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Introduction. Biorelevant dissolution media reconstitute the composition of the contents of the gastrointestinal tract. They are used as dissolution media in the evaluation of dissolution profiles of different dosage forms. Simulated biological fluids allow prediction of in vivo test results. The development of the composition of simulated salivary fluid allows the evaluation of drug properties under physiologically relevant conditions.Aim. Evaluation of the release of the drug product "glycine, sublingual tablets, 100 mg", domestically produced in Simulated Saliva 5 pH 6.8.Materials and methods. The preparations used for analysis were: «Glycine, sublingual tablets, 100 mg», domestically produced with valid expiration date. Comparative dissolution kinetics test was carried out on the dissolution test apparatus DT 6 (ERWEKA GmbH, Germany). Chromatographic separation and detection were performed on a Waters W1525 Binary HPLC Pump high-performance liquid chromatograph (Waters Corporation, USA) equipped with column and sample thermostat, degasser, autosampler and Waters 2487 Dual Absorbance Detector (Waters Corporation, USA). Detection was performed at a wavelength of 254 ± 2 nm after derivatization of the glycine molecule with 4-toluenesulfonyl chloride. A Grace Platinum C18-EPS 5 μm 4.6 × 250 mm Grace Platinum C18-EPS 5 μm 4.6 × 250 mm column (Grace, USA) and a Grace Platinum C18-EPS 5 μm 4.6 × 250 mm pre-column (Grace, USA) were used. The following software was used for the study: validated Microsoft Excel spreadsheet for calculating glycine release values.Results and discussion. The technique for quantitative determination of glycine was developed and validated under CDKT in purified water medium and Simulated Saliva 5 pH 6.8. The validated analytical range of the methodology was 10–110 % of the nominal concentration of the dosage form in 300 mL volume of medium. The developed analytical technique was validated in the biopredictive in vitro test of glycine preparations. During the study in Simulated Saliva medium for drug formulations, more discriminative data were obtained, which were expressed as: different dissolution rate, curvature of the slope of the dissolution profile and time to reach the plateau in contrast to the dissolution medium purified water.Conclusion. The quantification technique was developed and validated for biopredictive tests of tablets "Glycine, sublingual tablets, 100 mg". The analytical range of the technique was 10–110 % of the nominal concentration of the dosage form in 300 mL volume of medium. The results of the test in artificial saliva medium were more discriminatory.

Introduction. Representatives of the Ericaceae family are quite common in Russia and are promising for the creation of new medicines of plant origin. At the same time, only 4 of them are official. The study of biologically active substances and pharmacological activity of Andromeda polifolia L., Chamaеdaphne calyculata (L.) Moench, Ledum palustre L., Empetrum nigrum L. with rich resource reserves is promising.Aim. Comparative study of the composition of total flavonoid fractions from A. polifolia, C. calyculata, L. palustre, E. nigrum and study of their effect on the NO-stimulating activity of peritoneal macrophagesMaterials and methods. The crushed aboveground part (leafy shoots) was previously depigmented with chloroform, treated with 70 % aqueous acetone, then acetone was removed. Flavonoids were extracted with ethyl acetate from the aqueous phase. The identification of flavonoids was carried out by HPLC (UltiMate 3000 chromatograph) according to the coincidence of retention times and spectral characteristics, the calculation of the content was carried out by simple normalization. The effect of the samples on nitric oxide production was studied on macrophages of C57BL/6 mice. Endotoxin control in the samples was carried out using a LAL test and cell incubation in the presence of polymyxin B.Results and discussion. The composition of flavonoid fractions from A. polifolia, C. calyculata, L. palustre and E. nigrum has been studied. 8 phenolic compounds were found in C. calyculata shoots, including isoquercitrin, herbacetin, naringenin and naringin – for the first time for this species. 5 compounds were detected in A. polifolia shoots, including isoquercitrin and herbacetin, for the first time for this species. 5 and 4 compounds were identified in L. palustre and E. nigrum shoots, respectively, while quercetin glycosides are predominant in all samples: isoquercitrin, hyperoside and rutin. The fraction of C. calyculata flavonoids at doses of 1, 5, 10 mcg/ml inhibits the production of nitric oxide by macrophages by 30 %, and E. nigrum flavonoids at doses of 100 and 200 mcg/ml, on the contrary, enhance the production of nitrites by macrophages by 33 and 37 %, respectively.Conclusion. A comparative study of the composition of total flavonoid fractions from A. polifolia, C. calyculata, L. palustre, and E. nigrum, which are capable of activating both M1 and M2 polarization of peritoneal macrophages in mice, has been conducted, which requires further in-depth study. The flavonoids C. calyculata and E. nigrum are promising for further study.

Introduction. The development of defect-free film coating modes is an urgent task when transferring film-coated tablets technology. Technology transfer is an integral stage of the life cycle of any drug approved for industrial production. During the development of the technological process, deviations may occur, to eliminate which it is necessary to introduce auxiliary operations or change the chain of technological equipment.Aim. Optimize the process of applying a film coating to tablets of the core of the vitamin and mineral complex.Materials and methods. The objects of the study were biconvex core tablets in the form of a boat of a vitamin and mineral complex consisting of vitamins C + E + B1 and minerals. To ensure the required technological properties, auxiliary substances were used: microcrystalline cellulose, sodium croscarmellose, potato starch, calcium stearate, colloidal silicon dioxide. Ready-made film-forming mixtures (Colorcon®) in beige Opadry® II 85F 270000 were used as film-forming compositions. The film coating was applied in the craters with a perforated drum BG-80 (Pro-face, China) and BGK-150 (Zhejiang Canaan Technology Limited, China).Results and discussion. The process of applying a film coating to the core tablets of a vitamin and mineral complex has been studied. The analysis of the current technological chain showed a number of disadvantages – a large amount of manual labor, the need for matting the drum, the duration of the process, low loading, braking of the production cycle due to lagging at the stage of applying the film shell. To solve the discovered problems, a project was developed to scale the technology at the stage of applying a film shell to tablets-the cores of a vitamin and mineral complex. During the implementation of the process, new equipment was purchased and installed for production. The development of the technological process made it possible to multiply the one-time loading into the boiler (by 2–3 times), automate the process due to the automatic operation function according to the parameters set before the start of the technological process, and exclude the matting of the drum from preparatory work. The quality of film-coated tablets has improved, and the risk of defects has significantly decreased.Conclusion. During the study, it was proved that transferring the film coating process to another piece of equipment can improve the quality of the resulting film-coated tablets and optimize the technological process. A multiple increase in the loading size is not carried out at the same time by changing the number of nozzles and the inner section of the hose for applying the film coating material.

Introduction. The development and registration of antiviral drugs is an urgent task. Flavonoids, in particular, luteolin-7-glycoside (cinaroside, luteolin-7-O-glycoside) demonstrate high broad-spectrum antiviral activity in vitro, and the industrial regulations for the production of luteolin-7-glycoside from the leaves of holly willow have already been developed at the VILAR. One of the problems with the introduction of flavonoids into medical practice is their low bioavailability and intensive biotransformation. Existing publications provide contradictory data on the pharmacokinetics of luteolin-7-glycoside, and therefore our own research was conducted.Aim. To develop a methodology for the quantitative analysis of luteolin-7-glycoside and its metabolites in blood plasma and to test it on laboratory animals.Materials and methods. Animal experiments were carried out in accordance with the requirements of the "Guidelines for conducting preclinical studies of medicines". To develop a method of analysis and further clarify the time intervals of blood sampling, time points were analyzed: 30, 60 minutes, 2, 4, 8, 24 hours after administration of the test substance. Tubes with citrate blood of laboratory animals were centrifuged at 2000 rpm for 10 minutes. The plasma was placed in an Eppendorf-type test tube, frozen and stored at –20 °C until chromatographic analysis was performed. Blood plasma sample preparation was carried out by precipitation with methyl alcohol, the supernatant was chromatographically separated on a column Luna® 5 µm C18 column 100 Å 250 × 4.6 mm in a gradient mode in a water-acetonitrile system and a modifier – 0.2 % formic acid. The metabolites were identified by high-performance liquid chromatography with mass spectrometric detection. To do this, the spectral characteristics of the peaks that appeared on the chromatograms of blood plasma samples after oral administration of luteolin-7-glycoside were interpreted. The concentration of the analyzed substances was assessed by the internal standard method, which was rutin. To determine the concentration of luteolin, a standardized luteolin substance was used as a standard sample, the concentration of the remaining metabolites was estimated in terms of luteolin.Results and discussion. It was found that after oral administration of luteolin-7-glycoside in starch paste to laboratory animals, native luteolin-7-glycoside was not detected in blood plasma. The main metabolites were luteolin-diglucuronide and luteolin-glucuronide, their maximum plasma concentrations are about three times higher than luteolin and methyllyuteolin-diglucuronide. The results are compared with data from other studies.Conclusion. The absence of native luteolin-7-glycoside in blood plasma after oral administration makes it necessary to seriously reconsider the relevance of the conclusions obtained during studies of its activity in vitro. However, in the presence of antiviral activity in vivo, there is an urgent need for further research to establish the real mechanisms of action of this medicinal substance.

Introduction. In the pharmaceutical technology field there is great interest in polymers with mucoadhesive properties, as they increase the drug retention time on the mucosal surface and increase the bioavailability of the drug. There are various mucoadhesive drug delivery systems: tablets, films, gels, suspensions of micro- and nanoparticles, etc. The ability to adhesion depends on the excipients, especially on their chemical structure. Molecular weight, surface charge, flexibility of the polymer chain and the presence of various functional groups play an important role. Polymers under the trade name Eudragit®, produced by the German concern Evonik Nutrition & Care GmbH, have been used in the pharmaceutical field for several decades to produce controlled-release oral dosage forms. Eudragit® EPO (EPO) is a ternary copolymer based on methacrylic acid derivatives and has mucoadhesive properties due to the presence of dimethylamino groups in its structure. The proposed chemical modification of Eudragit® EPO with a phenylboronic acid derivative, due to the presence of hydroxyl groups in their structure, leads to additional interaction with mucin oligosaccharides, providing enhanced mucoadhesive properties of this polymer.Aim. Synthesis and study of a chemically modified Eudragit® EPO using 4-bromophenylboronic acid in order to increase the mucoadhesive properties of the copolymer for use in transmucosal drug delivery systems.Materials and methods. The synthesis of chemically modified Eudragit® EPO (BEPO) was carried out for 24 hours at 50 °C, followed by purification by dialysis using a dialysis membrane (MMO = 12–14 kDa; Medicell International Ltd, UK) for 7 days and freeze drying at –50 °C and 0.05 mbar using Heto Power Dry LL 3000 (Thermo Electron Corporation, USA) for 5 days. Confirmation of the formation of ВЕРО was carried out by ATR-FTIR spectroscopy on a Nicolet iS5 spectrometer (Thеrmо Fisher Sciеntific, USA) and 1H-NMR spectroscopy on a DPX 400 MHz device (Bruker, Germany). Thermogravimetric analysis (TGA) and modulated differential scanning calorimetry (mDSC) were performed using Discovery TGA™ and Discovery DSC™ (TA Instruments, USA), respectively. The study of mucoadhesive properties was performed by the ability to retain the copolymer on the isolated sheep nasal mucosa at 37.0 ± 0.5 °C for 30 minutes.Results and discussion. BEPO was prepared with a substitution degree of dimethylamino groups with phenylboronic acid of 25 % (BEPO25) and 50 % (BEPO50). The yields of BEPO25 and BEPO50 were 40.70 and 30.79 %. The new characteristic band appears at 1605 cm–1 in the IR spectrum of BEPO, which indicates the attachment of phenylboronic acid to EPO. In the 1H-NMR spectrum of BEPO, the formation of additional peaks in the range of 7.8 and 7.5 ppm is observed, which are absent in the EPO spectrum, which indicates the presence of phenylboronic acid. According to TGA results the samples of boronated EPO have the thermal stability similar to the original EPO. The results of DSC analysis show that the glass transition temperature (Tg) of BEPO samples is somehow higher than the original EPO, which is probably associated with a decrease in the amount of free dimethylamino groups in the terpolymer structure. BEPO50 is retained on the surface of isolated sheep nasal mucosa for 30 minutes, while EPO is washed off with artificial nasal fluid in 5 minutes.Conclusion. The development and study of BEPO is a promising direction for further use in transmucosal drug delivery systems.

Introduction. In the modern world, there are many pharmaceutical substances that have various structure. During the development of finished dosage forms (FDPs) it is necessary to take into account many factors, such as physicochemical and technological properties of substances and excipients, manufacturing technology and others. This work is focused on the application of these approaches in practice in relation to a substance with anisodiametric crystal shape. Rebamipide was chosen as an example of such substance with poor technological characteristics for investigation and manufacturing technology selection.Aim. Research of approaches to examine a substance with anisodiametric crystal shape (Rebamipide in this case) to determine its physicochemical and technological properties in purpose of theoretical substantiation of the best method of manufacturing mass for tabletting.Materials and methods. In this study were used such materials as Rebamipide substance (α-[(4-chlorobenzoyl)amino]-1,2-dihydro-2-oxo-4-quinolinepropanoic acid) (experimental sample). Also were used such equipment as flowability tester ERWEKA GT (Erweka GmbH, Germany), powder density tester ERWEKA SVM 122 (ERWEKA GmbH, Germany), vibrating sieve CISA RP 200N (CISA Cedaceria Industrial S.L., Spain), powder diffractometer D8 ADVANCE (Bruker Corporation, USA), calorimeter DSC 204 F1 (NETZSCH, Germany), Hitachi TM-100 electron microscope (Hitachi, Japan).Results and discussion. The properties of Rebamipide substance were evaluated, such as polymorphism, melting point, microscopy and evaluation of technological characteristics. Application of the SeDeM method allowed to determine the critical parameters of the substance that need to be corrected.Conclusion. It was found out experimentally that Rebamipide substance has polymorphism, high melting point, needle-shaped crystals, poor bulkiness and compactability, which was confirmed by the use of SeDeM method.

Introduction. The presence of the active metabolite (3-hydroxyphenazepam, 3-OH-PHEN), the wide interindividual variability of the therapeutic effect of phenazepam (PHEN), as well as its active moiety in the blood, determine the relevance of therapeutic drug monitoring (TDM). To do this, the researcher must have an express analytical technique with a wide analytical range, a low limit of quantification (LLOQ), and with robustness with different sample preparation methods.Aim. Development and validation of quantitative methods for PHEN and 3-OH-PHEN in human blood plasma with different sample preparation methods.Materials and methods. The determination of PHEN and 3-OH-PHEN has been performed by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Solid-phase extraction (SPE) and liquid extraction with support (SLE) otherwise called liquid-liquid extraction in the solid phase were used for sample preparation. Metoprolol was utilized as an internal standard (IS). Gradient elution profile between mobile phase A (0.2 % aqueous formic acid) and B (100 % acetonitrile) has been used. Column: Hypersil GOLD® C18, 50 × 2.1 mm, 3.5 μm.Results and discussion. Two methods have been developed for the quantitative determination of PHEN and 3-OH-PHEN in human blood plasma using different sample preparation methods: SPE and SLE. The conditions of chromatographic separation and mass spectrometric detection of the analytes are selected. The following validation characteristics were determined for both methods: selectivity, calibration curve, accuracy, precision, degree of extraction, LLOQ, carry-over effect, matrix factor, stability of standard solutions and analyte in the matrix.Conclusion. The validation results of the developed methods meet the established criteria, which allows them to be used for the quantitative determination of PHEN and 3-OH-PHEN in human blood plasma. The wide analytical range for both methods 1–1000.00 ng/ml allows the use them for pharmacokinetics and bioequivalence studies, as well as in toxicology.

Introduction. The study of the systemic exposure of a new original drug is an essential part of its preclinical study. 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide is a new selective carbonic anhydrase II inhibitor for the treatment of open-angle glaucoma. Methods for the quantitative determination of this compound and its N-hydroxy- and N-acetyl metabolites in the plasma of laboratory animals have not been previously developed.Aim. Development and validation of a method of quantitative determination of 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide and its metabolites N-hydroxy-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide (M1) and N-acetyl-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide (M2) in rat and rabbit blood plasma by HPLC-MS/MS.Materials and methods. Protein precipitation by methanol was applied for sample preparation. 5-[2-(morpholine-4-carbonyl)-1,3-oxazole-5-yl]-thiophene-2-sulfonamide was used as an internal standard. A 5 % aqueous solution of ascorbic acid was added to the plasma samples at volume ratio 1 : 2 to prevent decomposition of N-hydroxy-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide. The combination of sodium fluoride and potassium oxalate was selected as an anticoagulant. Chromatographic separation was performed on Zorbax Eclipse Plus C18 column (150 × 3.0 mm, 3.5 µm) with Zorbax Eclipse Plus C18 pre-column (12.5 × 2.1 mm, 5.0 µm) using a mobile phase based on a 0.1 % aqueous solution of formic acid and methanol. Mass spectrometric detection was carried out in the MRM mode using electrospray ionization in negative polarity. The method was tested during a pharmacokinetic study of a 1 % ocular suspension of 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide on 6 Wistar rats. Blood samples were collected before administration, as well as 30 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, 144 h, 216 h after administration. The non-compartment approach was used for calculation pharmacokinetic parameters.Results and discussion. The developed method has been validated in parameters of selectivity, calibration curve, accuracy and precision, matrix effect, dilution integrity, carry over, reinjection reproducibility, stability. The analytical range of determination of 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide in plasma was 10–4000 ng/ml, M1 – 1.0–400.0 ng/ml, M2 – 0.1–40.0 ng/ml. The selected combination of anticoagulant and stabilizer solution allows storage of plasma samples in freezing chamber for 28 days.Conclusion. The developed method has been fully validated and confirmed its suitability for quantitative determination of 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide and its metabolites in the blood plasma of laboratory animals. The method has been successfully used for pharmacokinetic study of 1 % ocular suspension of the drug.

Introduction. The use of doxorubicin in clinical practice has shown cumulative and dose-dependent toxic effects on cardiomyocytes, leading to an increase of mortality risk among patients with cancer and as a resulting to restrictions in the indications for its use.Text. A dangerous adverse reaction of doxorubicin is cardiomyopathy, leading to congestive heart failure. Cardiotoxicity is based on at least several pathophysiological mechanisms (described in more detail in the first part of the review), leading to damage to cardiomyocytes as a result of oxidative stress with the formation of free radicals, dysfunction of mitochondria, autophagy, release of nitric oxide and inflammatory mediators, as well as changes in gene expression and proteins leading to apoptosis. The current (second) part of the review provides detailed information on the actual understanding of the pathophysiological mechanisms underlying the described cardiotoxicity, the effect of doxorubicin on other heart cells. The use of cardioprotective strategies will reduce the severity and likelihood of developing cardiotoxicity. This article describes strategies based on reducing the maximum cumulative dose, changing the speed of doxorubicin administration, using pegylated liposomal formulations and cardioprotective agents, as well as exercise.Conclusion. Despite the huge number of scientific papers devoted to various aspects of cardiotoxicity of doxorubicin, its prevention and treatment, this issue requires more careful study and development of more advanced methods of early diagnosis, prevention and more effective therapy the complication.

Introduction. The review considered the basic concepts of drug release and kinetic modeling of this process from dosage forms (DF) according to the dissolution profile using a vertical Franz diffusion cell.Text. Drug release from dosage forms (ointments, gels, transdermal patches and polymer films) is usually described as the processes of drug dissolution in the biological system. Formally, this process, in accordance with pharmacopoeial methods, is assessed using various solubility tests. The theoretical aspects of drug release are based on the theory of mass transfer of substances from a polymer matrix into a system that simulates a biological environment. Drug release can be carried out via the passive diffusion mechanism according to Fick and "non-Fick" diffusion, drug desorption from the inner side of the membrane, as well as other mechanisms. Drug release is determined both lipophilicity and the membrane nature, both various physicochemical parameters of the drug. One of the correlation characteristics of mass transfer is the assessment of the permeability coefficient for a specific membrane that simulates skin. Permeability coefficient describes the rate of penetration of a drug per unit concentration in distance/time units. An example of relationship of "structure-permeability" correlation are the equations relating the permeability constant and lipophilicity to the molecular weight of the drug. The paper showed statistical methods of data analysis (MANOVA, ANOVA) and model-dependent methods (zero order, first order, Higuchi model, Korsmeyer – Peppas model, Hixson – Crowell model, etc.). The ideal drug delivery of non-degradable and non-disaggregating drugs describes as drug release model by zero-order reaction. For drug release of water-soluble drugs from a porous matrix, first-order reaction model is more typical. Kinetic models of fractional power functions are used usually as the cube root law (Hixson – Crowell model) or the square root law (Higuchi model) to describe the process of drug release from gels and dermal films and patches. The Korsmeyer – Peppas model allows us to evaluate the mechanism of mass transfer with Fickian diffusion or another process.Conclusion. Mathematical modeling of the drug release kinetics from soft dosage forms is an important element for the development and optimization of their compositions. The study of the drugs release from soft dosage forms, including TTS and polymer films, as well as the release from solid dosage forms, is based on establishing correlations between the kinetics of the release and dissolution profile. The main release models, regardless of the DF, remain the following models: zero order, first order, Korsmeyer – Peppas, Higuchi, Hickson – Crowell, the empirical or semi-empirical constants of which vary significantly depending on the DF and the release mechanism (Fickian diffusion or another drug mass transfer mechanism). Correlation relationships QSPeR or QSPR, using the coefficients of permeability, diffusion and lipophilicity, provide information on the mass transfer of drugs through the skin.

Introduction. The introduction of devices – analogues of GIS (hereinafter–- Gastro-intestinal simulator) is one of the current ways to develop in-vitro assessment of the quality of solid dosage forms. Testing on a physiologically relevant test device (hereinafter referred to as PRT) makes it possible to predict pharmacokinetic profiles due to more relevant conditions, including the use of biorelevant dissolution media, physiological volumes of the gastrointestinal tract, as well as transit between them.Aim. Conduct a study of cladribine tablets on a physiologically relevant tester in order to predict the behavior of the drug in the human gastrointestinal tract.Materials and methods. The objects of the study are "Mavenclad®, tablets, 10 mg" (series 2200754, expiration date until 04.2025, NERPHARMA, S.r.L., Italy) and "Cladribine, tablets, 10 mg" of domestic production with valid expiration date. During the study, the reagents necessary for the preparation of biorelevant dissolution media and quantitative determination by HPLC. Physiologically relevant test were carried out using an apparatus of our own production, consisting of a DT-6 dissolution tester (ERWEKA GmbH, Germany), a water bath equipped with a Thermomix WB-4 heating element (B. Braun, Germany), and peristaltic pumps (Kamoer, China). The quantitative content of released cladribine was assessed using a highly efficient liquid chromatograph "Khromatek-Kristall HPLC 2014" (ZAO SKB "Khromatek", Russia) using a validated method at a wavelength of 252 nm, analysis time – 7 min, column – Grace HPLC Column Platinum C18-EPS, 250 × 4.6 mm, 5 mm (Grace, USA), temperature – 35 °C, elution mode – isocratic (A : B 80 : 20), mobile phase A – 0.1 % H3PO4 solution, phase B – acetonitrile.Results and discussion. Profiles were obtained to assess the dynamics and degree of release of the studied drugs in various parts of the human gastrointestinal tract. Despite the expected degradation of cladribine in an acidic environment (pH1.2), under physiologically relevant conditions, the drug reached the third section (small intestine model) without degradation. Complete release of cladribine from the test and reference dosage forms was observed. Also, in the future, based on the data obtained, it is possible to predict pharmacokinetic profiles using physiologically based pharmacokinetic modeling approaches.Conclusion. A PSF study was conducted for the drugs "Mavenclad®, tablets, 10 mg" and "Cladribine, tablets, 10 mg". Quantitative determination was carried out by HPLC-UV method. The test results showed complete release of both drugs and reaching the intestinal tract, indicating the absence of degradation of cladribine in the region simulating the stomach.

Introduction. The most important stage of pharmaceutical development of a generic drug is a clinical trial involving humans – a bioequivalence study. Considering the importance of finding rivaroxaban drugs in the list of vital and essential drugs, as part of ensuring technological sovereignty, the use of scientific robust and effective methods for determining the quality of the dosage form is required.Aim. Conduct a study of rivaroxaban tablets on a physiologically relevant tester to predict pharmacokinetic profiles.Materials and methods. The objects of the study are "Xarelto®, film-coated tablets, 10 mg" (series BXJS871, with an expiration date of October 31, 2024, Bayer AG, Germany), "Xarelto®, film-coated tablets, 20 mg" (series BXKDF32, with an expiration date of May 17, 2026, Bayer AG, Germany) and "Rivaroxaban, film-coated tablets, 10 mg" and "Rivaroxaban, film-coated tablets, 20 mg", domestically produced, with valid expiration dates. During the study, reagents were used to prepare dissolution media and perform quantitative determination. The physiologically relevant test was performed on the SC PRT-6 device (LLC "Scientific Compliance", Russia). The quantitative content of released rivaroxaban within the comparative dissolution kinetics test in a medium of 0.1 in a medium of 0.1 % sodium lauryl sulfate solution in a phosphate buffer solution pH 6.5 was carried out on a SF-2000 spectrophotometer (LLC "OKB Spektr", Russia). The quantitative content of released rivaroxaban within the comparative dissolution kinetics test in biorelevant dissolution media and physiological relevance test was assessed on a high-performance liquid chromatograph "Chromatec-Crystal HPLC 2014" (CJSC "Chromatec", Russia). Pharmacokinetic profiles were modeled in the PK-Sim® (Systems Biology Software Suite 11.2, Bayer Technology Services GmbH, Germany) program based on the data obtained within the physiologically relevant test. The clinical study of rivaroxaban tablets was a prospective, open-label, randomized, crossover, two-stage comparative study in two groups of volunteers with a single dose of drugs on the fast condition. The study randomized 30 healthy male volunteers aged 18–45 years.Results and discussion. A complex of in vitro tests was conducted, profiles were obtained that allow us to evaluate the dynamics and degree of release of the studied drugs in various parts of the human gastrointestinal tract. A comparison of the sequential and hybrid schemes for conducting the physiological relevance test was carried out. Within the framework of the set of tests, qualitative and quantitative correlation with the clinical trials data was observed only for the hybrid physiological relevance test scheme. Based on the results of physiological relevance test using different schemes, pharmacokinetic profiles for a pair of drugs were predicted and the prediction error was assessed.Conclusion. A set of scientific in vitro tests was conducted for the drugs "Xarelto®, film-coated tablets, 10 mg and 20 mg", "Rivaroxaban, film-coated tablets, 10 mg and 20 mg". Based on the physiological relevance test results, pharmacokinetic profiles for a pair of drugs were predicted with low error and high reliability. As part of the comparison of data obtained during clinical trial and modeling, the smallest prediction error was noted when performing physiological relevance test using a hybrid scheme.

On 15 June 2024, Alexey Ivanovich Slivkin, the head of the Department of Pharmaceutical Chemistry and Pharmaceutical Technology of the Faculty of Pharmacy, Voronezh State University, Professor, Doctor of Pharmaceutical Sciences, Honored Worker of Higher Education of the Russian Federation turns 80 years old.

Introduction. Dissolving polymeric microneedles are attractive drug delivery system especially for vaccine delivery. Still there are a lot of obstacles in developing scalable manufacturing process of them.Aim. To develop a scalable manufacturing process for producing polymeric dissolving microneedles, which can enable keeping protein activity during manufacturing process.Materials and methods. Microneedles were produced from aqua solution of 20 % w.v. pullulan and 3 % w.v. polyvinyl alcohol by casting in hollow negative polyethylene terephthalate mold. Human serum albumin was chosen as a model protein for this investigation.Results and discussion. There were chosen the mode of mold filling and microneedle drying process, which can guarantee keeping of protein activity during manufacturing process.Conclusion. The designed technology can be easily scaled up and used for producing vaccine drug delivery systems, because it doesn’t contain any restraining processes.

Introduction. Darunavir as an effective antiretroviral drug is widely used in clinical practice, including for the treatment of pediatric patients, as well as pregnant women, and for personalized therapy. Currently darunavir is used in the production of finished dosage forms, both in the form of crystalline ethanolate and in the form of an amorphous substance. In this regard, there is a need to develop and improve methods for the quantitative determination of darunavir. As an inexpensive and effective alternative to common chromatographic and titrimetric methods, spectrophotometric determination of darunavir in the ultraviolet region of the spectrum (UV spectrophotometry) may be used.Aim. To develop and validate a method for the quantitative determination of amorphous darunavir in the substance by UV spectrophotometry.Materials and methods. The following substances and consumables were used for the research: powdered amorphous darunavir substance (USP); darunavir reference standard (MSN Pharmachem Pvt. Ltd., India); methanol for HPLC Gradient Grade 99.9 % (High purity); acetonitrile for HPLC Gradient Grade 99.9 %; glacial acetic acid for HPLC; 0.1 M perchloric acid solution (in anhydrous acetic acid) for titration in non-aqueous media; nylon syringe filters with a pore diameter of 0.22 microns. Spectrophotometric determination of darunavir was carried out using an Cary 60 spectrophotometer (Agilent Technologies, USA) and a UNICO 2800 spectrophotometer (United Products & Instruments, Inc., USA). To prepare standard solutions, we used analytical balance Analytical Balance MS105/A (METTLER TOLEDO, Switzerland), analytical balance GH-120 (AND, Japan) class A measuring glassware, graduated pipettes ISOLAB.Results and discussion. The method was developed and validated for the following characteristics: specificity, linearity, accuracy, precision, analytical range. According to the study results, the main validation characteristics of the method meet the acceptance criteria.Conclusion. A new method for the quantitative determination of amorphous darunavir by UV spectrophotometry was successfully developed and validated. The method may be used to control the quality of substances of amorphous darunavir, including the intrapharmaceutical control.

Pharmaceuticals and medicines play an important role in maintaining human health. However, like any other products, they may contain potentially dangerous substances the so-called genotoxic impurities which can harm human health when consumed, so quality control of pharmaceutical products is of particular importance. Genotoxicity is the ability of a substance to have an irreversible effect on the structure and functions of DNA in cells thereby causing DNA death and errors in its replication, mutations and chromosomal aberrations. One of these substances is N-nitrosamines, which are formed as a result of the interaction of secondary amines with nitrites or nitrates. The Labconcept Group is the official distributor of leading manufacturers of analytical and general laboratory equipment. The Labconcept offers comprehensive solutions for equipping laboratories of various fields, including for the pharmaceutical industry. In this article, we will consider the possibility of determining such impurities using the EXPEC G-Chrom MS triple quadruple gas mass spectrometer using N-nitrosamines as an example.

Introduction. Determination of pesticide residues presence in herbal plants and preparations based on them is an important step in confirming safety at the stage of the quality control of herbal plants. The usage of organophosphate pesticides (OPs) for the purposes of treatment of medicinal plants in the growing process is increasing. Scientific sources provide information on the detection of OPs in herbal plants, including quantities exceeding the allowed percentage limits as it is settled in regulatory documentation. At the same time, the problem of the distribution of particular kinds of OPs in the organs of herbal plants and their persistence remains understudied.Aim. The present research aims to study the distribution in various parts of the herbal plants (marigolds, valerian, and stinging nettle) and the persistence of malathion and diazinon.Materials and methods. Stinging nettle, that grows everywhere, exclusively cultivated marigolds, and valerian were selected as model plants. All of the plants were divided into three equal groups. Young plant shoots were processed twice with "Aliot" products containing 570 g/l of malathion and "Terradox" containing 40 g/kg of diazinon. The first group of plants was processed with pesticides following the manufacturer's instructions. The second group was treated in quantities, that were three times higher than the recommended dosage. The third group (control), was not processed with pesticides. Samples of various parts of growing herbal plants were analyzed at certain time points with the HPLC-MS/MS method according to the developed methodology. In order to study the persistence, we carried out a repeated analysis of dried samples stored without access to sunlight 0.5 years after the first one according to the requirements of the State Pharmacopoeia of the Russian Federation XV.Results and discussion. The authors found malathion and diazinon in all of the analyzed parts of medicinal marigolds, in leaves and roots of nettle dioecious, in deciduous shoots and rhizomes with roots of valerian officinalis. The highest proportion of pesticides was discovered in underground plant organs. When processed according to the instructions, in marigold and nettle roots and in rhizomes with valerian roots 16.7 mg/kg, 4.5 mg/kg, and 1.7 mg/kg of malathion and 19.6 mg/kg, 4.1 mg/kg, and 1.5 mg/kg of diazinon were found, respectively. These quantities exceed the allowed limits. The quantity of pesticides in the flowers of medicinal marigolds does not exceed the permissible values. The research on the persistence of these OPs data demonstrates that malathion and diazinon persist in plant tissues for a long time.Conclusion. As a result of the research quantitative characteristics of the distribution of malathion and diazinon in various parts of medicinal marigolds, medicinal valerian, and dioecious nettle, as well as the rate and the extent of degradation of OPs during six months, were determined.

Introduction. The data on the wide clinical use of low-molecular-weight heparin (LMWH) preparations are presented, necessitating the need for efficient and high-quality production of appropriate pharmaceuticals. The revealed variability of anticoagulant activity of LMWH preparations implies the provision of production with validated methods of control and certification. The aim of the work is to study the possibility of control of anticoagulant activity and assessment of functional compatibility of LMWH preparations when using domestic test systems.Text. The data on analytical characteristics of chromogenic and coagulometric methods performed with the help of domestic test systems are presented. Their parameters correspond with the existing international requirements. The possibility of the mentioned methods to certify LMWH preparations correctly and reproducibly is shown. The given research results testify to the possibility of clotting methods to determine the bioequivalence of the studied preparations of LMWH.Conclusion. The presented data prove the expediency of production control and certification of LMWH preparations by domestic test systems.

We present to your attention a new interview as part of the Leaders' Opinion series. Thenext guests of the series were the creators of the apparatus for conducting a physiologically relevant test General Director of LLC "CPHA", editor-in-chief of the journal "Drug development & registration", Doctor of Pharmaceutical Sciences Igor E. Shokhin and General Director of LLC "Scientific Compliance" Andrey M. Poluyanov.

Introduction. Deferasirox is a complexing drug and belongs to class II according to the biopharmaceutical classification system (BCS), has acidic properties and belongs to subclass “a” (acid). This class is characterized by high permeability and low solubility, which limits the absorption of the active substance into the blood. As a result, the development of drugs with an active substance that can be assigning BCS to this class is a difficult task, and for generic drugs it is also associated with a high risk of obtaining unproven equivalence during clinical trials. To minimize the above risks, a physiologically relevant test was carried out with further data processing and construction of putative pharmacokinetic profiles.Aim. The aim of the study is to conduct a physiologically relevant test (PRT) to predict in vitro pharmacokinetic profiles and compare them with in vivo data as part of a bioequivalence study of deferasirox.Materials and methods. The objects of the study are "Deferasirox, film-coated tablets, 360 mg" of a domestic manufacturer and "Jadenu®, film-coated tablets, 360 mg" (WTN22 series, expiration date until 10.2023, Novartis Pharma Stein AG, Switzerland). A physiologically relevant test was performed on the device SC PRT-6, Compliance. Quantitative analysis was carried out by HPLC-UV method.Pharmacokinetic profiles were modeled using PK-Sim® (Systems Biology Software Suite 11.2, Bayer Technology Services GmbH, Germany) based on data obtained from physiologically relevant test.Results and discussion. A physiologically relevant drug test for deferasirox was performed and release profiles were obtained, which formed the basis of a physiologically based pharmacokinetic model together with data on the physicochemical properties of the studied compound and literature data on the pharmacokinetics of deferasirox. The pharmacokinetic profiles obtained as part of the simulation on a virtual population were compared with data obtained during clinical trials.Conclusion. A physiologically relevant test for the drug deferasirox was carried out, quantitative determination in the samples was carried out by HPLC-UV. The test resulted in data that allowed prediction of pharmacokinetic profiles that reflected the same differences observed in the profiles of the test and reference drug in the comparative pharmacokinetics and bioequivalence study of deferasirox drugs.

Introduction. Sorafenib is an antineoplastic drug belonging to class IIc according to the biopharmaceutical classification system (BCS) due to the presence of both acidic and basic properties. In addition to low solubility, sorafenib is characterized by high variability during clinical trials, in particular bioequivalence studies (BE). To selecting batches that can be recommended for BE studies, the dissolution kinetics test is currently widely used, however, the results of this test are not always sufficient and additional tests, for example, a physiologically relevant test, are advisable. To minimize the risks of obtaining nonequivalent results during the BE study, a physiologically relevant test (PRT) was carried out with further data processing and interpretation of the results of physiologically based pharmacokinetic modeling (PBPK).Aim. The aim of the study is to conduct a physiologically relevant test (PRT) for the purpose of selecting a candidate batch for subsequent BE study of sorafenib drugs using the physiologically based pharmacokinetic model (PBPK).Materials and methods. The objects of the study are Nexavar®, film-coated tablets, 200 mg (Bayer AG, Germany) (one batch) and Sorafenib, film-coated tablets, 200 mg (two batches) (Russia). The physiologically relevant test was performed on the SC PRT-6 device (LLC "Scientific Compliance", Russia). Quantitative analysis was performed by HPLC-UV on the Chromatec-Crystal HPLC 2014 device (CJSC "Chromatec", Russia). The plasma concentration profiles were simulated using PK-Sim® software (Systems Biology Software Suite 11.2, Bayer Technology Services GmbH, Germany).Results and discussion. As part of the study, a method for the quantitative determination of sorafenib was developed and validated, a method for sample preparation was developed, and a method for conducting the PRT for sorafenib, as a representative of the IIc subclass of BCS, was developed. Based on the study results, release profiles were obtained that were used to select a candidate series for the BE study. The series were selected based on the PBPK analysis on a virtual population consisting of 36 healthy volunteers with activated enteropathic circulation, characteristic of sorafenib.Conclusion. The PRT was carried out for the drug sorafenib. Quantitative determination was carried out by HPLC-UV according to the developed and validated method. The test resulted in obtaining data that were subjected to PBPK analysis. It was shown that the studied batches have high risks of non-equivalence during the bioequivalence study.

The second part of the article presents the structure of the Apothecary order at the time of its final formation. This publication also focuses on the personnel who served in the organization. The chiefs of the Apothecary order are listed from the moment of its setting up until its final reorganization, as well as the positions of the main and auxiliary personnel. The functions of the Apothecary order, which are traditionally divided into palatial and state, are analyzed. The first ones include medical, veterinary, purveyance, horticultural, expert and production functions. The state ones are constabulary-medical, military-medical, educational and administrative functions. The particular interest consists in the special function of the Apothecary prikaz – the collection, storage and study of scientific works on medicine.

In the final phases of bacterial cell wall synthesis, penicillin-binding proteins (PBPs) catalyze the cross-linking of peptidoglycan. For many decades, effective and non-toxic β-lactam antibiotics have been successfully used as mimetics of the d-Ala-d-Ala moiety of the natural substrate and employed as irreversible inhibitors of PBPs. In the years following their discovery, the emergence of resistant bacteria led to a decline in their clinical efficacy. Using Staudinger cycloaddition, we synthesized a focused library of novel monocyclic β-lactams in which different substituents were introduced at the C4 position of the β-lactam ring, at the C3 amino position, and at the N1 lactam nitrogen. In biochemical assays, the compounds were evaluated for their inhibitory effect on the model enzyme PBP1b from Streptococcus pneumoniae. Upon investigation of the antibacterial activity of the newly prepared compounds against ESKAPE pathogens, some compounds showed moderate inhibition. We also examined their reactivity and selectivity in a biochemical assay with other enzymes that have a catalytic serine in the active site, such as human cholinesterases, where they also showed no inhibitory activity, highlighting their specificity for bacterial targets. These compounds form the basis for further work on new monocyclic β-lactams with improved antibacterial activity.

The formulation of biopharmaceutical drugs is designed to eliminate chemical instabilities, increase conformational and colloidal stability of proteins, and optimize interfacial stability. Among the various excipients involved, buffer composition plays a pivotal role. However, conventional buffers like histidine and phosphate buffers may not always be the optimal choice for all monoclonal antibodies (mAbs). In this study, we investigated the effects of several alternative buffer systems on seven different mAbs, exploring various combinations of ionic strengths, concentrations of the main buffer component, mAb concentrations, and stress conditions. Protein stability was assessed by analyzing soluble aggregate formation through size exclusion chromatography. At low protein concentrations, protein instability after temperature stress was exclusively observed in the bis-TRIS/ glucuronate buffer. Conversely, freeze-thaw stress led to a significant increase in aggregate formation in tested formulations, highlighting the efficacy of several alternative buffers, particularly arginine/ citrate, in preserving protein stability. Under temperature stress, the introduction of arginine to histidine buffer systems provided additional stabilization, while the addition of lysine resulted in protein destabilization. Similarly, the incorporation of arginine into histi-dine/HCl buffer further enhanced protein stability during freeze--thaw cycles. At high protein concentrations, the histidine/citrate buffer emerged as one of the most optimal choices for addressing temperature and light-induced stress. The efficacy of histidine buffers in combating light stress might be attributed to the light-absorbing properties of histidine molecules. Our findings demonstrate that the development of biopharmaceutical formulations should not be confined to conventional buffer systems, as numerous alternative options exhibit comparable or even superior performance.

Lenvatinib is an orally effective tyrosine kinase inhibitor used to treat several types of tumors, including progressive, radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma. Although this drug is increasingly used in therapy, its metabolism and effects on the organism are still not described in detail. Using the rat as an experimental animal model, this study aimed to investigate the metabolism of lenvatinib by rat microsomal enzymes and cytochrome P450 (CYPs) enzymes recombinantly expressed in SupersomesTM in vitro and to assess the effect of lenvatinib on rat CYP expression in vivo. Two metabolites, O-desmethyl lenvatinib, and lenvatinib N-oxide, were produced by rat CYPs in vitro. CYP2A1 and 2C12 were found to be the most effective in forming O-desmethyl lenvatinib, while CYP3A2 was found to primarily form lenvatinib N-oxide. The administration of lenvatinib to rats caused changes in the expression of mRNA and protein, as well as the activity of various CYPs, particularly in an increase in CYP1A1. Thus, the administration of lenvatinib to rats has an impact on the level of CYPs.

Polyurethane/hydroxyapatite (PU/HA) composites are well-known for various biomedical applications. This study reports a chemical approach to improve the interaction between HA and PU matrix. HA was surface-modified with 1,6-hexamethylene diisocyanate (HMDI). First, an isocyanate-modified HA (IHA) was synthesized by hydro-thermal method. Second, IHA was incorporated into a separately synthesized thermoplastic PU by a solvent casting technique. A series of PU/IHA composites was prepared by varying PU᾿s soft and hard segments. The IHA was added to PU (5 and 10 %). The FTIR spectra exhibited characteristic bands of urethane and HA, confirming the synthesis of the composites. XRD study showed the crystallite size of IHA (20 Å) with hexagonal geometry and an amorphous to semicrystalline nature of composites. SEM showed that composites displayed porous and granular morphology. The TGA thermograms of the composites revealed the thermal stability up to 400 °C. The IHA addition considerably improved hydrophilicity and degradation of the composites in simulated body fluid (SBF). MTT assay revealed improved cytocompatibility (> 80 %) of the composites. These results demonstrated an appreciable improvement in structure, morphology, hydrophilicity, degradation, and cytocompatibility of PU/IHA composites by chemical modification of HA. Hence, these composites possess remarkable potential for biomedical applications such as tissue regeneration.

A new micellar electrokinetic capillary chromatographic (MEKC) method has been developed and optimized for simultaneous quantitation of doxorubicin (Dox) and fullerenol (Frl) in rat serum. The separation was carried out in a capillary (48.5–40 cm to the detector – 50 µm id fused-silica capillary with bubble cell, 150 µm) at an applied voltage of 25 kV and temperature of 25 °C. For the background electrolyte 10 mmol L–1 borate buffer pH 9.3 plus 15 mmol L–1 phosphate buffer pH 7.0 (with the final pH of the mixture adjusted to 7.0 with HCl), with added 10 % (V/V) methanol, and 15 mmol L–1 sodium dodecyl sulfate as a surfactant, were used. The hydrodynamic injection was carried out at 5.0 kPa during the period of 100 s. Linear calibration curves were established over the concentration range 0.5–500.0 mg L–1 for Dox and 10.0–500.0 mg L–1 for Frl (at 234 nm). The proposed MEKC procedure was fully validated and applied for the deter mination of Dox and Frl in Wistar rats after intra pe ritoneal administration of both molecules.

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 μmol L–1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.

This meta-analysis aimed to evaluate the efficacy of sorafenib plus transcatheter arterial chemoembolization (TACE) in treating hepato-cellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Twelve randomized controlled trials published until 28th Sep 2022 were finally included. Of the total 1746 patients, of whom 458 received sorafenib and TACE treatment (Group S+TACE), and 1288 only underwent TACE (Group TACE), were enrolled. Outcomes including time to progression (TTP), objective response rate (ORR), disease control rate (DCR), overall survival (OS), survival rate (SR), and adverse reactions, were extracted. The OS (HR: 0.596, 95 %CI: 0.507–0.685, p < 0.001; I2 = 0.0 %) and TTP (HR: 0.379, 95 %CI: 0.205–0.553, p < 0.001; I2 = 4.5 %) in the S+TACE group were longer than those in the TACE group. The ORR (RR: 2.101, 95 %CI: 1.555–2.839, p < 0.001; I2 = 0.0 %), DCR (RR: 1.547, 95 %CI: 1.126–2.126, p = 0.007; I2 = 79.6 %) and SR (RR: 1.416, 95 %CI: 1.183-1.694, p < 0.001; I2 = 83.8 %) in the S+TACE group were higher than those in the TACE group. Compared with the TCAE group, the higher odds of HFSR, oral ulcer, and diarrhea among patients with HCC complicated by PVTT were discovered in the S+TACE group. The marginal significance was found in ascites and gastrointestinal bleeding between the two groups. Sorafenib plus TACE has good efficacy and mild adverse reactions, which may be worthy of clinical promotion.

Dry eye disease (DED) is an ocular condition characterized by altered tear film homeostasis, resulting in symptoms like tear film instability, hyperosmolarity, inflammation, and neurosensory abnormalities. It affects visual acuity and quality of life and is influenced by age, gender, and environmental factors. The first line of treatment consists of dynamically developing artificial tears, gels, and eyelid sprays, which can be supplemented with natural ingredients for enhanced efficacy. Other therapeutic steps include auto-logous serum tears, anti-inflammatory and immunosuppressive eyedrops, or oral tablets. Management also targets Meibomian gland dysfunction and the ocular surface micro-biome. This article explores various therapeutic approaches, including natural compounds and complementary strategies. Natural compounds, such as vitamins, and herbal substances (e.g., trehalose), offer promising benefits in enhancing tear film stability and ocular surface protection. Apitherapeutic products like manuka honey and propolis exhibit antibacterial and anti-inflammatory properties. Additionally, human tissue-derived solutions, such as auto-logous serum tears and amniotic membrane extracts, hold the potential for ocular surface regeneration. Other strategies, including polyherbal eye drops, liposomal eyelid sprays, and microbiome-supporting solutions offer alternative therapeutic avenues. Moreover, patient education, lifestyle modifications, and interdisciplinary collaboration play crucial roles in DED management, emphasizing the importance of holistic care approaches.

Despite great therapeutic advances in the field of biologics, small synthetic molecules such as thiopurines, including azathioprine, mercaptopurine, and thioguanine, remain an important therapeutic pillar in the treatment of inflammatory bowel disease, other autoimmune disorders, and cancer. This review presents the latest guidelines for thiopurine administration, highlighting the importance of individualized therapy guided by pharmacogenomics. It emphasizes dose adjustment based on nudix hydrolase 15 (NUDT15) and thiopurine S-methyltransferase (TPMT) genotype, along side thiopurine S-methyltransferase activity and thiopurine metabolic profile. In addition, the article takes a critical look at emerging research in the field of thiopurine pharmaco genomics featuring novel genetic markers and technological developments in genetic testing. Finally, the potential of integrated approaches that combine genetic, meta bolic, and clinical factors to further individualize thiopurine therapy is highlighted.

Reliable gene expression analysis in bone remodeling studies requires an appropriate selection of internal controls, i.e. stable reference genes for the normalization of quantitative real-time PCR (RT-qPCR), the most common method used for quantifying gene expression measurements. Even the most widely used reference genes can have variable expression under different experimental conditions, or in different tissue types or treatment regimes, so selecting appropriate controls is a key step in ensuring reliable results. The aim of this research was to identify the most stable reference gene(s) for the study of olanzapine modulated bone remodeling in rats. RNA was isolated from the maxillary alveolar and femoral bones of olanzapine or placebo-treated Wistar rats and transcribed to cDNA. The expression of 12 candidate reference genes was assessed by RT-qPCR. Their expressions were analysed using GeNorm, NormFinder, BestKeeper and delta Ct algorithms, and by the comprehensive ranking method. PPIA, HRPT1 and PGK1 were the most stably expres sed reference genes and the combination of the three genes was optimal for normalization. This study is the first to identify the optimal reference genes for research in olanzapine-exposed rats, which serve as a pivotal benchmark for enhancing the accuracy and reliability of future RT-qPCR expression in bone studies.

Prostate cancer is a significant global health concern that requires innovative therapeutic investigations. Here, the potential anticancer properties of tannic acid were evaluated by examining its effects on apoptosis in prostate cancer cell lines. PC-3 and LnCaP prostate adeno carcinoma cells, along with PNT1A prostate control cells, were cultured and divided into untreated and tannic acid-treated groups. Cell proliferation, cytotoxicity, and effects of tannic acid on the cell death mechanism were evaluated. mRNA expression levels of 84 genes were explored in cells following tannic acid treatment. Notably, tannic acid-induced down-regulation of several pro-survival genes, including ATM, BCL2, BCL2A1, BIK, BIRC2, BIRC3, BRE, CASP3, CASP6, CASP8, CHEK2, CRADD, PPIA, RPA3, TNFSF18, TRAF1, TRAF2, TRAF4, and TRAF5 in both cell lines. Moreover, tannic acid treatment led to the up-regulation of various pro-apoptotic genes, such as BCL10, BIRC3, BNIP3, CASP1, CASP5, CD40, CIDEB, DAPK2, FASLG, GADD45A, MYD88, RPA 3, TNFRSF10D, TNFRSF17, TNFRSF8, TNFSF13B, TNFSF4, TNFSF7, TNFSF8, TNFSF9, TP53, TRAF1, and TRAF2 in both PC-3 and LnCap cells. These findings highlight tannic acid’s ability to induce apoptosis in prostate cancer cells through pro-apoptotic pathways. This study concludes that tannic acid selectively inhibits prostate cancer cell growth.

PRT is a unique high-tech scientific installation of domestic production, which, among other things, implements the ideas of the foreign scientific apparatus GIS (Gastro Intestinal Simulator). Our device allows us to study the behavior of a tablet or capsule under conditions close to real ones for the human gastrointestinal tract, and based on the data obtained during the test, predict pharmacokinetic profiles.

The 9TH Pan-Russian GMP conference with international participation was held on August 21–23 in the capital of the Republic of Bashkortostan – Ufa. This year's motto is "GMP – continuous development".

Introduction. The use of tofacitinib as a pharmacological treatment for rheumatoid arthritis remains relevant in the light of the predicted increase in prevalence of the disease. At the same time, due to the withdrawal of several foreign pharmaceutical companies from the Russian pharmaceutical market, there has been a heightened demand for domestically produced medications, including generic formulations of tofacitinib. Registration of generic drugs necessitates the conduct of bioanalytical studies. Development and validation of a method for quantifying the analyte in biosamples remains to be a crucial part of the bioequivalence studies.Aim. The aim of this research is to develop and validate a method for the quantitative determination of tofacitinib in human plasma using high-performance liquid chromatography as the separation system coupled with a tandem mass spectrometer for detection purposes.Materials and methods. Biosample preparation was based on plasma proteins precipitation using acetonitrile. Baricitinib was selected as an internal standard. The analytical range of the method was 1.00 to 200.00 ng/mL and was further expanded to 0.30 to 200.00 ng/mL during the analytical phase of the study. The mobile phase consisted of water and acetonitrile, both acidified with formic acid (0.1 % v/v). The stationary phase was a Phenomenex Kinetex C18 column [100 × 3.0 mm, with a particle size of 5 µm (Phenomenex, USA)]. Sample separation and detection were carried out using high-performance liquid chromatography coupled with a tandem mass spectrometry (HPLC-MS/MS), operating in positive ion mode. The multiple reaction monitoring (MRM) transitions selected for the analyte and the internal standard were 313.30 to 173.00 m/z and 371.90 to 186.00 m/z, respectively.Results and discussion. The developed assay was validated in accordance with the current requirements of regulatory documentation from the EAEU (Eurasian Economic Union), FDA (US Food and Drug Administration), and EMA (European Medicines Agency) with the following parameters being evaluated: selectivity, specificity, carry-over, matrix effect, recovery, calibration curve, lower limit of quantitation, accuracy, precision, stability. The validated method was applied in the analytical part of a bioequivalence study of domestically produced generic tofacitinib.Conclusion. A method for the quantitative determination of tofacitinib in human blood plasma with an analytical range of 0.30–200.00 ng/mL was developed and validated. Application of the assay during the analytical phase of bioequivalence study of generic tofacitinib confirms the possibility of using the method in similar bioanalytical investigations.

Introduction. Search for new plant species containing biologically active substances (hereinafter – BAS) is one of the leading tasks of pharmacognosy as a science. The search for flavonoid glycosides in plant raw materials is especially relevant, since they have anti-inflammatory, antioxidant, immunostimulating, as well as weak fungicidal and bacteriostatic action. Staphylea pinnata L. is an endemic plant of the Caucasus, cultivated not only in Georgia, but also in the Russian Federation in the Northern and Northwestern Caucasus. In foreign literature there are studies of antioxidant, antiproliferative and cytotoxic activity of leaf extracts of several species of S. pinnata L., as well as inhibitory activity of COX-1, COX-2 and LTB4 formation. Meanwhile, no serious Russian-language scientific studies on either the chemical composition or pharmacological action of generative organs of S. pinnata were found in the literature. This work is part of a comprehensive phytochemical study of S. pinnata. The aim of the work is to study the qualitative and quantitative composition of flavonoids in the studied object.Aim. To isolate, identify and quantify flavonoids in flowers and buds of Staphylea pinnata L.Materials and methods. Alcohol-water extracts from dried generative organs of the studied plant were used as analyzed solutions. Solutions were analyzed on a spectrophotometer SF-2000 (LLC "OKB Spectr", Russia) after sample preparation with aluminum chloride and on an HPLC Nexera-i LC-2040 (Shimadzu Corporation, Japan) equipped with a column and sample thermostat, degasser and autosampler using an individually selected elution gradient of the mobile phase (0.1 % orthophosphoric acid/acetonitrile solution). The primary data were processed using LabSolutions Single LC software (Shimadzu Corporation, Japan). Compounds from the flavonoid group were identified by retention times. Detection was carried out using a UV detector with an absorption wavelength of 365 ± 2 nm.Result and discussion. Alcohol-water extracts from flowers and buds of S. pinnata L. were obtained. Quantitative evaluation by spectrophotometry for flavonoid content was carried out. A gradient elution mode for HPLC was selected for simultaneous determination of 7 flavonoid glycosides. These chromatographic conditions allowed the identification and quantification of astragaline, cynaroside, cosmosiin, narcissin and rutin in flowers and buds of Staphylea pinnata L. Flavonoid glycosides: raponticin and kaempferol were not detected.Conclusion. Flavonoid glycosides were isolated from the generative organs of S. pinnata L., a technique for quantitative determination of flavonoid glycosides in alcohol-water extracts was developed, astragalin, cynaroside, cosmosiin, narcissin and rutin were detected and quantified.

Introduction. Virgin grape (maiden grape, Virginia grape, virgin grape, Parthenocissus quinquefolia (L.) Planch.) is currently used primarily for decorative purposes, but is also beginning to attract scientists from different countries as a promising source of important compounds such as anthocyanins, flavonoids, organic acids, macro- and microelements. To introduce a plant into medical practice, one of the first steps is the need to develop regulatory documentation that allows for quality assessment and standardization of plant materials, and the first stage of this process is the assessment of the characteristics of the authenticity of the object.Aim. Establish the morphological characteristics of the leaf and petiole of the virgin grape (Parthenocissus quinquefolia (L.) Planch.).Materials and methods. The object of the study was developed leaves of the virgin grape, harvested in the Voronezh region in the summer of 2022 and dried in the shade. To carry out the experiment, a JSM-6510LV electron microscope was used; the analysis was carried out after sputtering a thin film of gold onto the sample.Results and discussion. For the first time, the main structural features of various morphological features of the leaf blade of the virgin grape were identified, differences in the morphological picture of the upper and lower sides of the leaf were established, and structural features of the surface of the petiole were identified. Using micro-X-ray analysis, it was revealed that calcium and potassium are present in large quantities in the leaves and petiole of virgin grapes. The least amount of the studied elements in the study object contains magnesium. It has been shown that the leaves contain a small amount of chlorine, and the cellular contents of the petiole include a small amount of sodium.Conclusion. For the first time, a study of the morphology of the surface of the leaf blade and petiole of the virgin grape was carried out using scanning electron microscopy. The main diagnostic features of plant raw materials have been identified and visualized. Micro-X-ray structural analysis made it possible to establish the composition of the elements of the leaf blade and petiole of virgin grapes and revealed the ability to concentrate calcium, potassium, and phosphorus.

Introduction. Medicines of natural origin have advantages over synthetic drugs and occupy a significant share in the assortment of pharmacies. Filipendula ulmaria (L.) Maxim., characterized by a chemical composition rich in phenolic compounds and various types of biological activity has the potential in terms of the development of new herbal medicines. In an in vivo experiment, F. ulmaria extract showed immunomodulatory, anti-inflammatory, osteogenic activity and effectively stimulated myelopoiesis in conditions of microbial damage of bone tissue.Aim. Development of an optimal technology for obtaining dry extract of F. ulmaria by remaceration and investigation of its аcute toxicity.Materials and methods. The technology of extract was developed in a laboratory reactor equipped with a water heater jacket and a stirrer. The content of flavonoids was determined by differential spectrometry. Flowability was determined on a flowability tester for powders and granules, bulk density was determined on a bulk density tester for powders and granules, moisture content was developed on a moisture content analyzer. Acute toxicity was determined on Wistar rats.Results and discussion. The dry extract of F. ulmaria, obtained using 70 % ethanol by remaceration, is effective in conditions of microbial damage of bone tissue and bone marrow, which determined the choice of extragent and the type of extract. The optimal parameters for obtaining the extract were determined (three-fold maceration at a water jacket temperature of 80 °C, the ratio of raw materials to extragent 1 : 14, time 30 min), its main technological characteristics were determined and a wet granulation method for improving them was proposed. In the study of acute toxicity of the extract, according to the results of toxicometry for 14 days after administration and necropsy data, the studied extract was classified as low-toxic substance.Conclusion. The dry extract of F. ulmaria, obtained by remaceration using 70 % ethanol, has specific activity in conditions of microbial damage to bone tissue. Optimal extraction parameters allow to increase the yield of target components, it is advisable to improve the technological parameters of the extract by wet granulation. The assessment of the safety profile of the dry extract from F. ulmaria, along with its high biological activity, provides a perspective for its further study and implementation into medical practice.

Introduction. Currently, there is an increasing trend towards assessing the full spectrum of chemical compounds in plant materials. One of the first steps in the formation of secondary metabolites of complex structure, participating in biochemical processes in the plant body, which have their own effect on the human and animal body, are organic acids (OA) and amino acids (AA). However, due attention is not always given to these compounds when studying the component composition of plant raw materials.Aim. The purpose of the work was to study the profile and quantitative assessment of the content of organic acids and amino acids of Aesculus hippocastanum L. flowers.Materials and methods. The object of the study were horse chestnut flowers, collected during flowering in the Voronezh region in 2021 and dried by air-shade method. Quantitative assessment of the amount of TC in terms of malic acid and ascorbic acid was carried out titrimetrically according to the methods presented in the State Pharmacopoeia of the Russian Federation, XIV edition. The composition of the OA and AA profiles of horse chestnut flowers was determined using the capillary electrophoresis method ("Kapel®-105/105M", Group of Companies "Lumex", Russia).Results and discussion. The method of capillary electrophoresis revealed the presence of 12 compounds of the OA group in a total amount of 4.7 % (in terms of absolutely dry raw materials). The rationality of recalculating the content of the sum of OA to the major component – citric acid, which amounted to 1.65 ± 0.04 %, was shown. The content of ascorbic acid was low (0.033 ± 0.007) %. Using the TLC method, the presence of 5 zones of compounds belonging to the AA class was established in the aqueous extract of horse chestnut flowers. The quantitative content of the sum of free AA in terms of glutamine, determined by the spectrophotometric method, was 2.25 ± 0.07 % (n = 5). The presence of 17 AA was determined by capillary electrophoresis, which amounted to 7.13 %. Glutamic acid is present in the greatest quantity in horse chestnut flowers (1.19 %). Essential amino acids amounted to 2.27 %; leucine was present in the predominant amount (0.58 %).Conclusion. A study was carried out of the qualitative composition and quantitative content of organic acids and amino acids of horse chestnut flowers. The composition of the profile and the quantitative content of organic acids and amino acids have been established. It was revealed that citric acid prevails in the total organic acids; glutamic, aspartic acid, arginine and proline are found in greater quantities in the total amino acids.

Introduction. Yellow wood anemone (Anemone ranunculoides L.) is a herbaceous perennial. This plant grows in the European parts of Russia, Ciscaucasia, Siberia, Central Europe and other regions. It has many different pharmacological activities: immunomodulatory, sedative, anti-inflammatory, antitoxic, diuretic, antibacterial, antioxidant, antitumor and antirheumatic activity. These various effects are due to their biologically active compounds, which include ephemeroids, protoanemonin, saponins, tannins, resins, ascorbic acid, ranunculin, oils lipids and triterpene glycosides. As to phenolic compounds, currently there is no sufficient information on flavonoids and hydroxycinnamic acids (HCAs) profiles in different species of genus Anemone. Because these groups of compounds are quite specific for yellow wood anemone, their detailed study seems to be relevant.Aim. The objective of this research is to identify and quantify flavonoids, HCAs, and their conjugates in Yellow wood anemone leaves, flowers and rhizomes with roots.Materials and methods. The identification was carried out by using ultra-high-performance liquid chromatography with diode array and electrospray ionization-mass spectrometric detection (UHPLC–DAD–ESI-MS) with quantification of individual compounds by external calibration method.Results and discussion. Among the 47 compounds, 30 flavonoids and 17 derivatives of HCAs were detected. Quercetin glycosides were found to be the major flavonoids in aerial parts whereas chalcone glycosides – in underground parts. The major HCA in rhizomes with roots was feruloyltartaric acid (1.18 mg/g) whereas chlorogenic acid was predominant in leaves and flowers (8.68 mg/g and 2.62 mg/g accordingly). The total content of phenolic compounds was estimated at 60 mg/g on a dry weight basis.Conclusion. As a result of the research a detailed profile of flavonoids and HCAs acids of anemon was described. The data obtained can serve to identify this species in the standardization of medicinal plant materials and taxonomic studies.

Introduction. The development of new effective and safe herbal medicines capable of having a positive effect on reproductive status is an urgent task of domestic pharmacy. Medicinal plants are considered as alternative therapies aimed at increasing testosterone levels and fertility in men. The arsenal of medicinal plants used in traditional medicine for the treatment of diseases in men is mainly represented by phytoadaptogens, most of which have a small resource potential in Russia, therefore, it is relevant to search for plants with a sufficient raw material base and with the potential for cultivation. Thlaspi arvense L. is a promising medicinal plant, as it is widely used in folk medicine as a diuretic, anti-inflammatory, diaphoretic, antihistamine, hemostatic, astringent, has a positive effect on the processes of spermatogenesis and is widely distributed in our country. However, information on the chemical composition and biological activity of Thlaspi arvense L. they are insufficient, which shows the relevance of its further more detailed study in order to substantiate the possibility of application in practical medicine and solutions to the issues of standardization of medicinal plant raw materials.Aim. The study of the influence of Thlaspi arvense L. on the characteristics of the reproductive system of male rats.Materials and methods. The object of the study was an infusion of herbа Thlaspi arvense L. The features of the reproductive behavior of male rats after 21-day administration of the infusion of grass yarutka field were studied using tests that allow quantifying the severity of sexual motivation and sexual activity of males. The viability of spermatozoa in the ejaculate of rats was assessed, the total number of spermatozoa (ACS, million), degenerative and immobile forms (%) was calculated. Morphophysiological parameters of spermatogenesis of rats of control and experimental groups of animals were studied using classical histological methods. The concentration of testosterone in the blood serum of experimental groups of animals was determined by the enzyme immunoassay.Results and discussion. The results obtained allow us to conclude that the fertility of rats has increased against the background of the course administration of the infusion of herbа Thlaspi arvense L., as evidenced by an increase in the testosterone content in the blood, improvement of spermogram indicators and morphophysiological characteristics of spermatogenesis in the testicles of rats. The use of the infusion of herbа Thlaspi arvense L. has a protective effect on spermatogenesis. An increase in the thickness of the spermatogenic epithelium, the diameter of the cross-section of the convoluted seminal tubules and the index of spermatogenesis compared with the control group of animals was revealed. The positive effect of Thlaspi arvense L. on indicators of sexual motivation and sexual activity of male rats is shown.Conclusion. Thlaspi arvense L. is a promising medicinal plant, as it is able to have a positive effect on libido, the number and mobility of spermatozoa, the production of sex hormones, spermatogenesis, as well as on the pituitary-gonadal axis, which is associated with the content of a complex of biologically active substances in it.

Introduction. Aronia Мitschurinii (Aronia × mitschurinii A.K. Skvortsov & Maitul) is a species obtained by crossing chokeberry (Aronia melanocarpa (Michx.) Elliott) and mountain ash (Sorbus aucuparia L.). This plant is more widely known in the literature as chokeberry. Mitschurin сhokeberry is actively cultivated in the Russian Federation (RF) and neighboring countries to obtain the main raw material – fruits. Aronia should not be confused with chokeberry, which does not grow wild and is practically not cultivated in the Russian Federation due to the inedibility of the fruit and the low decorative value of the plant. The leaves, unlike the fruits, of Mitschurin chokeberry are not yet used as medicinal plant raw materials (MPR). However, according to preliminary studies, they are a promising source of biologically active substances (tannins, flavonoids, leukoanthocyanins, vitamins, a complex of microelements, etc.), exhibiting astringent, antioxidant and anti-inflammatory activities. Therefore, an urgent task is to develop indicators of the authenticity of raw materials based on the presence of the main groups of biologically active substances, as well as methods and standards for their quantitative content for the formation of draft regulatory documentation for Michurin chokeberry leaves.Aim. The purpose of the study was to study the profile of biologically active substances of Michurin chokeberry leaves, growing in the territory of the Central Black Earth Region of the Russian Federation, to determine the target groups that determine the pharmacological activity of this raw material.Materials and methods. Leaves of Michurin chokeberry for research were harvested during the period of technical maturity of the fruit (August – September 2023) from a plant cultivated in the city of Michurinsk (Tambov region) and dried. Primary screening was carried out for the presence of individual groups of biologically active substances in the leaves of Michurin chokeberry, using known qualitative reactions. The composition of flavonoids was determined by thin layer chromatography. Quantitative determination of the main groups of biologically active substances was carried out according to known methods using modern physicochemical methods of spectrophotometry and capillary electrophoresis.Results and discussion. Tannins, flavonoids, alcohol-soluble saponins, leukoanthocyanins, amino acids, ascorbic acid and polysaccharides in the form of mucilage were found in the leaves of Aronia mitschurinii. No alkaloids were found. TLC analysis of flavonoids revealed at least 4 adsorption zones with yellow-green fluorescence, one of which was identified as rutin. The thiamine content in the leaves was 0.99 ± 0.084 mg/kg; riboflavin – 0.43 ± 0.025 mg/kg; choline – 44.4 ± 3.9 mg/kg; extractives – 31.52 ± 0.22 %; the amount of flavonoids in terms of rutin – 3.48 ± 0.21 %; the amount of tannins in terms of catechin – 8.63 ± 0.32 %; the amount of anthocyanins in terms of cyanidin-3-O-glucoside – 11.62 ± 0.69 %. In the leaves of Aronia mitschurinii, 17 amino acids were identified (total content 5.88 %), 7 of them are essential (2.71 %). The predominant amino acids are leucine and glutamic acid – 18.37 and 10.88 % of the total amino acid content, respectively. The quantitative content of eight free organic acids was also determined (total content 0.49 %). The predominant acids are citric, malic and sorbic.Conclusion. As the target groups of biologically active substances responsible for the pharmacological activity of Aronia mitschurinii leaves, it is most rational to consider a complex of polyphenols (flavonoids, anthocyanin compounds and tannins), the content of which is quite high. According to the spectral characteristics, the dominant biologically active substances in the sum of flavonoids, tannins and anthocyanins are rutin, catechin and cyanidin-3-O-glucoside, respectively. This type of raw material can be considered as a promising source of biologically active substances for the purpose of further obtaining herbal plants preparations with antioxidant, capillary-protective, astringent and anti-inflammatory effects.

Introduction. One of the reasons for the development of many diseases primarily malignant is the increased expression of Vascular Endothelial Growth Factor (VEGF). Bevacizumab is a drug that neutralizes the biological activity of VEGF. The molecular structure of bevacizumab is a recombinant humanized antibody. Its use reduces vascularization in the foci of increased VEGF expression which slows down tumor growth and also helps restore vision in a number of ophthalmic diseases. To determine the concentration of bevacizumab in human biological fluids a test system based on Enzyme-linked Immunosorbent Assay (ELISA) is presented.Aim. Aim of this study is the validation of this test system.Materials and methods. Blank sera of volunteers, bevacizumab solution, enzyme-linked immunosorbent assay, solid-phase sandwich ELISA kit, microplate photometer.Results and discussion. The following characteristics of the test system were determined: the lower limit of quantification is 2.0 mcg/ml, the upper calibration range is up to 200 mcg/ml, the accuracy and precision within one series and between series does not exceed 20 %, and the total error of the method – 30 %, short-term stability for samples at room temperature – 6 hours, long-term stability – 14 days at –20 °C, the ability to freeze/thaw of samples is up to three times, the ability to determine samples with a concentration above the upper calibrator after diluting in 2 times.Conclusion. The results obtained fully comply with international acceptance criteria and allow the use of the ELISA test system manufactured by LLC "Probiotek" for use in the field of clinical laboratory diagnostics.

Introduction. Polyprenols are known as a class of natural long-chain isoprenoid alcohols, which are natural bioregulators that directly participate in the synthesis of cell membrane glycoproteins. Their hepatoprotective activity is proven, as well other types of their pharmacological effects are known, which is the reason of significant interest in these substances as a promising medicinal product. It is non-trivial task to determine the sum of polyprenols in extracts as include design and implementation of accurate reproducible analytical methods, which will subsequently be used in standardization.Aim. Development and validation of the chromatographic-mass spectrometric technique for polyprenols identification and their quantitative assessment.Materials and methods. Chromatographic separation of polyprenols was performed by using an HPLC Agilent 1260 Infinity II (Agilent Technologies, США); with the mixture of methanol, n-hexane, propanol-2, and aqueous ammonium acetate solution as eluent in gradient mode. An AB Sciex QTrap® 3200MD (AB Sciex Pte. Ltd., Singapore) triple quadrupole mass spectrometer was used as a detector, with the registration of polyprenols adducts.Results and discussion. The conditions for chromatographic separation and detection of polyprenols were identified. The developed technique was validated for the following characteristics: specificity, limit of detection, limit of quantification, linearity, accuracy, precision, range of application, and stability.Conclusion. It was determined the content of polyprenols in the substance recieved from Ginkgo biloba L. and Picea abies L. The developed technique can be used in the future to assess the content of polyprenols in drug products or pharmaceutical substances.

Introduction. Improving the efficacy of chemotherapy is a non-trivial task of modern oncology. Its successful solution requires knowledge in many fields, including physiology, pathology, clinical oncology, pharmacology and others. The search for small molecules that selectively kill tumor cells led to the accidental discovery of erastin.Text. Erastin is a unique molecule that has a quinazoline fragment in its structure. Not so long ago it became known that the antitumour effect of this compound is due to the induction of ferroptosis – an iron-dependent form of cell death caused by lipid peroxidation. Erastin is able to induce ferroptosis through various biochemical pathways, including blocking of cystine-glutamate transport channel of cell membrane and potential-dependent anion channel of mitochondria, as well as activation of p53 protein.Conclusion. Pharmacological induction of ferroptosis by erastin and its analogues represents a promising direction in cancer chemotherapy. In addition, erastin and its analogues are able to increase sensitivity to chemotherapy and radiation therapy, which allows us to talk about the possibility of their use in the combined treatment of malignant neoplasms.

Introduction. The secretome of mesenchymal stem cells (SMSC) is widely used in medicine. It is most often used due to its immune-modulating and regenerative properties in the treatment of autoimmune, immuno-mediated and other diseases due to its anti-inflammatory, neuroprotective and regenerating action. In many studies, exosomes isolated from SMSC are used as a therapeutic agent. In recent years, the interest in the development of products containing SMSC for external use has increased. Similar drugs are planned to be used in the treatment of diabetic wounds, for skin regeneration, the treatment of inflammatory diseases, as well as alopecia. There are multiple studies on increasing collagen secretion and reducing skin photosensitivity in preclinical studies, which confirms the significant potential for the use of SMSC in dermatology and cosmetology. The purpose of this review was to study the potential of using conditioned medium in medicines for external use, approaches to standardization of SMSC as a pharmaceutical substance and methods of increasing percutaneous delivery.Text. SMSC as an active pharmaceutical ingredient is a transparent liquid from yellow to orange in color with a characteristic odor. The pH of the ready-to-use SMSC composition ranges from 7.0 to 7.5, which allows it to be used in topical and external applications without the addition of stabilizers or pH correctors. Problems of delivery of SMSC through the epidermis are most often solved by placing the secretome in hydrogels, using exosomes or technology using microneedles. Since 2022, after legislative changes, measures have been taken to register and introduce into clinical practice domestic drugs based on cellular products. However, as the analysis showed, it will take some time before the appearance of original medicines based on SMSC, and today in the Russian Federation only products related to cosmetics and veterinary drugs, as well as zoocosmetics, are produced so far.Conclusion. SMSC may also prove to be a safer and more effective substance for the potential treatment of a wide range of acute and chronic diseases. But despite the large number of positive results of using SMSC for wound healing in animals, as well as clinical studies on skin regeneration, there are no studies of its safety and effectiveness, as well as standardization of the production process.

The paper presents well-known iconical, as well as new, recently discovered facts about the history of the creation and formation of the Apothecary prikaz as a structure of Russian state administration of medicine. This paper makes references to the scientists-historians of medicine who have made a special contribution to the study of the history of Russian pharmacy and the Apothecary prikaz. In particular the special role of V. Richter, N. E. Mamonov and N. Ya. Novombergsky in search, research, and preparing for publishing documents of the Apothecary prikaz is noted. Despite more than 200 years of studying of Apothecary prikaz’s documents, many disputes about the time of its setting up continue to the present day. The structure and functions of this organization in common structure of the Moscow state are still being discussed.

Introduction. The State Pharmacopoeia of the Russian Federation, XIV-th edition (SP XIV), includes 107 monographs devoted to medicinal plant materials. The purpose of the study was to identify incorrect Latin names of medicinal plants in the monographs of the XIV edition, study the officially accepted Latin names and taxonomic position of medicinal plants in accordance with the contemporary system of flowering plants, and justify the need to make changes in subsequent editions of the pharmacopoeia.Text. 44 cases of incorrect Latin names were found. This is explained by the fact that when developing new pharmacopoeia monographs, either Latin names historically established in Russian pharmacognosy were used, or names that were legal at the time of the last edition of the Pharmacopoeia. The bulk of nomenclatural changes are associated with the adoption of the new APG system of flowering plants, based on molecular genetic data. The paper contains lists of plants for which the State Pharmacopoeia XIV contains an incorrect name of the genus, species, family or author, indicating the correct name, as well as comments on the rules of modern botanical nomenclature.Conclusion. In connection with the prospects for processing monographs on medicinal plant raw materials for the State Pharmacopoeia XV-th edition, as well as the EAEU Pharmacopoeia, the harmonization of the nomenclature of pharmacopoeial plants with modern international requirements becomes especially relevant.

Introduction. Foeniculum vulgare Mill., commonly known as fennel or drugstore dill, is very common as one of the world's oldest spice plants, which has significant economic importance and wide application in the pharmaceutical industry. In medical practice, the fruits of this plant are mainly used, which are included in the State Pharmacopoeia of the XIV edition and are a source of essential oil. They are used as an antispasmodic and carminative agent in the form of an infusion. Fennel grass harvested before flowering is used for food, as well as fruits, stems and inflorescences of the plant as a seasoning.Text. The purpose of this study is to summarize scientific papers on the morphological characteristics, phytochemical compounds, therapeutic properties and basic mechanisms of pharmacological activity of F. vulgare. A systematic literature search was conducted using relevant keywords such as "fennel", "Foeniculum vulgare Mill.", "therapeutic" and "pharmacology" in well-known databases, including ScienceDirect, Scopus, EBSCO and Medline. The search covered articles published before April 25, 2023 in available journals. The results of the study showed that fennel has a wide range of pharmacological properties, including antioxidant, anti-cancer, anti-inflammatory, antifungal, antibacterial and estrogenic effects. These effects can be explained by the presence of aromatic compounds, in particular anethole, estragole and fenchone, which are abundantly present in fennel.Conclusion. The diverse pharmacological properties and rich chemical composition of fennel make it a promising raw material for the development of new medicines. Further study of the therapeutic potential of fennel through in vivo and in vitro studies will contribute to the establishment of mechanisms of pharmacological action of biologically active substances (BAS) of fennel.