The summer event was devoted to the discussion of certain aspects of the development, research and registration of biotechnological drugs. During the conference, we have discussed preclinical, clinical research, production of various groups of biotechnological drugs, including heparins, monoclonal antibodies, peptide drugs. The organizers of the conference are the LLC "Center of Pharmaceutical Analytics" and the scientific and production journal "Drug development & registration".

The third part presents the memoirs of V. N. Ipatiev about his trips to Germany, France, England, Belgium and other European countries in order to meet with the former owners of the plants to organize their obtaining concessions and purchase licenses, for the use in new schemes and methods for obtaining chemical products at refurbished facilities. In addition, VN Ipatieva describes her participation in the work on establishing the synthesis of asphyxiating gases, the domestic gas mask and organizing the work of the Dobrokhim public organization.

An important problem for pharmaceutical and toxicological laboratories is quick and accurate determination of mixtures of active pharmaceutical ingredients in various samples, including blood samples. This article shows the simultaneous quantitative analysis and identification of two common pharmaceutical ingredients (paracetamol and ibuprofen) on a SCION LC 6000 liquid chromatograph with a diode array detector. As a result of the experiment, it was shown that with the help of a diode-array detector with multi-wavelength function, it is possible to determine both substances in one injection. Excellent linearity and repeatability of the SCION HPLC-DAD was demonstrated with low RSD values and high R² values.

Biotechno group of companies’ experts – Maxim Benevolensky (Technical director) and Artem Nikulin (Chief of projects) – share their expertise in the topic of technological equipment choice which is usually made at the stage of biopharmaceutical production concept project. The experts told us about criteria that must be taken into account while choosing between stainless steel and single-use solution. They also compared economical efficiency of using different solutions for different products and then shared BIOTECHNO's foreign colleagues' experience in this area. In the end of our interview Maxim and Artem mentioned some barriers that exist when using stainless steel solutions and the ways to overcome these barriers.

A two-day rich business program, round tables and master classes are waiting for you. During the event, we will discuss issues of pharmaceutical development, research, production of original and generic drugs, as well as regulatory aspects of the current legislation of the EAEU.

On September 7–8, the VII GMP Conference with international participation will be held in Irkutsk. The organizers of the conference are the Ministry of Industry and Trade, the Federal State Institution «State Institute of Drugs and Good Practices». The operator is S-Group communication center.

From September 27 to 30, the science city of Koltsovo, Novosibirsk Region, will host the OpenBio platform for open communications in the field of virology, biotechnology, and biopharmaceutics for the 9th time. The OpenBio program will include a three-day conference of young scientists, an exhibition of achievements of biotechnology companies and a scientific and business forum with discussions on longevity, the development of medicines and reagents, the fighting of age-related diseases, preventing the spread of HIV infection, import substitution and the prospects for investing in science-intensive business in modern realities.

Introduction. The use of biologically active compounds of Baikal skullcap (Scutellaria baicalensis Georgi) becomes especially important under pandemic conditions. The plant's value becomes the cause of overexploitation of the skullcap subterranean parts, which leads to the reduction of the population distribution range and inappropriate conditions of collection and harvesting. To prevent the extinction hazard of the species, in vitro cultivation of the plant's cells becomes a promising technology. This opens up the prospect of studying the physiology and biochemistry of plant cells, regulating the direction of valuable secondary metabolites synthesis and creating medicines without interfering with the natural habitat. Modern technologies provide opportunities to automate cell cultivation in order to minimize human involvement in the process. However, cultivation of plant cells is a probabilistic process that is influenced by a range of factors. The use of risk management tools will reduce the number of unintended consequences leading to dangerous and critical cell culture conditions.

Aim. Risk analysis resulting from in vitro cultivation of Baikal skullcap (Scutellaria baicalensis Georgi).

Materials and methods. The object of the study was suspension cultures of Scutellaria baicalensis obtained from loose plant callus. Suspensions of Scutellaria baicalensis cells were grown in 250 ml flat-bottomed conical flasks under conditions of constant mixing on a shaker (rotation speed 100 rpm). The subculture cycle was 21 days. For microscopy of cell biomass, we used 0.1 % neutral red (NK) and 0,025 % Evans blue (EG) solution. Process risks were assessed using a cause-and-effect diagram (Ishikawa diagram).

Results and discussion. It was found that the cells in the suspension cultures of skullcap were characterized by an elongated oval shape. Primary suspensions were distinguished by the presence of predominantly parenchymal cells (70 ± 2,0 %). A large aggregation was observed in the primary suspensions. The diameter of the aggregates reached about 8–15 mm. The growth properties of Baikal skullcap suspension depended on the density of the inoculum. As the amount of transplanted biomass decreased, cells showed a tendency to destruction. The results indicated the need for risk analysis of the laboratory technology of Baikal skullcap suspension cultivation. Five most important factors in plant cell cultivation were identified: callus quality, quality of prepared liquid nutrient medium, equipment serviceability and suitability, operator actions, and suitability of cell culture technology and biomass viability index sampling.

Conclusion. An algorithm for analyzing the security of a Baikal skullcap suspension culture is proposed. The risk assessment can be used to make a conclusion about the probability of undesirable effects and their impact on the process. Risk management tools provide the basis for modernization of the available technology and automatic outfitting of the process.

Introduction. Dyslipidemia treatment in many cases requires carefully selected combination of lipid-lowering drugs including bile acid sequestrants. A promising compound is L-rhamnopyranosyl-6-O-methyl-galacturonan (L-RAG), a polysaccharide obtained from the birch leaves (Betula pendula L.).

Aim. To evaluate the lipid-lowering activity of L-RAG administered in combination with the HMG-CoA reductase inhibitor rosuvastatin or the cholesterol absorption inhibitor ezetimibe.

Materials and methods. Hyperlipidemia in hamsters was reproduced by synthetic diet supplemented with 0.3 % cholesterol and 11 % coconut oil (HFCD). At the end of the experiment the levels of triacylglycerols (TAG), bile acids, total cholesterol (TC), cholesterol of low-density lipoproteins (LDL-C) and high-density lipoproteins (HDL-C) were determined in the blood serum using Chronolab Systems S. L. enzymatic kits (Spain), and atherogenic index (AI) was calculated.

Results and discussion. L-RAG demonstrates a lipid-lowering effect in a model of diet-induced hyperlipidemia in hamsters. The decrease in the TC level was mainly caused by a decrease in the content of cholesterol in the atherogenic LDL fraction, which led to a decrease in AI. The use of rosuvastatin and ezetimibe in combination with L-RAG leads to a better lipid-lowering effect. The additive effect of the polysaccharide is mainly due to a decrease in the level of bile acids in the blood serum, which indicates its ability to absorb them in the intestinal lumen and interrupt enterohepatic circulation, acting like bile acid sequestrants.

Conclusion. It was shown that administration of L-RAG together with ezetimibe or rosuvastatin led to a better decrease in the TC, TAG, LDL-C levels than with polysaccharide monotherapy or comparison drugs alone. The obtained data substantiate the prospects of using L-RAG in the complex therapy of hyperlipidemia.

Introduction. Macrophages occupy a special place in the formation and coordination of the immune response, their population is characterized by heterogeneity, however, two main types are distinguished among them: pro-inflammatory (classically activated) macrophages M1, which are activated by interferon-γ (IFN-γ) or lipopolysaccharide (LPS) of bacteria, produce pro-inflammatory cytokines, nitric oxide (NO) and initiate an immune response, and anti-inflammatory (alternatively activated) macrophages M2, which are activated by such cytokines as interleukin 1 (IL-1), IL-10 or IL-13 and are associated with suppression of the immune response and tissue healing. The proinflammatory properties of macrophages are most often associated with the activation of an intracellular signaling cascade with the participation of the IKK-2 kinase complex and nuclear factor-κB (NF-κB), which is the most important signal transduction molecule. Previously, the authors showed that humic acids (HA) of peat cause the appearance of pro-inflammatory properties in macrophages; however, the intracellular mechanisms of such activation have not been studied.

Aim. Study of the contribution of the intracellular signaling cascade IKK-2/NF-κB to the activation of pro-inflammatory properties of macrophages by humic acids of peat.

Materials and methods. The studies were carried out using cultural methods and western blotting.

Results and discussion. It was shown that the addition of the IKK-2 inhibitor to the macrophage culture reduced the ability of HA to stimulate the production of nitric oxide by the cells. Western blotting revealed that after 30 minutes simultaneous incubation of HA with macrophages, the content of the NF-κB p65 molecule in the cells increased, after 60 minutes it decreased to the values of intact control, and after 17 hours it decreased 3 times compared to the control level. However, the IKK-2 inhibitor after a 30-minutes incubation did not have a blocking effect on the IKK kinase, whereas in an hour of the co-incubation of the cells with the inhibitor and substances, a decrease in the level of NF-κB p65 was observed. This trend continued in 17 hours.

Conclusion. The stimulating effect of peat humic acids on macrophages is realized, among other things, due to the activation of the IKK-2 kinase complex with further release of the p65 subunit of the NF-κB molecule. The dependence of the degree of NF-κB activation on the period of interaction of the cell with activating agents is traced. HA start the intracellular signaling cascade of the nuclear factor NF-κB already within the first 30 minutes.

Introduction. The article presents the results of studying the antithrombotic activity of a novel drug, a soluble guanylate cyclase stimulator (codename – GRS), in experimental models of arterial and venous thrombosis and thromboembolism.

Aim. Study the antithrombotic action of GRS compound in comparison with clopidogrel and rivaroxaban in the following models: arterial thrombosis induced by iron chloride application to carotid artery wall in rats; thromboembolism induced by intravenous administration of thrombin solution in mice; venous thrombosis induced by the ligature of inferior vena cava in rats.

Materials and methods. Arterial thrombosis was modelled in rats by applying a pad soaked in iron chloride (FeCl₃) to the carotid artery, GRS compound was administered orally in median effective dose of 10 mg/kg once 3 hours before pad application. Blood flow in carotid arteries and blood clot mass were registered. Thromboembolism was induced in mice by intravenous administration of thrombin solution, GRS in dose 10 mg/kg or the reference drug clopidogrel were administered once orally daily for 3 days. Animal mortality, survival time and blood clot size were registered. Venous thrombosis was induced in rats by the ligature of inferior vena cava below renal veins, GRS in dose 10 mg/kg, reference drug rivaroxaban in 5 mg/kg dose or their combination in these doses were administered once orally 1 hour before vein ligature. The mass of dry and wet blood clots was registered.

Results and discussion. In arterial thrombosis model GRS compound in 10 mg/kg, administered 3 hours before iron chloride application, increased the time to blood flow cessation in the carotid artery by 35 % and reduced the frequency of complete artery occlusion by 2 times compared to the control group (р < 0.05). 60 min after arterial thrombosis modelling complete occlusion was observed in 28 % of animals in GRS group and in 75 % of control animals, while after 24 hours the occlusion was observed in 14 % of animals in GRS group and in 50 % of control group animals (p < 0.05). In thrombin-induced thromboembolism model in mice GRS did not reduce the size of blood clots in pulmonary vessels, while clopidogrel reduced it by 48 %. In GRS group 80 % of animals died of thrombosis, compared to 30 % in clopidogrel group and 90 % in the control group. In ligature-induced venous thrombosis in rats GRS after single oral administration reduced the mass of dry blood clot, being as potent as rivaroxaban. Combined administration of GRS and rivaroxaban did not enhance their antithrombotic action.

Conclusion. GRS after single oral administration in 10 mg/kg dose had potent antithrombotic action in models of arterial and venous thrombosis in rats, while not preventing pulmonary vessel thrombosis in mice after thrombin administration. Therapeutic action of GRS in experimental venous thrombosis was as potent as that of rivaroxaban. Antithrombotic action of GRS compound results not only from its antiplatelet action, but also from the alleviation of endothelial dysfunction in arteries and veins.

Introduction. Natural deep eutectic solvents (DESs) are promising extractants for many biologically active substances from plant raw materials. They are biodegradable, safe, stable, their production is affordable and easily feasible, and the extraction efficiency is comparable to known organic solvents. In this regard, interest in deep eutectic solvents has been steadily growing in recent years, and they are being used in various fields of chemistry, pharmaceuticals and the food industry.

Aim. The purpose of this work was to study the possibility of extracting flavonoids from plant raw materials using deep eutectic solvents, as well as to compare the efficiency of their extraction with traditional solvents.

Materials and methods. The extraction of flavonoids was carried out from the collection of a plant composition consisting of the herb of motherwort cordial (common motherwort) (Leonurus cardiaca L.), the herb of St. John's wort (Hypericum perforatum L.), the herb of lemon balm (Melissa officinalis L.) and the herb of creeping thyme (thyme) (Thymus serpyllum L.) in a ratio of 4 : 2.5 : 2.5 : 1, crushed to a particle size of 2–3 mm. 21 eutectic solvents based on betaine hydrochloride and choline bitartrate as hydrogen bond acceptors were used as extractants.

Results and discussion. The extracting ability of 21 experimental compositions of DESs was studied. The influence of the water content in the composition of DES, as well as the effect of temperature on the extraction process, has been studied. Quantitative determination of flavonoids in terms of rutin was carried out by differential spectrophotometry at a wavelength of 410 ± 2 nm. The maximum yield of flavonoids was achieved using a 40 % aqueous solution of DES based on betaine hydrochloride and propylene glycol in a molar ratio of 1 : 3 at 60 °C.

Conclusion. The recovery ability of the obtained DES is comparable in efficiency and even slightly exceeds that of the classic extractant for the investigated composition – 70 % ethyl alcohol. Further development and optimization of the process of using DESs is a promising direction for the development of chemistry and pharmaceutical technology.

Introduction. The low solubility of active pharmaceutical ingredients (APIs) in the physiological pH range of the intestinal tract can adversely affect their absorption and bioavailability. Various methods of increasing the solubility of APIs have been proposed in recent decades. Among them there are preparation of solid dispersions, micronization, solubilization and other methods, including ones based on the amorphization of the crystalline substances, such as, spray drying, hot melt extrusion, absorption on mesoporous carriers such as magnesium aluminosilicate, silica, etc.

Aim. Study the technological methods effect on dissolution at physiological temperature and pH range of practically insoluble API efavirenz amorphized by absorption on mesoporous carriers.

Materials and methods. Efavirenz form І (EFA) (LLC "AMEDART", Russia, batch 010520). Efavirenz reference standard (USP № R09740). Mesoporous carriers (MC): Silica – Syloid^® 244FP (244), Syloid^® XDP 3150 (3150) (W.R. Grace&Co.-Conn, USA); FujiSil^™ (FSL) (Fuji Chemical Industries Co., Ltd., Japan); Aeroperl^® 300 (APL) (Evonik, Germany); Parteck^® SLC (SLC) (Merck Millipore, USA); Synthetic magnesium aluminometasilicate – Neusilin^® US2 (US2), Neusilin^® UFL (UFL) (Fuji Chemical Industry Co., Ltd., Japan). The API absorption on MC was performed via solvent wetting and hot melt extrusion methods.

Results and discussion. The dissolution increases in the MC series as the following: SLC > FSL > UFL = US2 > 244 = 3150. The data are consistent with an increase in the surface area and a decrease in the pore size of MC. The crystalline state of the system API efavirenz-Aeroperl^® is caused by the largest pore size. It is obvious according to the data that the solvent wetting method gives better results in comparison with the hot melt extrusion as the method of obtaining X-ray amorphous systems API efavirenz-MC.

Conclusion. Solvent wetting technology is recommended for increasing the dissolution of practically insoluble APIs. The preferable mesoporous carriers are silica Parteck^® SLC or synthetic magnesium aluminometasilicate Neusilin^® US2.

Introduction. Currently, despite the achievements in the synthesis of chemical substances, there is a tendency to expand the use of herbal medicines, the use of which is justified by the relative safety and breadth of pharmacological activity. One of the promising sources of biologically active substances are plants of the genus Goldenrod, which has more than 20 plant species. Despite the active botanical and pharmacological study of plants of the genus Solidago, there is insufficient scientific data to date. In addition, the extraction of extracts based on Solidago grass has not been studied in detail, which determines the relevance of the study of representatives of this genus in the technological aspect.

Aim. Determination of optimal conditions for the extraction of biologically active substances from the grass of Solidago virgaurea.

Materials and methods. The herb Solidago virgaurea, collected during the flowering period, was used as the studied plant raw material. Drying of raw materials was carried out in a natural shadow way. The amount of extractive substances in the aqueous extracts of Solidago grass was determined by the pharmacopoeia method (OFS.1.5.3.0006.15 Determination of the content of extractive substances in medicinal plant raw materials and medicinal plant preparations). Biologically active compounds from dried and crushed raw materials were extracted with 40 %, 60 %, 80 % and 96 % ethyl alcohol solution. The quantitative content of biologically active substances in extracts of the herb Solidago virgaurea was determined by the dry residue. The percentage of saponins in the studied plant raw materials was determined in terms of oleanolic acid by direct spectrophotometry based on the reaction with sulfuric acid.

Results and discussion. The issues of studying the factors affecting the quality of extraction of saponins of Solidago grass are highlighted. The influence of the degree of grinding of raw materials, the mode of infusion and the type of extractant on the completeness of saponin yield has been studied. According to the results of the study of the extraction conditions of biologically active compounds of aqueous extracts of Solidago virgaurea grass, it was revealed that the maximum amount of biologically active substances was obtained in extracts prepared on the basis of grass crushed to a size of 2 mm by infusing in a water bath for 30 minutes. It was found that the quantitative content of saponins in Solidago virgaurea grass is 9.8 ± 1.2 %.

Conclusion. Based on the conducted research, the most rational technology of water extraction based on the herb Solidago virgaurea has been identified: the degree of grinding of raw materials is 2 mm; as an extractant, 60 % ethanol is the most optimal for saponins; the infusion mode is 30 minutes in a boiling water bath. According to the obtained results of quantitative analysis, it was found that the total saponin content in the grass of Solidago is 9.8 ± 1.2 %, which emphasizes the relevance of more detailed studies of this plant raw material from the standpoint of quantitative determination of biologically active substances and determination of a possible spectrum of pharmacological properties.

Introduction. Due to the discovery of antibodies (Ab) targeting molecule with high specificity to the ligand, the "magic bullet" concept has been successfully implemented with various immunoconjugated drugs. Since 1980, Ab conjugates with liposomes, i.e., immunoliposomes (ILs), have been widely investigated to improve the specificity and efficacy of drug therapy. This review is devoted to the characteristic of the basic structural units of ILs on the basis of data analysis of original and review articles on the topic from PubMed, ResearchGate and CyberLeninck databases.

Text. ILs are liposomes to which Ab, their fragments or other ligands are usually attached by a special linker. ILs are used to deliver antitumor, cardiovascular, antiviral, antiprotozoal drugs, genetic material, imaging molecules, etc. ILs can be derived from various phospholipids of both natural and synthetic origin, charged or neutral. The most widely used phospholipids in immunoliposomal construction are phosphatidylcholines. To increase the mechanical stability of the bilayer, sterols are introduced into the lipid composition. For selective liposome delivery, targeting ligands must be attached to the nanocarrier via the spacer arm of the PEG. Several types of end-group functionalized lipopolymers are used for this purpose, usually of the general formula X-PEG-LI, where X represents a fragment containing a reactive functional group − maleimide, biotin, cyanur, amine, etc. These lipid PEG-conjugates exhibit excellent amphiphilic properties and offer excellent advantages for the modification, formulation, and delivery of various drugs. The Ab used should enhance the accumulation of the liposomal drug in the target areas with minimal cross-reactivity with healthy tissues. Ready-made drugs based on monoclonal Ab, such as trastuzumab, cetuximab, panitumumumab, bevacizumab; commercial Ab intended for research purposes, and laboratory synthesized Ab and their fragments are used in the preparation of ILs. Ab can be attached to liposomes by two main methods: direct covalent conjugation and postinsertion.

Conclusion. The results of this study allowed us to summarize the variety of literature data on the composition of ILs and the possibility of using auxiliary components to achieve the goal in the development of the drug.

Introduction. Orodispersible dosage forms are a very promising direction in the development of dosage forms. Such dosage forms are designed for both systemic and local action of the active pharmaceutical ingredients that make up their composition. Active pharmaceutical ingredients from orodispersible forms enter directly into the systemic circulation, bypassing the "first pass effect".

Aim. Development of orodispersible tablets based on the Eudragit^® EPO/ibuprofen polymer-drug complex and evaluation of ibuprofen release from the resulting system.

Materials and methods. Samples of the polymer-drug complex (PDC) were obtained with different ratios of EPO and ibuprofen, as well as with different mixing orders. Turbidimetric studies to find the stoichiometry of the resulting EPO/IB PLC were performed spectrophotometrically (Lambda 25, PerkinElmer, U.S.A.) at a wavelength of 600 nm. Thermal analysis was performed by modulation differential scanning calorimetry (mDSC) on a Discovery^™ DSC instrument (TA Instruments, U.S.A.). Samples sealed in Tzero aluminum pans (TA Instruments, U.S.A.) were scanned in the temperature range from 0 to 250 °С at a speed of 2 °С/min. IR spectra were recorded on a Nicolet iS5 FT-IR spectrometer (Thermo Fisher Scientific, U.S.A.) with an ATR nozzle, in the range from 500 to 4000 cm^-1. Drying of samples of complexes and dispersible tablets was carried out in a FreeZone 1L laboratory freeze dryer (Labconco, U.S.A.) for a 24 hours at a temperature of –49 °C and at a pressure of 0.350 mbar. The drug release was evaluated on a dissolution tester DT 828 (ERWEKA GmbH, Germany) in a volume of 900 ml, at 37 ± 0.5 °C and a blade rotation speed of 50 rpm.

Results and discussion. Studies on the formation of PDC Eudragit^® EPO/ibuprofen (EPO/IB) were carried out at various molar ratios. On samples of PDC and individual components, bands are observed that are characteristic both for EPO – at 2770 and 2820 cm^-1, confirming the presence of non-ionized dimethylamino groups, and at 1725 cm^-1, corresponding to the stretching vibrations of carboxyl groups. A new band is appeared at 1573 cm^-1, which confirm the formation of ionic bonds between carboxylate groups of IB and ionized dimethylamino groups of EPO. The mDSC thermograms of the samples are characterized by a single glass transition temperature (T_g) at 27,3 ± 0,3 °С (for molar ratio 1 : 2) and 44,9 ± 0,4 °С. (for molar ratio 1 : 1), which confirm the formation of polymer-drug complexes. Received PDC Eudragit^® EPO/ibuprofen in a molar ratio of 1 : 2 and 1 : 1 and oral dispersible tablets based on them by lyophilization. The resulting systems are characterized by immediate release of IB with maximum rates at 30 min for a 1 : 1 composition and 60 min for a 1 : 2 composition.

Conclusion. Eudragit^® EPO/ibuprofen polymer drug complex can be used to develop orodispersible tablets providing immediate release of IB.

Introduction. The study of rheological properties (dynamic and plastic viscosity, yield strength, the degree and presence of a thixotropic effect, the nature of the type of flow) are important for the development of soft dosage forms. These properties affect the stability of the dosage form during storage, its technological and consumer characteristics .

Aim. Study of the main rheological parameters of the developed gels and creams on various carrier bases.

Materials and methods. Meloxicam as active ingredient and excipients: sodium alginate, twin-80, propylene glycol, cremophor, glycerin, essential oils of lemon and orange, carbopol 980, polyethylene glycol-400 (PEG-400), viburnum bark, chamomile flowers, chlorhexidine bigluconate 20 %, menthol, sorbitol, corn oil, distilled monoglycerides (MHD), cetyl alcohol, coconut oil, salicylic acid, emulsion wax, preparation OS-20, triethanolamine (TEA), and euxil PE 9010 were used for the preparation of ex[eroimental samples. Three laboratory samples of soft formulations with the mass of 100 g each were prepared. The rheological properties of the samples were tested 24 hours after their preparation using Anton Paar DV-2P viscometer (Anton Paar GmbH, Austria), spindle L4. The structural and mechanical properties of the samples were tested using a device designed at the St. Petersburg State Chemical and Pharmaceutical University under thesupervision of Professor, Doctor of Pharmaceutical Sciences V. A. Vainshtein.

Results and discussion. The greatest mechanical stability was observed for the sample No. 1 (gel based on alginate) and sample No. 3 (cream). The ascending and descending hysteresis loop curves indicates that the test samples have thixotropic properties. Samples No. 1 and 2 have upward and downward flow curves superimposed on each other.This phenomenon is typical for all gels and is their feature. The relaxation of the structure of an elastic-plastic material after the deformation caused by the introduction of a tester stock occurs according to the logarithmic law. At rest, when the tester stockis not introduced into the material, the structure of tested samples is intact and samples has a maximum density (static viscosity). The introduction of the tester stock into the sample results in plastic deformation and forced flow. The tension at the moment of tester stock introduction reflects the yield strength.Further, with the immersed tester devoce, a thixotropic recovery of the destroyed structural bonds occurs. Such a pattern in the dynamics of structure resistance is observed for structured (non-Newtonian) liquids.

Conclusion. The rheological properties of three experimental soft formulations made on different carrier bases were investigated. The importance of rheological studies in the drug development of high e quality soft formulations was shown.

Introduction. Prevention and treatment of periodontal diseases remains one of the urgent problems of modern medicine. According to WHO, the prevalence of dental diseases among adults is 90–95 %, among adolescents – 80–83 %. The health of the body as a whole largely depends on the state of the oral cavity. It is important for the effective treatment of diseases to have a properly selected dosage form, which provides both convenience of use and purposeful use of the action of the pharmacologically active drug contained in it. Medicinal pencils as a dosage form are very limited on the pharmaceutical market, so their development is relevant. As a local anesthetic component, anilocaine is included in the composition of pencils at a concentration of 5 %, antimicrobial action is provided by the introduction of metronidazole in a concentration of 1 % in order to prevent the occurrence of infection.

Aim. Substantiation of the composition and technology of the medicinal pencil for the treatment and prevention of infectious and inflammatory diseases of the oral cavity.

Materials and methods. For the study, we used medicinal pencils with an active pharmaceutical substance – anilocaine (FS 42-2846-97, LLC "Perm Chemical Company", Perm, shelf life of 5 years), metronidazole (FS 42-0257-07, JSC "Medisorb", Perm, shelf life of 3 years); basic components – PEO-400 (FS 42-1242-96, LLC "Neftegazkhimkomplekt", Moscow, shelf life of 3 years), PEO-1500 (FS 42-1885-96, LLC "Neftegazkhimkomplekt", Moscow, shelf life of 3 years), PEO-4000 (FS 42-3337-96, LLC "Neftegazkhimkomplekt", Moscow, shelf life 3 years), second ingredient – purified water (FS.2.2.0020.18), the UVOI-"MF" 1812S6 obtained at the reverse osmosis plant (JSC "NPK Median-Filter", Russia). In the course of the research, technological, structural-mechanical and biopharmaceutical methods were used.

Results and discussion. Based on technological, structural-mechanical and biopharmaceutical studies, the composition of medicinal pencils with anesthetic, anti-inflammatory and antimicrobial effects for the treatment and prevention of infectious and inflammatory diseases of the oral cavity is proposed and justified for the first time. Biopharmaceutical availability of medicinal pencils is determined by the conductometric method.

Conclusion. The conducted complex of studies will expand the range of domestic medicines for the treatment and prevention of infectious and inflammatory diseases of the oral cavity.

Introduction. Usage of organophosphate pesticides (OPPs) in agriculture, including farming of medical herbs, is a necessary measure for producing regular harvest. In order to maintain an adequate degree of herbal medicines security a variety of countries developed normative documents that regulate the limits of proportion of pesticides (including OPPs) in herbal substances. These documents contain the recommended methods of residual pesticides analysis as well.

Text. The article describes the recently conducted information-analytical research of limits of permissible proportion of OPPs in herbal substances and food production and of methods of extraction and analysis of OPPs mentioned in the State Pharmacopoeia of the Russian Federation XIV, international pharmacopeias, WHO information sources and the normative documents on food production. The authors specify physical-chemical characteristic of OPPs and the main mechanism of impact of this class of pesticides onto a human body. The research demonstrates that HPLC-MS and GC-MS are the most perspective analytical methods of detection of OPPs in herbal substances.

Conclusion. In the information-analytical review the authors specify a physical-chemical characteristics of OPPs, describe the mechanism of the toxic impact of this type of pesticides, provide the generalized summary of limits of permissible proportion of OPPs in herbal substances and in food production. The study shows that the rationing of OPPs proportion is harmonized in a majority of issues of modern pharmacopeias. The paper presents modern methods of detection of OPPs in herbal substances and food production. Finally, the authors demonstrate an advantage of the modern approach to rationing of OPPs in herbal substances (specification of presence and proportion of a single pesticide in combination with its toxic metabolites). The key issue is a necessity of developing a sensible and selective methodic of analysis of OPPs in accordance with physical-chemical properties of these types of pesticides in different kinds of herbal substances and phytopreparations.

Introduction. Nowadays, herbal medicines are becoming more and more popular. In this regard, herbal medicinal preparations based on rhizomes and roots of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., syn. Acanthopanax senticosus (Rupr. & Maxim.) Harms, are of particular interest. Its have an adaptogenic, immunomodulatory effects mainly due to the presence of phenyl propane compounds: eleutherosides B, D, E, E1. The current pharmacopeial monographs FS.2.5.0053.15 "Eleutherococcus senticosus rhizomes and roots" and FS.3.4.0009.18 "Eleutherococcus senticosus rhizomes and roots liquid extract" in The State Pharmacopoeia of the Russian Federation XIV Edition, in our opinion, does not allow to fully objectively and uniformly assess the quality of raw materials and preparations.

Aim. The aim is substantiation of new approaches to quality control of raw materials and preparations of Eleutherococcus senticosus, consisting in changing the conditions of sample preparation and analysis of active biological compounds in comparison with pharmacopoeial methods.

Materials and methods. Samples of the medicinal preparation "Eleutherococcus extract liquid" of a domestic manufacturer (5 lots) and experimental preparation "Eleutherococcus syrup". When performing high performance liquid chromatography (HPLC) analysis, a reference sample of syringin was used that met the requirements of pharmacopeial monograph VFS 42-2088-92. Methods of UV-spectroscopy and HPLC were used to determine the quantity of biologically active substances.

Results and discussion. As a result of the research, other methodological and methodological approaches have been developed to determine the content of the total of phenylpropanoids in terms of eleutheroside B (syringin) by direct UV-spectrophotometry using a standard sample of syringin or the value of its specific absorbance. New conditions for HPLC analysis of eleutheroside B (syringin) in preparations of Eleutherococcus senticosus have been selected.

Conclusion. As a result of the phytochemical study, a spectrophotometric method was developed for the determination of the total of phenylpropanoids in terms of syringin and an HPLC method for the determination of eleutheroside B (syringin) using an external standard after preliminary purification of the total extracts by filtration through a layer of aluminum oxide.

Introduction. Recently, IR spectroscopy has been increasingly used to identify various groups of biologically active substances (BAS) in plant objects. It is known that plants are capable of accumulating various BAS. Currently, there is no reliable, complete and accessible database of IR spectra of medicinal plant raw materials (MPR), which has a multicomponent composition, which is necessary for solving specific practical problems. It is of interest to use express methods of non-destructive testing for the purpose of identifying medicinal plant raw materials, as well as differential diagnostics of closely related species and various varieties of medicinal plants, which allow the analysis of raw materials in the shortest possible time, while maintaining the possibility of further vegetation. These types of difficult to distinguish raw materials include 9–14 (according to various sources) closely related plant species of the genus Valeriana, included, according to the accepted classification of V. I. Grubov with additions and changes by V. N. Voroshilov in the collection cycle (V. officinalis L.) of the Officinales Grub. series, and are characterized by an extremely similar composition of the metabolome.

Aim. The purpose of this study was to study the possibility of using IR spectroscopy for the identification of MPR of Valeriana wolgensis Kazak. and Valeriana dudia L.

Materials and methods. The objects of the study were rhizomes with roots, grass of Valeriana wolgensis Kazak. and Valeriana dudia L. Samples were col-lected in the Voronezh region in 2019 on the banks of the Ikorets river in the village of Sredny Ikorets, Liskinsky district and in the vicinity of the village of Belogorye, Podgorensky district. IR spectra were obtained without preliminary sample preparation on a IR Fourier spectrometer VERTEX 70 (Bruker, Germany) by the disturbed total internal reflection method and subsequent pro-cessing with the OMNIC or GRAMS 4/32 program.

Results and discussion. In all spectra of the studied samples, absorption bands reflecting the general chemical composition were found. Similar absorption bands were observed, differing only in intensity. The spectra of similar groups of raw materials (herbs and rhizomes with roots) of the studied species of Valeriana were especially close to each other. In the IR spectra of the powders of the medicinal product under study, one can distinguish absorption bands characteristic of the hydroxyl groups of the cyclopentanepyrane skeleton of valepotriates: 3296–3280 cm^-1. The complex absorption band in the region of 2958–2844 cm^-1 is due to stretching vibrations of numerous methyl and methylene groups. Bending vibrations of the same groups give characteristic peaks at 1751–1407 cm^-1 and about 700 cm^-1 (790–720 cm^-1 – pendulum vibrations of methylene groups). At the same time, among the main BAS of this medicinal product, the dominant compounds are those in which the methylene groups are closed in unstressed rings, which is manifested in bands in the range of 1420–1400 cm^-1. The absorption bands in the range of 3296–3280 cm^-1 in the IR spectra of the medicinal product of the studied species are due to stretching vibrations of the hydroxyl group in intermolecular hydrogen bonds. Based on the data obtained, the thermodynamic characteristics of the identified bonds, such as energy (EH) and length (R), were calculated. Valepotriates containing a cyclopentanepyran skeleton with five hydroxyl groups – polyhydrooxycyclo-pentanepyrane, in the studied medicinal plant, according to IR data, polyassociates are formed with characteristic absorption frequencies at 3400–3200 cm^-1. The specific frequencies identified in the spectrum can be considered characteristic for a certain type of raw material of Valeriana and can be used as markers in determining the authenticity and species by the IRS method.

Conclusion. The studies have shown that the IR Fourier spectroscopy of the disturbed total internal reflection can be used to obtain individual IR spectra of MPR of various morphological groups. The data obtained, in general, indicate the similarity of the chemical composition of two closely related species of valerian harvested in the Voronezh region, which, in addition to other studies of the metabolome composition, justifies the possibility of their use along with the official raw material of Valeriana officinalis L. The formation of hydrogen bonds and their character between BAS molecules in the studied medicinal product was established by IR spectroscopy. The results obtained indicate that the method used is promising for the rapid assessment of the medicinal product authenticity.

Introduction. The research results obtained through the analysis of different varieties of Rhodiola rosea rhizomes and roots using high-performance thin layer chromatography (HPTLC), grown in the Saint-Petersburg State Chemical-Pharmaceutical University (SPCPU) medicinal plants nursery garden, are represented.

Aim. To carry out a comparative analysis of Rhodiola rosea rhizomes and roots samples, grown in the SPCPU medicinal plants nursery using HPTLC.

Materials and methods. HPTLC analysis was performed on a CAMAG device (Switzerland), using MERCK HPTLC silica gel 60 F 254, 20 × 10 cm plates. Extracts were obtained from raw materials using an ultrasonic bath "Sapphire-4.0 TTC" (Russia). The Rhodiola rosea rhizomes and roots were harvested in the SPCPU medicinal plants nursery garden (Leningrad Region, Vsevolozhsk district, Priozerskoe Highway, 38 km) in August 2019.

Results and discussion. In the course of the research, extracts from Rhodiola rosea rhizomes and roots were obtained using 70 % ethyl alcohol and methyl alcohol as extractants. The extracts were investigated by HPTLC in ethyl acetate – methanol – water – formic acid (77 : 13 : 10 : 2) solvent system. After scanning densitometric analysis at 254 nm, the much better separation of methanol extracts in this solvent system was found than ethanol extracts. The densitograms of individual tracks were compared with each other in order to identify samples of Rhodiola rosea rhizomes and roots with a higher biologically active compounds content. As a result of the comparison of 18 samples tracks of the Rhodiola rosea rhizomes and roots (the extractant was ethyl alcohol 70 %), samples № 6 and 17 have been proposed as promising for further research and cultivation.

Conclusion. As a result of the analysis of alcohol extracts from Rhodiola rosea rhizomes and roots by HPTLC, the samples 6 (Tomsk, Russia) and 17 (Valla Di Aposta/Hirvos varieties, country of origin – Italy/Finland) were found to have a higher content of biologically active compounds.

Introduction. The search for new tools for the treatment and prevention of obesity – a socially significant disease characterized by high prevalence and the presence of a number of complications – is an urgent area of research. Literature data indicate the presence of pharmacological activity in different groups of BAC of plant origin – flavonoids, phenolic acids, phytosterols, etc. in relation to obesity and its associated diseases. In view of the significant accumulation of target groups of compounds, as well as the availability of a large and renewable raw material base, celery was chosen for research as a potential raw source of BAC contributing to the regulation of metabolic disorders.

Aim. To investigate the component composition of lipophilic fractions of botanical forms of celery by GC/MS and to predict the pharmacological activity of identified compounds within the target group of pathologies using the web resource PASS Оnline.

Materials and methods. Lipophilic fractions were prepared by chloroform extraction of dry crushed raw material of celery root, stalks and leaves in a Soxhlet apparatus. Obtained extracts were analyzed on gas chromatography-mass spectrometer "Clarus 600T" (PerkinElmer, USA) on the basis of the Collaborative Centre "Analytical Center" equipment. Interpretation of the mass spectra of the peaks on the chromatograms was carried out using the NIST-14 library, for further prediction of biological activity of the identified compounds we used web-resource PASS online.

Results and discussion. The composition of lipophilic fractions of celery botanical forms is represented by terpenes, benzofurans, coumarins, fatty acids and their derivatives, phytosterols. A total of 50 compounds were found in extracts from celery root, of which 68 % were identified, stalks – 36 and 61 %; leaves – 22 and 64 %, respectively. Prediction of the pharmacological activity of individual compounds of celery showed the possibility of their use for the regulation of lipid and carbohydrate metabolism, cardiovascular disorders and liver diseases, which confirms the prospects of this study.

Conclusion. The results have shown that celery roots and stalks are a source of terpenes, coumarins and benzofuran derivatives, in addition, the above-ground part of the plant shows high accumulation of phytosterols, which may have metabolic regulation activity and be used in the complex therapy and prevention of obesity.

Introduction. This work is devoted to the intestinal permeability study of 7-(2-chlorophenyl)-4-(4-methyl-1,3-thiazol-5-yl)-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-dione – innovative biologically active substance with TRPA₁ antagonist activity. The phenyltetrahydroquinolinedione derivative is a promising analgesic and anti-inflammatory drug. To develop a dosage form of this new substance, it is necessary to study the mechanism and degree of its absorption.

Aim. The aim of this work was to investigate the intestinal permeability of the phenyltetrahydroquinolinedione derivative using Caco-2 cell model and to compare experimental results with the in silico obtained values of the octanol/water partition coefficients.

Materials and methods. The study of permeability was carried out from the apical membrane to the basolateral (A-B) and in the opposite direction (B-A). Ranitidine (low permeability), propranolol (high permeability) and rhodamine 123 (P-glycoprotein substrate) were used as control compounds. The concentration of the test compound was determined by UHPLC-MS/MS system consisting of a liquid chromatograph and a tandem mass spectrometer with a triple quadrupole and an electrospray ion source. The logP was calculated using the following resources: ChemDraw Professional 16.0, Molinspiration, ALOGPS 2.1.

Results and discussion. The values of the apparent permeability (P_app) and efflux ratios of the test and control compounds were obtained. According to the results of the study, the following conclusions were made: the test compound has high permeability both in the forward direction from the apical to the basolateral cell membrane, and in the opposite direction (P_app > 10 × 10^-6 cm/s). P-glycoprotein-mediated efflux activity was not observed (the efflux ratio was less than 2 units). The permeability did not depend on the test compound input concentration. The obtained experimental P_app values were correlated with the in silico obtained values of partition coefficients. The best correlation was obtained for milogP (Molinspiration) and ClogP (ChemDraw).

Conclusion. Thus, the in vitro and in silico obtained data indicate that passive diffusion is the main mechanism of absorption of the test compound in the gastrointestinal tract.

Introduction. The increase in the incidence of whooping cough in children and adults of different age groups justifies the need for their revaccination and the development of new, acceptable for these purposes. This work is devoted to substantiating the design of a clinical trial and describing the results of a comparative study of the safety and tolerability of the drug "GamLPV" with two-fold intranasal administration to healthy adult volunteers using two methods. The choice of the scheme and method of administration of the drug is justified. The serological structure of the population of adults aged 18–40 years living in Moscow and the Moscow region is characterized.

Aim. Determination of the safety and tolerability of the drug with a double intranasal administration of the vaccine by drip method and spraying through an actuator.

Materials and methods. A randomized placebo-controlled trial included 50 healthy male and female volunteers aged 18 to 40 years who met the inclusion criteria. The volunteers were divided into 2 groups of 25 people: a drip method of administration and spraying through an "actuator". By both methods, the drug was administered twice with an interval of 60 days.

Results and discussion. Serological analysis of the population of healthy volunteers at the prescreening stage justified the inclusion in the study of volunteers containing anti-pertussis antibodies in the blood (IgG ≤40 Ed/ml). A comparison of the results of preclinical studies on an experimental model of non-human monkeys and the first phase of a clinical study of GamLPV allowed us to propose two methods of double administration of the drug as a promising vaccination scheme for volunteers. A comparative randomized study shows the safety of using the proposed scheme for vaccination of adult volunteers.

Conclusions. Both proposed methods of double administration can be used to plan a multicenter study to research the immunogenicity and protective activity of GamLPV.

Introduction. In modern pharmacology, more and more widely used molecular complexes (MC) based on donor-acceptor or, on weaker, intermolecular interactions, to stabilize dosage forms in the composition of pharmaceutical substances or their targeted delivery. This trend is actively developing, because the molecules forming MK, which has a certain composition and spatial structure, are preserved and can be released unchanged. The use of MC in tandem with "classical" metal-containing coordination compounds, which enhance or modify the action of the active component, allows the development of new, more effective drugs with optimized bioavailability and activity.

Aim. Evaluation of the wound-healing effect of new substances based on aqueous systems containing coordination compounds of copper(II) or zinc with MC adenosine-copolymer of N-vinylpyrrolidone, in comparison with the drug Depantol® on a model of thermal burn in mice.

Materials and methods. Mononuclear alainate complexes Cu(Ala)₂ · H2O and Zn(Ala)₂ (Ala – alainate-anion), copolymer of N-vinylpyrrolidone with crotonic acid (PVP-CA) have been synthesized. The composition of the obtained compounds was confirmed by the data of elemental analysis on a CHN (S) analyzer LECO CHNS (O) 932 (Elemental Microanalysis Ltd, Great Britain). IR spectra of the samples were recorded on a IRAffinity-1 (Shimadzu, Japan) instrument (by tabletting a sample with KBr) and a IRTracer-100 (Shimadzu, Japan) instrument equipped with a Specac Quest ATR attachment (Shimadzu Corporation, Japan). Potentiometric titration of the functional groups of the VP copolymer was performed using a PP-20 pH meter (Sartorius AG, Germany). The solutions of the preparations were prepared by dissolving PVP-KK in polyethylene glycol (PEG-400), followed by the addition of an aqueous dispersion of adenosine (Ad) and the corresponding complex of copper(II) or zinc into the preparation. After modeling a thermal burn of the third degree, the overall mortality in the groups and the dynamics of healing of the injured area were assessed. During the experiment, histological studies of areas of damaged tissue after staining of preparations with hematoxylin and eosin were carried out and a generalized scoring assessment of the characteristics of the burn process was carried out, including an assessment of the width and depth of the formed scar tissue, the severity of inflammatory infiltration and the presence of hemosiderosis in the tissues.

Results and discussion. The formation of the MC of the copolymer of N-vinylpyrrolidone with crotonic acid with adenosine made it possible to prepare solutions of preparations containing up to 5 % (wght.) Of the latter. In the obtained samples, the molar ratio of PVP-CA : Ad : M(Ala)₂ was 100 : 10 : 1 (M = Cu^II, Zn), the pH level of the obtained preparations was 7.0–7.1. The resulting funds were applied to the damaged area of the skin in a volume of 0.1 ml/day, each individual, daily for 4 weeks. Introductory substances based on MC PVP-CA : Ad : M(Ala)₂ showed a moderate wound healing effect in comparison with the drug Depantol®, based on a water-fat emulsion. Substances that do not contain a metal complex and contain Cu(Ala)₂ showed better efficiency in the dynamics of healing a burn injury in comparison with other studied substances, which was combined with a low mortality rate of experimental animals in these groups (3 cases and 2 cases out of 9 individuals, respectively). The reference drug – Depantol®, in turn, showed the best result, probably due to the content in its composition, in addition to dexpanthenol, which is characterized by a wound-healing effect, chlorhexidine antiseptic, and a fatty base, which reduces the dehydration of the injured area.

Conclusion. Experimental substances based on aqueous solutions of adenosine-polymer MK showed a moderate wound healing effect comparable to the reference drug, which, however, is of sufficient interest for further study of such compositions, or their modified versions with the addition of antimicrobial components on thermal burn models, in order to creation of new, more effective drugs for the healing of wound surfaces.

Introduction. Coronavirus disease (COVID-19) is an acute infectious disease caused by SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2). Favipiravir is a synthetic prodrug with antiviral activity used for the treatment of COVID-19. There are oral and parenteral dosage forms of favipiravir. Compared with oral administration, parenteral administration has some advantages. Developing a method for the determination of favipiravir in human blood plasma is necessary for performing the analytical part of clinical studies of favipiravir for parenteral administration as an infusion, studying pharmacokinetics, and choosing the optimal dosage of the drug.

Aim. The aim of this study is to develop and validate a method for quantitative determination of favipiravir in human plasma by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) for pharmacokinetic studies.

Materials and methods. Determination of favipiravir in human plasma by HPLC-UV. The UV detection was set at 323 ± 2 nm. The samples were processed by methanol protein precipitation. Internal standard: raltegravir. Mobile phase: 0.1 % formic acid in water with 0.08 % aqueous ammonia (eluent A), 0.1 % formic acid in acetonitrile with 0.08 % aqueous ammonia (eluent B). Column: Phenomenex Kinetex^®, C18, 150 × 4.6 mm, 5 μm. Analytical range: 0.25–200.00 μg/mL.

Results and discussion. This method was validated by selectivity, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability.

Conclusion. We developed and validated the method of quantitative determination of favipiravir in human plasma by HPLC-UV. The analytical range was 0.25–200.00 μg/mL in human plasma. The method could be applied in pharmacokinetics studies of favipiravir.

Introduction. The article considers the issues of forming a reserve of antibacterial agents designed to eliminate medical and sanitary consequences of emergencies from the perspective of national drug security.

Aim. To determine the degree of import substitution of antibacterial agents included in the regional drug reserve.

Materials and methods. We carried out a content analysis of data from regulatory documents and research papers related to formation of drug reserves, a logical and structural analysis of the range of antibacterial agents included in the reserve of the Tomsk region, and an analysis of data from the National Drug Register. In the study, we used the Anatomical Therapeutic Chemical (ATC) Classification System of drugs.

Results and discussion. It was established that for 19 international nonproprietary names (INN) of antibacterial agents belonging to the group of antibacterials for systemic use (ATC code J01) and forming the reserve of the Tomsk region, 294 brand names (BN) were registered on the pharmaceutical market of the Russian Federation in 2021. The share of registered domestic BN was 49.3 %, and the degree of import dependence of domestic drug manufacturing on foreign-made active pharmaceutical ingredients (APIs) was 81.4 %. It was found that 6 Russian enterprises manufacture APIs that supply production of 10 antibacterial agents included in the drug reserve. A classification of medicines by strategic availability for replenishing the drug reserve was developed. A map on strategic availability of domestically manufactured antibacterial agents included in the reserve was drawn up.

Conclusion. We demonstrated high dependence of antibacterial reserve formation on import of this group of medicines and APIs to the Russian Federation. The classification of medicines which takes into account the possibility of replenishing the drug reserve in emergency conditions and if import of medicines stops can be recommended for use by the center for disaster medicine to optimize the nomenclature of drug reserves at various levels from the perspective of national drug security promotion.