the leaf vein.

Conclusion. For the first time, stereomicroscopic and luminescent analyzes of sea buckthorn leaves were carried out and the main morphological features of this type of medicinal plant material and their biometric characteristics were established. The carried out luminescent analysis made it possible to reveal the features of the luminescence of the tissues of the leaves of the sea buckthorn.

Introduction. Orthilia secunda (L.) House, Sedum quadrifidum Pall., Rhodiola heterodonta (Hook. f. & Thomson) Boriss. are actively used in folk medicine for the treatment of gynecological pathologies, however, the raw materials of these species are registered as dietary supplements, since there are no data from complex phytochemical analysis and standardization criteria. Since macro- and microelements are of great importance for the therapy and prevention of gynecological diseases, the determination of the elemental composition of medicinal plant raw materials is an important stage in a comprehensive phytochemical research of these plants with the purpose of introducing them into official medicine.

Aim. Analysis of the macro- and microelement composition of the rhizomes and roots of Sedum quadrifidum, Rhodiola heterodonta in comparison with Sedum roseum and analysis of the mineral composition of the herb Orthilia secunda from three harvesting sites.

Materials and methods. For research purposes, the grass of Orthilia secunda (L.) House was harvested in three phytocenotic zones – the southern part of Kazakhstan (July 2018), the Tyumen region (harvesting July-August 2019) and the Perm region (July 2019). Rhizomes and roots of Sedum rosea were harvested in the SPCPU in the village Lembolovo, Leningrad region (2019). Medicinal plant raw material of Sedum quadrifidum was purchased in a pharmacy chain in St. Petersburg, the place and time of procurement according to the information on the package is Altai, March 2019. Rhodiola heterodonta was harvested in Tajikistan (March 2018). The analysis was carried out by inductively coupled plasma atomic emission spectrometry (AES) on an Optima 8000 spectrometer (Perkin Elmer, USA) with preliminary sample preparation by the wet mineralization method in accordance with the recommendations of the State Foundation of the Russian Federation XIV OFS1.2.1.1.0004.15 and OFS 1.5. 3.0009.15 on the basis of the Center for Collective Use "Analytical Center". Statistical processing of the results was carried out using the Microsoft Excel program according to GM.1.1.0013.15.

Results and discussion. According to the results of the experiment, it was found that Sedum quadrifidum contains a greater amount of sodium, iron, aluminum, and manganese in comparison with other types of Rhodiols, and the content of manganese is 3 times higher than in the Sedum rosea, and 4.9 times more than in the Rhodiola heterodonta. Rhodiola heterodonta is distinguished by a high content of calcium, potassium, and magnesium. The results of studying the elemental composition of Orthilia herb showed that the harvesting region does not significantly affect the mineral profile of the plant. However, in Orthilia secunda (L.) House harvested in Kazakhstan, a high content of barium is noted, iron, magnesium, manganese, and zinc also slightly prevail, which may be associated with technogenic soil pollution in this region. A significant content of manganese was noted in the herb of orthilia (1801.50 mg/kg), which is higher than in the raw material of rhodiola, which belongs to manganophiles. This makes it possible to classify ortilia as a plant that selectively accumulates manganese, and to position it as an indicator of soils rich in salts of this element. The results of statistical processing made it possible to establish the confidence interval of the mean value, which characterizes the uncertainty of the analysis results and the RSD, which characterizes the precision of the results obtained.

Conclusion. Sedum quadrifidum accumulates the maximum numberof elements in comparison with Sedum roseum. Barium and strontium are the major microelements of the Rhodiola. Sedum quadrifidum is marketed as a manganophil. In the herb of Orthilia, manganese is significantly prevalent, which makes it possible to classify Orthilia as a manganophilous species. The total content of copper, iron, zinc and calcium in the raw material of Rhodiola heterodonta and Orthilia secunda herb confirms the prospects for the development of phytopreparations based on these species of raw materials for the treatment and prevention of gynecological pathologies.

Introduction. Allaforte® (JSC "Pharmcenter VILAR", Russia) is an antiarrhythmic long-acting drug. The dosage form of the drug Allaforte® provides a decrease in the frequency of taking the drug and also reduces the risk of side effects. It is relevant when taking antiarrhythmic drugs of the IC class. However, the pharmacokinetics of this drug has not been studied on humans. Therefore, it is important to fully study the pharmacokinetics to ensure the maximum efficacy and safety of arrhythmia therapy.

Aim. The aim is pharmacokinetics study of long-acting antiarrhythmic drug Allaforte® (JSC "Pharmcenter VILAR", Russia), 25 mg.

Materials and methods. Concentration of lappaconitine and its active metabolite N-desacetyllappaconitine in human plasma determinates by high performance liquid chromatography with tandem mass-spectrometry. Pharmacokinetic parameters calculated by R Project 3.5.1 software (package «bear», version 2.8.3-2), originally created by Hsin-ya Lee and Yung-jin Lee, Taiwan.

Results and discussion. Pharmacokinetic parameters of lappaconitine and N-desacetyllappaconitine were calculated. Averaged pharmacokinetic profiles (in linear and semi-log scale) of lappaconitine and N-desacetyllappaconitine after single administration under fasting were built. The means of the maximum concentrations (C_max) determined in the blood plasma of volunteers after single administration Allaforte® are 5.09 ± 4.07 ng/ml for lappaconitine and 11.66 ± 6.21 ng/ml for N-deacetyllappaconitine (Mean ± SD). The peak time of the maximum concentrations (T_max) is 4.43 ± 3.54 hours for lappaconitine and 4.04 ± 2.18 hours for N-deacetyllappaconitine. The means of the areas under the curve plasma concentration – time from 0 to 48 hours (AUC_0-t) and under the curve plasma concentration–time from zero to infinity (AUC_0-∞) of Allaforte® is 42.96 ± 34.48 ng ∙ h/ml and 71.24 ± 43.20 ng ∙ h/ml for lappaconitine; 167.42 ± 114.41 ng ∙ h/ml and 189.42 ± 115.20 ng ∙ h/ml for N-deacetyllappaconitine. Allaforte® was eliminated from blood plasma with means of terminal half-life (T_1/2) 8.45 ± 5.10 hours for lappaconitine and 9.04 ± 2.57 hours for N-deacetyllappaconitine.

Conclusion. Pharmacokinetics study of long-acting antiarrhythmic drug Allaforte® (JSC "Pharmcenter VILAR", Russia) after single administration was researched. Results of the study allows to conduct an effective therapy of arrhythmia by study drug and minimize side effects.

Introduction. Good Manufacturing Practice (GMP) requires drug manufacturers to apply risk management principles in their operations. One of the main risks to the quality and safety of pharmaceuticals is cross-contamination. The introduction of a systematic approach to contamination risk management requires manufacturers to make a comprehensive assessment of both production processes and the organization of production sites (premises, equipment, systems, etc.). Therefore, the transition to the current GMP requirements for operating production sites may require significantly higher financial and labor costs than for projected production facilities.

Aim. Development of a scientifically based program and methodology for cross-contamination risk management for existing pharmaceutical industries, taking into account compliance with the harmonized GMP requirements of the Russian Federation and the EAEU and world practice.

Materials and methods. In the course of the study, methods of risk management, analysis and systematization of data and a process approach were used.

Results and discussion. The key aspects of the organization of the co-manufacturing of medicines are outlined. A step-by-step approach to risk management, involving a preliminary assessment of the conformity of a production organization with GMP requirements is described. The proposed scheme is aimed at ensuring the continuous functioning of the cross-contamination risk management process.

Conclusion. The presented risk management methodology aims to conduct a proper assessment of the risks of cross-contamination for multiproduct pharmaceutical enterprises. This technique allows to identify areas that need improvement to ensure compliance of manufacturing sites with GMP requirements, which ultimately contributes to improving the quality of medicines.

Introduction. An important task for pharmaceutical manufacturers is to bring high quality, effective and safe medicines to the market. In the event that the country's resources are not enough, drugs that have been successfully registered in other countries come to the rescue.

Aim. To study the possibilities and advantages of the procedure of mutual recognition of registration medicinal products as a potential for the development of domestic producers.

Materials and methods. The materials of the study were available publications in peer-reviewed journals on thematic queries based on keywords of the selected topic, official websites, regulatory legal acts, regulating the procedure for registering medicinal products in the EU and the Russian Federation.

Results and discussion. New approaches to registration within the framework of the Eurasian Economic Union (using the example of the mutual recognition procedure) are considered from the perspective of new opportunities and emerging problems for domestic manufacturers of generic drugs. A comparative analysis of the mutual recognition procedure and the national procedure for registration of medicinal products revealed a number of advantages for domestic manufacturers, favoring the introduction of medicinal products into circulation on the territory of the EAEU.

Conclusion. The review of the process of harmonization of the registration practice of medicinal products in the EAEU speaks of the prospects of using the mutual recognition procedure for developing the potential of domestic manufacturers and facilitating access to effective and safe drugs.

Introduction. The use of highly active substances of various origins in the pharmaceutical industry exposes employees working directly with active pharmaceutical substances (APS) in manufacturing facilities to risks. Although pharmaceutical companies follow occupational safety requirements, such as the use of personal protective equipment (PPE), the manipulation of highly toxic substances in specially dedicated indoor facilities, etc., the impact of risk factors on the health of workers must be regularly assessed and monitored. Therefore, hygienic monitoring of working area air is obligatory in activity of pharmaceutical enterprises. A range of normative documents (orders, State standards, methodological guidelines, manuals) are currently in force in the Russian Federation defining uniform requirements for the organization and monitoring of working area air pollution by particulates. At the same time, the development of appropriate adjusted methodologies for determining the content of a specific substance in working area air is a mandatory requirement for all manufacturing enterprise by legislation.

Text. The article provides a review of the Russian regulatory framework and relevant literature sources relating to the order of organization and performance of hygienic monitoring of working area air, including foreign ones. On the basis of a comparative analysis of the aforementioned literature completed in order to reveal common provisions, the comprehensive methodology for the monitoring of the content of harmful substances in the working area air at pharmaceutical enterprises is described.

Conclusion. As a result of a comparative analysis of the literature reviewed, a detailed comprehensive methodology for the monitoring of the content of harmful substances in the working area air is presented, including a description of the equipment and materials required for sampling, sampling strategies, recommendations for monitoring protocols, procedures for storage and transport of samples, and procedure for sample analysis. This article may serve as a possible reference for pharmaceutical enterprises to develop individual methodologies for determining the concentration of a specific substances in working area air.