bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Colloidal Structure and Biopharmaceutical Properties of New Antibacterial Composition of Gramicidin S
Authors: Drannikov A. A. , Vatlin I. S. , Trusova M. Е. , Di Martino A. , Krivoshchekov S. V. , Guriev А. M. , Belousov M. V. 
Published: November 2021

Introduction. Gramicidin S has been conventionally manufactured as buccal tablets. However, in the past decade, the interest in the development of spray formulations has been growing. Those formulations contain excipients that enhance the solubility of the antibiotic in water solutions. However, the real structure of gramicidin S containing sprays remains unrevealed.Aim. Investigation of colloidal structure and biopharmaceutical properties of new gramicidin S antibacterial composition.Materials and methods. The composition sample was obtained using gramicidin S dihydrochloride, propylene glycol, polysorbate-80, ethanol and purified water. Raman spectroscopy has been performed to determine the composition of the phases. Dynamic light scattering analysis was performed to characterize the composition particles. Release of gramicidin S was performed by dialysis method and the concentration was determined by HPLC. The antimicrobial properties were investigated in accordance with the requirements of the XIV edition of the Russian pharmacopoeia.Results and discussion. Dynamic light scattering analysis results show gramicidin S formulation particles having an average size in solution 5–50 nm and ζ-potential (–1.1: +7.9 mV). Based on the obtained data on the composition properties and formulation parameters it was classified as colloidal solution. The kinetic stability evaluation was performed. We compared the solubility in water and release parameters of the active pharmaceutical ingredient in the native state and in the micelles. The enhancement of the antimicrobial activity of the peptide in the colloidal solution was confirmed and ascribed to the synergic effect gramicidin S – surfactant.Conclusion. We reported the colloidal type of the composition, that aggregate gramicidin S at a concentration of 8 mg/mL. We found that gramicidin S inclusion into the colloidal solution led to significant efficiency increase, which reveals the potential to reduce the drug dose and side effects level.
Quantitative Anatomical Characteristics of the Leaf Blades of the Several Species of <i>Crataegus</i> L.
Authors: Sagaradze V. A. , Babaeva E. Yu. , Kalenikova E. I. , Trusov N. A. , Peshchanskaya E. V. 
Published: November 2021

Introduction. The Crataegus L. (Hawthorn) is a common herb in numerous Pharmacopoeias. The State Pharmacopoeia of the Russian Federation provides hawthorn fruits and flowers for medical utilization. With that, the literature data confirms the medical utility of hawthorn leaves since the “leaves” and the “flowers with leaves” have pharmacopoeial status worldwide. Therefore, those are considered as prospective forms of Crataegus raw material for Russian pharmaceutical production. However, most species remain poorly pharmacognostically investigated regarding the quantitative microscopic characteristics (the sizes of stomatal apparatus (SA) and epidermal leaf blade (LB) trichomes), which could be substantial for establishing the authenticity of the raw material.Aim.Examine epidermal anatomy of Crataegus spp. Leaf blades (LBs) and perform a comparative study of several quantitative diagnostic features of LBs of hawthorn plants from the sect. Sanguineae and the sect. Crataegus, growing in diverse regions of the Russian Federation.Materials and methods. Samples of hawthorn leaves (C. sanguinea, C. maximowiczii, C. dahurica, C. rhipidophylla, C. monogyna and C. pallasii) were collected in natural habitats in Western Siberia (Kemerovo) and in arboretums of Botanical Gardens (Moscow, Stavropol). Measurements of anatomical structures were carried out using a light microscope accompanied by an ocular micrometre.Results and discussion.The LB surface phenotypic diversity within hawthorn species and sections was studied. The LBs were described in terms of meterages (longitude and width) of SA, meterages and shape of sedentary multicellular leaf teeth glands. The peculiarities of pubescence and the sizes of simple unicellular non-glandular trichomes were also observed.Conclusion. The results of quantitative anatomical examination provided the characteristic features determining these elements at the species and section levels. Thus, it may facilitate authentication and quality control of whole or ground Crataegus medicinal raw material.
Simultaneous Determination of Candesartan and Hydrochlorothiazide in Human Plasma by HPLC-MS/MS
Authors: Karnakova P. K. , Komarov T. N. , Archakova O. A. , Shchelgacheva D. S. , Aleshina A. A. , Bagaeva N. S. , Karpova P. A. , Shohin I. E. 
Published: November 2021

Introduction. Combined drugs have the greatest efficacy and safety in arterial hypertension treatment. The combination of candesartan and hydrochlorothiazide (AT1-receptor antagonist and a thiazide diuretic, respectively) provides high efficiency of antihypertensive combination therapy, therefore it is widely used in medical practice. Developing a method for simultaneous determination of candesartan and hydrochlorithiazide in human blood plasma is necessary for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs.Aim. The aim of this study is to develop a method for quantitative determination of candesartan and hydrochlorothiazide in human plasma by high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) for further bioequivalence studies.Materials and methods. Determination of candesartan and hydrochlorothiazide in human plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation. Internal standard: mixed solution of valsartan and indapamide. Mobile phase: 0.1 % formic acid solution in water (eluent A), 0.1 % formic acid in acetonitrile (eluent B). Column: Phenomenex Luna Phenyl-Hexyl, 50x4.6 mm, 5 μm. Analytical range: 2.00– 300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. Ionization source: electrospray ionization. Detection conditions: 441.10 → 192.00 m/z, 441.10 → 263.15 m/z (candesartan), 295.85 → 269.00 m/z (hydrochlorothiazide), 436.00 → 207.05 m/z (valsartan), 363.85 → 132.10, 363.85 → 189.00 m/z (indapamide).Results and discussion. This method was validated by selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. The developed method meets the requirements for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union.Conclusion. The analytical range was 2.00–300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. The method was applied in BE study of the combination of candesartan and hydrochlorothiazide.
The Use of Digital Technologies for the Purpose of Improving Methodological Approaches to the Creation of a Pharmaceutical Quality System at Enterprises for the Production of Medicines
Authors: Goryachkin V. V. , Smirnov V. А. , Shestakov V. N. , Abramovich R. A. 
Published: November 2021

Introduction. The article is devoted to the aspects of improving methodological approaches to the creation of a pharmaceutical quality system (PQS) at enterprises for the production of medicines, taking into account the possibility of using tools and means of digitalization. The relevance of the study is associated with the enduring importance of comprehensive high quality assurance in the development, production and release of medicines into circulation. The implementation of PQS requires numerous transformations of management and production processes, which can be facilitated by tools and elements of digitalization.Aim. To consider the potential and specific areas of application of digital technologies to improve the methodology and practice of developing and implementing PQS.Materials and methods. The state in the subject area was assessed on the basis of the results of economic and statistical analysis and forecasting of the implementation of PQS at Russian pharmaceutical enterprises that have positive and comparatively long experience in this area: the companies LLC "OZON" and JSC "AKRIKHIN". The assessment was carried out by calculating the integral indicator of the effectiveness of the functioning of PQS, which is a set of weighted key performance indicators (KPI) for quality.Results and discussion. The importance of the introduction of PQS for the development of pharmaceutical enterprises and the presence of numerous difficulties in the implementation of PQS, which necessitates the improvement of methodological approaches in the subject area, are stated. It has been proven that even at those enterprises where PQS has been introduced with varying degrees of success, the use of digitalization tools would contribute to a faster, more systematic and high-quality implementation of PQS. Among the key areas of application of digital tools, the authors propose monitoring of quality indicators (using neural network cards) and the use of blockchain platforms and smart contracts to register the release of drugs of appropriate quality.Conclusion. Digital tools contribute to complex improvement in many areas of socio-economic activity. Their active use at pharmaceutical enterprises is intended to contribute to ensuring the proper implementation and uninterrupted functioning of pharmaceutical quality systems, through constant monitoring of the quality of manufactured products and registration of manufactured batches in high-precision information storage systems.
Alternative Methods for Dissolution Profile Comparison in the Dissolution Test
Authors: Romodanovsky D. P. , Goryachev D. V. 
Published: November 2021

Introduction. The article discusses the problem of assessing the similarity of the dissolution profiles of two batches of the nebivolol. The use of a generally accepted similarity factor for assessing equivalence is unacceptable in some cases, for example, for drugs with a high variability in the values of the release of the active substance from the formulation. At the same time, at present, there are no generally accepted approaches to comparing the profiles of the dissolution kinetics of drugs, with the exception of the method for assessing the comparability of profiles based on the mathematical calculation of the similarity factor f2, which has certain criteria that limit its application.Aim. To demonstrate alternative methods for assessing the similarity between the dissolution profiles of two drugs using a practical example.Materials and methods. The results of the comparative dissolution test of two series of nebivolol at a dosage of 5 mg. Five model-independent methods for assessing the equivalence of drug dissolution were used. Statistical data processing was performed using Microsoft Excel software.Results and discussion. The paper presents a practical example of using five alternative model-independent methods for assessing the equivalence of the dissolution profile. An example is used to illustrate the proposed equivalence limits and statistical methodology. Also, various approaches to determining the boundaries of equivalence have been proposed to assess the similarity of the dissolution profiles of an active substance.Conclusion. According to the results of the comparative dissolution test of two batches of nebivolol, it was shown that the use of the similarity factor as a criterion for assessing dissolution profiles led to a false positive result. In such cases, the possibility of using alternative methods for assessing the equivalence of dissolution profiles described in the article, or other methods presented in the scientific literature, should be considered, with a justification of their acceptability in each specific case.
Study of the physicochemical properties of the etravirine substance
Authors: Zolotov S. A. , Ponomarev E. S. , Dain I. A. , Demina N. B. , Zolotova A. S. 
Published: November 2021

Introduction. Etravirine, being one of the most popular antiretroviral drugs, doesn't have its physicochemical properties sufficiently described in scientific publications. Detailed information on the substance properties is necessary both for organizing the synthesis and for justifying the dosage form and technology for its production, as well as for identifying bottlenecks and critical parameters that affect the quality of the finished product.Aim. Study the etravirine physicochemical properties to model the design of studies to create an innovative dosage formMaterials and methods. Etravirine (MSN Life Sciences Pvt. Ltd., Hetero Labs Ltd.). The melting point was determined by the capillary method. Etravirine samples were studied via differential scanning calorimetry (DSC), X-ray powder diffractometry, IR and NMR spectroscopy. Particle size was determined using laser diffraction analysis. The shape and size of the crystals were determined with the help of transmission electron microscopy (TEM). The concentration of etravirine in aqueous media was determined using the HPLC method with a fluorescence detector. The concentration of etravirine in organic solvents was determined spectrophotometrically.Results and discussion. The X-ray powder diffractometry and IR spectroscopy helped to determine the fact that the studied substances represent the same polymorphic modification. The melting point of etravirine ranges from 259 to 263 °C. Melting is accompanied by decomposition. The substance is practically insoluble in aqueous media at pH values in the range from 1.2 to 6.8, soluble in some organic solvents, readily soluble in dimethyl sulfoxide, tetrahydrofuran, dimethylformamide, dimethylacetamide. The distribution coefficient in the "1-octanol/phosphate buffer solution pH 6.8" solvent system was 5.22. The experiment showed that the etravirine substance is lipophilic. Etravirine is found to be a highly crystalline substance and represents needle-shape prismatic crystals.Conclusion. Etravirine is a lipophilic substance, practically insoluble in aqueous solutions, soluble in a number of organic solvents. The studied substances turned out to be the same polymorphic modification. Since the melting of the substance is accompanied by decomposition, high temperatures processes should be avoided.Conflict of interest. The authors declare that they have no obvious and potential conflicts of interest related to the publication of this article.
Phenolic Compounds and Hepatoprotective Activity of Chicory Herb Extract
Authors: Saybel O. L. , Radimich A. I. , Dargaeva T. D. , Lupanova I. A. , Ferubko E. V. , Kurmanova E. N. , Martynchik I. A. 
Published: November 2021

Introduction. Chicory (Cichorium intybus L.) is widely applied for liver disease treatment by traditional medicine of different countries; as well, it is the object for pharmacological research of hepatoprotective activity. In this regard, the method for obtaining dry extract of wild chicory herb (WCHE) is developed in the All-Russian Research Institute of Medicinal and Aromatic Plants.Aim. Aim of the research is determination of the qualitative composition of phenolic compounds, identification of the substances prevailing in WCHE and conducting pharmacological screening of the extract.Materials and methods. WCHE chemical composition has been explored with HPLC-MS/MS method; the main components were determined quantitatively with HPLC-UF method using single compounds that were isolated by us earlier and identified by NMR spectroscopy. WCHE pharmacological screening of hepatoprotective activity research was involving 50 male rats. Acute toxic hepatitis in animals was induced by a single subcutaneous injection of 50 % oily solution of tetrachloromethane (TCM) at a dosage of 0.4 ml per 100 g body weight. One hour before administration TCM, animals received WCHE at the doses of 100 or 500 mg/kg. 48 hours after TCM administration, the activity of serum enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as the content of total bilirubin were determined for preliminary establishment of pharmacological activity. Pathomorphological studies of rat liver were carried out using histological methods. The liver histological structure was inspected using liver sections stained with hematoxylin and eosin.Results and discussion. The component composition of WCHE is represented by oxycoumarins, hydroxycinnamic acids and flavonoids. The dominant phenolic compounds are esculetin, chicoriin, chicoric, chlorogenic and caftaric acids. It was found under acute experimental toxic hepatitis, that preliminary WCHE administration reduces the toxic TCM effect on liver cells. In animals treated with WCHE at doses both 100 mg/kg and 500 mg/kg body weight, it was observed decreases in ALT activity by 35 % and 45 %, AST by 15 % and 28 %, alkaline phosphatase by 15 % and 21 %; the content of total bilirubin by 20 % and 29 %, respectively, in comparison with similar indicators in the group of animals that were not treated with the extract. The histological study showed that WCHE administration to animals at the doses of 100 and 500 mg/kg reduces dystrophic changes in hepatocytes, this effect is more pronounced at the extract dosage of 500 mg/kg.Conclusion. Main WCHE components are oxycoumarins (esculetin, chicoriin), hydroxycinnamic acids (chicoric, chlorogenic and caftaric). According to the results of screening studies, it was established that WCHE in doses of 100 mg/kg and 500 mg/kg is a promising object for further pharmacological research.
Antioxidant Activity of Silver-containing Bionanocompositions Based on Humic Substances in Cell Culture
Authors: Buyko E. E. , Zykova M. V. , Ivanov V. V. , Bratishko K. A. , Ufandeev A. A. , Grigorieva I. O. , Tsupko A. V. , Mikhalyov D. A. , Perminova I. V. , Belousov M. V. 
Published: November 2021

Introduction. Silver nanoparticles are promising agents for suppressing resistant strains of microorganisms and accelerating the purulent wounds healing. Oxidative stress disrupts normal wound healing processes, which leads to the formation of chronic non-healing wounds. Therefore, the determination of the ability of new wound healing agents to decrease the production of reactive oxygen species is a relevant task.Aim. The aim of the current study was to investigate the effect of silver-containing bionanocompositions based on humic substances on the basal and tert-butyl hydroperoxide-stimulated production of reactive oxygen species at the normal fibroblasts 3T3-L1 cell culture in vitro.Materials and methods. The study was carried out on 7 samples of initial humic substances and biomaterials with silver nanoparticles synthesized in the Laboratory of Natural Humic Systems, Faculty of Chemistry, Moscow State University named after M. V. Lomonosov. The intracellular production of reactive oxygen species was assessed using a 2,7-dichlorodihydrofluorescein diacetate fluorescent probe. Cells were cultured with samples for 24 h; tret-butyl hydroperoxide was used to stimulate the production of reactive oxygen species. Detection was performed fluorometrically using a microplate reader.Results and discussion. The most pronounced antioxidant activity was demonstrated by three samples of biomaterials with silver nanoparticles ultradispersed in humic substances matrices (CHS-AgNPs, CHP-AgNPs and CHE-AgNPs), which allows us to consider them as the most promising pharmaceutical agents for the treatment of purulent-inflammatory processes. The most probable mechanism of the high antioxidant activity of the studied biomaterials in relation to intracellular reactive oxygen species is the intrinsic activity of humic substances to bind reactive oxygen species, while silver nanoparticles in biomaterials catalyze the reduction processes of their interaction with reactive oxygen species.Conclusion. For the studied samples of biomaterials with silver nanoparticles ultradispersed in matrices of humic substances pronounced antioxidant activity was shown. Together with antibacterial properties, it makes it possible to consider them as potential agents for purulent wounds healing accelerating.
<i>In situ</i> Intranasal Delivery Systems: Application Prospects and Main Pharmaceutical Aspects of Development (Review)
Authors: Bakhrushina E. O. , Demina N. B. , Shumkova M. M. , Rodyuk P. S. , Shulikina D. S. , Krasnyuk I. I. 
Published: November 2021

Introduction. Intranasal delivery of in situ gel-forming systems is a complex but promising direction. Due to the high cost of developing a new chemical object or genetically engineered modification of biological molecules, pharmaceutical companies are focusing on developing technologies for new delivery systems for existing active pharmaceutical ingredients to improve their effectiveness and bioavailability. In situ systems for intranasal delivery, due to increased viscosity and mucoadhesion to the nasal mucosa, allow overcoming mucociliary clearance and ensuring complete absorption and prolonged release of drugs.Text. The article discusses the main advantages of intranasal in situ delivery systems shown in preclinical studies, as well as approaches to the technology of obtaining and standardization of these systems. The results of scientific research in this field over the past 15 years are summarized, the most promising polymers for creating thermoreversible and pH-sensitive compositions are identified, and modern methods for evaluating the sol-gel transition in situ are analyzed.Conclusion. The use of in situ systems for intranasal administration allows providing a high targeting of the delivery of synthetic and biological molecules to the brain. Currently, numerous pharmacokinetic and pharmacodynamic preclinical studies confirm the effectiveness of such systems, as well as their safety. Thermoreversible commercially available and directionally synthesized polymers (poloxamer 407, PLGA, NIPAAm, etc.), as well as chitosan, remain the most popular for the design of in situ delivery systems. In vitro and ex vivo methods with mucosa and artificial nasal fluid are widely used to assess the parameters of in situ gelation, but to increase the reproducibility of the methods and improve the correlation in vitro/in vivo, it is recommended to conduct modeling of the nasal cavity. Developing the technology and methods of screening of intranasal reversible systems will help to get closer to clinical trials and the entry of these delivery systems into the global pharmaceutical market.