Farmatsevtychnyi zhurnal

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ISSN / EISSN : 0367-3057 / 2617-9628
Total articles ≅ 231
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K. V. Semchenko,
Farmatsevtychnyi zhurnal pp 78-85; doi:10.32352/0367-3057.6.20.08

Abstract:
The existing range of medicines is represented by a variety of dosage forms. Among them a significant proportion takes oral solid dosage forms, in particular capsules. The introduction of active pharmaceutical ingredients in the capsule composition does not require the addition of flavouring agents and requires a significantly lower amount of excipients compared to the formation of tablet dosage forms. In the development of dosage forms based on extracts of medicinal plants, the rational choice of the dosage form is important. The use of capsules allows making a composition of several extracts, providing the proper consumer characteristics of the finished product. The aim of the workis to study methodological approaches to the development of the drug «Phytohelmin», proposed for use in the 3rd phase of the treatment of helminthiasis of the digestive system. As the objects of research scientific works of domestic and foreign authors, databases and own findingswere selected. When conducting the own research, we used methods of bibliosemantic analysis, systematization and generalization of data. Capsules are characterized as a dosage form: the definition, classification, features, advantages and disadvantages are presented. When developing a medicine for the treatment of helminthiases of the digestive system in phase III (eliminating the consequences of the disease and restoring the functions of the gastrointestinal tract), we selected the solid capsule dosage form. We present a decision tree for 6 stages of choosing the medicinal plant material to justify the capsule composition under the conditional name «Phytohelmin». 7 Degrees of the general algorithm for pharmaceutical development of capsules are described and solutions for each stage directly for the capsules of the proposed composition are given. Based on the results obtained, the main methodological approaches to the development of drugs in the form of capsules are formulated, in particular, capsule characteristics and classification are given, and the advantages and disadvantages of this dosage form are analyzed. The tree of decisions on the choice of medicinal plant materials in the development of medicines and the final composition of the capsules «Phytohelmin», obtained on the basis of its application, is given. The general algorithm for the pharmaceutical development of capsules and the corresponding solutions for the development of «Phytohelmin» capsules based on it in accordance with the requirements of Guide 42-3.1: 2004 «Quality Guide. Medications. Pharmaceutical Development» is described.
, E. V. Litvinova, A. G. Lisna
Farmatsevtychnyi zhurnal pp 3-15; doi:10.32352/0367-3057.6.20.01

Abstract:
The global economic crisis, which is linked to the coronavirus pandemic, has also affected pharmaceutical logistics. Therefore, the improvement of logistics processes within the pharmaceutical supply chain to increase the access to health care to the population in a pandemic becomes especially important. The aim of the work is to study and summarize the main problems of pharmaceutical logistics in a coronavirus pandemic and substantiate the reserves to improve the functioning of pharmaceutical supply chains. To achieve the goal of the study, an analysis of the domestic scientific literature and the current regulatory framework of Ukraine was conducted. It has used abstract-logical, monographic research methods and system analysis, as well as the method of expert survey. Realizing the importance of providing the population with necessary medicines during the pandemic in Ukraine on October 14, 2020, the Law «Changes to the article 19 of the Law of Ukraine "On Medicinal Products" on Electronic Retail Trade in Medicines» of September 17, 2020 № 904-IX has enforced. It has been evaluated the factors influencing the efficiency and coordination of the activities of pharmaceutical supply chain participants. A risk management algorithm for pharmaceutical supply chains has been developed, its structural elements and relationships have been identified. The presented algorithm will allow analyzing and estimating any deviations from the planned parameters in pharmaceutical supply chains on the basis of establishment of system of the corresponding indicators and on the basis of this information to define effective methods to counter the risks. The urgency of the problem of increasing the reliability and safety of domestic pharmaceutical supply chains in a pandemic has proved. It is justified that the introduction of digital technologies will increase the reliability, transparency and quality of business processes in the pharmaceutical supply chains during a pandemic, drastic changes in the pharmaceutical market and low predictability of demand for medicines and medical devices. The main problems of logistics in a pandemic in the domestic pharmaceutical industry are studied. It has established that the narrowest places in the organization of pharmaceutical supply chains are the improper organization of information exchange between pharmaceutical supply chain participants and the insufficient professional level of production interaction of managers. It has established the priority directions of increase of stability and reliability of functioning of pharmaceutical supply chains which is a necessary condition of accessibility of pharmaceutical provision of the population, especially in the conditions of a pandemic.
K. P. Schabelnyk, S. V. Kholodnyak, N. M. Polishchuk,
Farmatsevtychnyi zhurnal pp 65-77; doi:10.32352/0367-3057.6.20.07

Abstract:
In spite of the achievements in the chemistry of triazoloquinazolines, the synthetic possibilities of this class of compounds are not exhausted, some problems remain unresolved and require further study. 2-R-[1,2,4]triazolo[1,5-с]quinazolines are among them due to insufficiently explored but at the same time interesting in both chemical and biological aspects. Undoubtedly «pharmacophore» has the crucial role in the response of a biological action. It is contained in this heterocycle namely the substitute position 2. In view of the above, we attempted to modify triazolo[1,5-с]quinazoline by introducing a methyl group or halogens (fluorine, chlorine, bromine) into a benzene moiety and a triazole moiety of a cycloalkyl or heterocyclic substituent molecule. The aim of this work is to develop simple and affordable methods of the synthesis of new 2-cycloalkyl-(hetaryl-)-[1,2,4]triazolo[1,5-с]quinazolines, quinazolines, to study their physical and chemical properties and to conduct primary screening for antibacterial activity The antimicrobial activity of the synthesized chemical compounds was performed by the method of two-fold serial dilutions in Mueller–Hinton broth (for strains of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) and in Saburo broth (for Candida albicans ATCC 885–653). MIC (minimum inhibitory concentration), MBсC and MFсC (minimum bactericidal and fungicidal concentrations respectively) was determined. The optimal method of synthesis of 2-cycloalkyl-(hetaryl-)-[1,2,4]triazolo[1,5-с]quinazolines, which represent value as chemical reagents for further transformations and study of biological activity is substantiated and developed. The possibility of «one-pot» synthesis of the target compounds with 4-hydrazinoquinazolines and cycloalkylcarboxylic acids under conditions of activation of the carboxyl group N,N¢-carbonyldiimidazole is shown. Conducted microbiological screening of 2-cycloalkyl-(hetaryl-)-[1,2,4]triazolo[1,5-с]quinazolines revealed a number of promising compounds that inhibit the growth of St. aureus (МІС 25‒50 μg/ml) and C. albicans (25‒50 μg/ml). The optimal method of synthesis of 2-cycloalkyl-(hetaryl-)-[1,2,4]triazolo[1,5-с]quinazolin by cyclocondensation (3Н-quinazoline-4-ylidene)­hydrazides withcycloalkyl-(hetaryl)carboxylic acidsis substantiated and developed. The structure and individuality of the synthesized compounds were confirmed by elemental analysis, physicochemical methods (1H NMR-spectroscopy, HPLC/MS). The peculiarity of the 1H NMR spectra of this heterocycle is discussed, namely the significant paramagnetic shift of benzene protons and the characteristic weak-field single-proton singlet of the proton of position 5 of the heterocycle, which is a confirmation of recycling isomerization by Dimrot rearrangement. The structure-activity relationship is discussed and the study of the most active compounds for a wider range of strains and resistant strains of bacteria and fungi is recommended.
V. M. Kravchenko, Z. V. Shovkova, I. V. Senyuk
Farmatsevtychnyi zhurnal pp 86-91; doi:10.32352/0367-3057.6.20.09

Abstract:
Searchingof drugs that normalize the function of the digestive glands are important because disruption of digestion underlie the pathogenesis of many diseases such as gastroesophageal reflux disease, hepatitis, gastric ulcer, irritable bowel syndrome, cancer etc. The use of herbal objects containing fibres is a promising direction for solving of the mentioned problem. We were attracted by fruits of Prunus domestica which are rich in fibres (homo- and heteropolsaccharides) and are used in folk medicine as a laxative and hepatoprotective agent. The aim of this experimental study was to investigate the lipotropic properties of «Prunofit» extract. The study of lipotropic properties of the «Prunofit» was carried out in the conditions of subacute toxic liver damage caused by the introduction of ethanol.The content of total lipids (TL), total cholesterol (TCh), triacylglycerols (TGs), unsaturated fatty acids (UFA) and total phospholipids (TPL) were determined in liver and blood serum. Obtained results of the lipotropic properties study of the «Prunofit» extract at a dose of 200 mg/kg against the background of alcoholic liver damage showed a decrease in the intensity of lipolysis, fatty hepatosis, and manifestations of hyperlipidemia. It has occurred due to a decrease in the content of total lipids, cholesterol, triglycerides and free fatty acids in the homogenate rat liver by 27.9%, 7.2%, 27.5% and 38%, respectively, and rat serum by 28%, 42.2%, 8.15%, 47.1%, respectively, compared with the control pathology. Against the background of model pathology, «Prunofit» extract tended to increase the content of total phospholipids in the liver homogenate by 37.34% and in serum by 30.2% compared with the control pathology. According to its ability to inhibit fatty liver infiltration, the «Prunofit» extract was at the level of the reference drug «Methionine» at a dose of 155 mg/kg.
, O. M. Semenov, N. M. Maksymovych, M. V. Slabyy, B. M. Zalisky, I. H. Mudrak
Farmatsevtychnyi zhurnal pp 16-25; doi:10.32352/0367-3057.6.20.02

Abstract:
The pharmacist as a member of the medical team is responsible for the life and health of the population in the context of the COVID-19 pandemic in accordance with the recommendations of WHO and FIP, 2020. According to the WHO, 82% of patients with COVID-19 are treated by a family doctors and receive pharmaceutical care at the nearest pharmacies, but this can lead to unwanted contact between infected and healthy people, as well as contact with a pharmacist when dispensing drugs, which can lead to COVID-19 infection. Compliance with quarantine measures in accordance with the Resolutions of the Cabinet of Ministers and Orders of the Ministry of Health of Ukraine in pharmacies is an important component of overall safety during a pandemic, and the role of pharmacists in preventing the COVID-19 pandemic is important. The aim of this study was to conduct an expert evaluation of the effectiveness of quarantine measures due to the orders of the Ministry of Health of Ukraine in pharmacies. The sample of 586 experts included pharmacists, heads of pharmacies in 6 regions of Ukraine: Lviv, Vinnytsia, Ivano-Frankivsk, Zakarpattia, Khmelnytsky, Chernivtsi. According to a specially developed questionnaire «Assessment of the effectiveness of quarantine measures in the pharmacy at COVID-19» pharmacists were interviewed during March-October 2020. Methods of face-to-face questionnaires, interviews with the help of information and communication technologies, methods of generalization and systematization are used. According to the results of the analysis of 586 questionnaires, the respondents were ranked according to the parameters: specialty, work experience, qualification category. It was found that in 97.5% of pharmacies quarantine measures were implemented in March, in 2.5% pharmacies were in April 2020. The results of the pharmacists' survey show that the most effective quarantine measures are: wearing a protective mask (99.0%), washing hands and using disinfectants (97.0%), maintaining a social distance between visitors and pharmacy staff, as well as visitors to each other 1.5 m (94.5%), washingof pharmacy surfaces and floors with disinfectant solutions (91.0%), ventilation of pharmacy rooms (89.5%). Systematization of these questionnaires showed that 100% of pharmacists consider it necessary and prospective the approval by Ministry of Health of Ukraine a separate «Protocol of the pharmacist for the release of medicines and medical devices for the treatment of uncomplicated forms of coronavirus infection COVID-19» to optimize pharmaceutical care. Pharmacist as member of the medical team during the COVID-19 pandemic should conduct educational work among the population to prevent the spread of the COVID-19 pandemic.
Farmatsevtychnyi zhurnal pp 46-55; doi:10.32352/0367-3057.6.20.05

Abstract:
The conditions of modern pharmaceutical market development require leadership at each level that lets not only respond rapidly and efficiently on the changes of the environment but initiate the necessary changes. Leaders as agents of changes can transform people’s values, to motivate and inspire, to form the vision of development of healthcare system and pharmaceutical sector taking into account the principles of system thinking for the provision of population with available, quality and safe pharmaceutical care and the improvement of their life. The aim of the work is the development of an elective discipline «Leadership in Pharmacy» for training Master of Pharmacy, Industrial Pharmacy. The literature review based on the data of international and foreign educational standards of higher pharmaceutical education, the current national educational standard, the experience of teaching subjects devoting to leadership in pharmacy both abroad and in Ukraine has been carried out. Such a scientific quantitative method as a survey has been used. 221 students from the School of Pharmacy at Bogomolets National Medical University have taken part in the survey. The recommendations of the International Pharmaceutical Federation pay attention to the advisability of forming leadership competencies for pharmaceutical workers. The national standards of higher pharmaceutical education in the USA, Great Britain, Australia, Canada include a specific list of leadership competencies. The domestic standard of higher education for getting a Master’s degree in Pharmacy, Industrial Pharmacy includes certain general competencies based on the leadership. Some leadership skills are listed as special competencies and they are reflected in the discipline «Pharmaceutical Management and Marketing». However, a discipline aimed at the complex and systematic formation of leadership competencies is not presented in the working educational plan for training Masters in the field of knowledge «Healthcare» and specialty «Pharmacy». About 70% of the School of Pharmacy students at Bogomolets National Medical University think that the materials devoted to leadership «worth including» to the educational program and 28% of them notice that «rather worth including». According to the students’ opinions, the most interesting leadership topics are traits of leaders aimed at the success, leadership and team, the formation of leadership strategy – 76%, 72% і 70% respectively. The structure of the elective discipline «Leadership in Pharmacy» with an indication of the aim, list of topics, and the desired educational outcomes (competencies) has been presented. The elective discipline «Leadership in Pharmacy» considering the formation of leadership skills at three successive levels, namely individual, team and organization has been developed. This discipline consists of the following modules: «Foundations of Leadership. Personal Leadership», «Leadership and Collaboration», «Leadership and Organizational Change».
E. O. Karpun, V. V. Parchenko
Farmatsevtychnyi zhurnal pp 56-64; doi:10.32352/0367-3057.6.20.06

Abstract:
Hypoxia is a discrepancy between the required energy of the cell in the mitochondrial oxidative phosphorylation system. The immediate cause of the deficiency is a decrease in the oxygen concentration in the mitochondria. Today there is a huge demand for the development of new anti-hypoxic drugs. t is known that 1,2,4-triazole compounds can have antimicrobial, anti-inflammatory, anti-hypoxic effects. Modification of the 1,2,4-triazole nucleus is a productive way to create original active molecules with a non-planar structure, for their binding to bio-target substrates. Derivatives of bis-1,2,4-triazoles may become potential compounds with anti-hypoxic action. The aim of our work was to synthesize new S-derivatives of 4-alkyl-5-(((3-(pyridine-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols, to investigate their physicochemical parameters using modern complex physicochemical research methods and to conduct primary pharmacological screening for anti-hypoxic activity in models of acute hypoxia with hypertension. The object of the study was the S-derivatives of 4-alkyl-5-(((3-(pyridine-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols. The structure of the synthesized compounds was confirmed by elemental analysis (CHNS), 1H NMR, the individuality of the molecules was proved by chromatographic mass spectral analysis. 1H NMR signals for substances are consistent with the proposed structure. The study of the anti-hypoxic activity of the got compounds of the series of S-substituted bis-1,2,4-triazoles was carried out on models of acute hypoxia with hypertension, where Mexidol (5%) 200 mg/kg as a reference drug. New S-derivatives of 4-methyl-5-(((3-(pyridine-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols (I a) and 4-ethyl-5-(((3-(pyridine-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols (I b) with acyl-aryl, acyl-alkyl and alkyl substituents. We studied their spectral parameters, physicochemical properties in the conditions of GC/MS, elemental analysis, 1H NMR spectroscopy. According to the results of biological studies on the anti-hypoxic effect, it was found that 1-((4-ethyl-5-(((3-(pyridine-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)propane-2-one is a compound that exceeds the anti-hypoxic activity of Mexidol and increases the lifespan of rats by 1.0% relative to the reference drug.
N. L. Khanyk, , G. I. Bilushchak, T. Ya. Khanyk
Farmatsevtychnyi zhurnal pp 37-45; doi:10.32352/0367-3057.6.20.04

Abstract:
Rheumatoid arthritis (RA) is an unpredictable and progressive inflammatory disease of the joints of an immune nature, which in general for various reasons reduces the life expectancy of patients by 5 to 10 years. Pharmacotherapy of RA is based on long-term use of a large number of drugs of different pharmacotherapeutic groups, the cost of which varies significantly. The above makes the study of economic parameters of RA treatment an urgent problem. The aim of the study was to analyse the cost characteristics of pharmacotherapy of inpatients with RA in a hospital in order to optimize the cost of medication for these patients. The data of medical cards and medical records of 89 and 108 inpatients with RA, which were treated in the rheumatology department of the 4th Lviv City Clinical Hospital in 2009 and 2019, respectively, were selected as objects of the study. The methods of information retrieval, mathematical statistics, frequency, comparative, content analysis, data generalization, cost analysis were used. Disease-modifying antirheumatic drugs (DMARDs), glucocorticosteroids (GCs), and nonsteroidal anti-inflammatory drugs (NSAIDs) were grouped into six schemes for the RA pharmacotherapy in 2009 and 2019. An increase in the number of appointments of those schemes in which DMARDs were used has been established. The maximum share in both analysed periods was occupied by the triple pharmacotherapy scheme, which included all the above-mentioned drugs. This scheme was also the most expensive and its value at average retail prices (ARP) increased the most (9.4 times) from 2009 till 2019. During the analysed period, the average salary in Lviv region increased in 5.4 times, while the cost change indices (Ic) of different pharmacotherapy schemes, calculated on the basis of ARP, ranged from 6.9 for the two-component scheme with DMARDs and NSAIDs to 9.4 for the three-component scheme with DMARDs, GCs and NSAIDs. The analysis of affordability indices (Ia) showed that the most accessible was a two-component scheme, which included DMARDs and NSAIDs (Ia = 0.78). The study of the influence of the cost of the treatment schemes on the frequency of their prescribing using correlation analysis showed a very high dependence of these indices (R = 0.97). Pairwise correlations of pharmacotherapy appointment change indices (Iap) from Ic based on minimum (RPmin), maximum (RPmax) or average retail prices in Lviv pharmacies made it possible to establish a very high pair dependence of Iap from Ic calculated only on the basis of RPmax or ARP (R = 0.90). Thus, the analysis of patients' consumption of drugs for pharmacotherapy RA in the hospital allowed us to establish that in 2019 the treatment of RA became less available in comparison to 2009.
I. Yu. Revyatskyy, A. I. Boiko
Farmatsevtychnyi zhurnal pp 26-36; doi:10.32352/0367-3057.6.20.03

Abstract:
In modern conditions of reforming the Ukrainian Health Care system based on the introduction of innovative digital information technologies, the development of a methodology for the computerization of pharmaceutical information exchange processes is relevant. The purpose of our study was to develop a methodology for creating a unified accounting system (UAS) of information on pharmaceutical and medical products (Ph&MP) in Ukraine (taking into account the current standards of computer systems for structuring and fixing information, as well as in accordance with international standards for automated identification of information about Ph&MP. The objects of the research were: scientific and specialized publications devoted to the issue of the implementation of a system of accounting and tracking of medical and health care in the EU, USA, Canada;pharmaceutical information with tracking and recording the established information flows in computer databases.The main research is based on the methodology of pharmaceutical informatics: creation of pharmaceutical computer databases, coding of pharmaceutical products. The method of system analysis processed publications on the types of Ph&MP encodings in the EU, USA, Canada. In the scientific work, the international standards for the sale of information in two-dimensional shaded codes of the DataMatrixECC 200 standard are highlighted, which is one of the information blocks on the basis of which the development of the UAS Ph&MP database structure should be based.The structure and interconnection of information blocks for the accounting of Ph&MP units using GTIN and serial numbers in the database of structural units of business entities of the pharmaceutical market of Ukraine have been developed. A systematic analysis of the types of Ph&MP encodings in the EU countries, the USA, and Canada has been carried out.Highlighted rational approaches to the formation of coding and accounting for Ph & MP, taking into account national characteristics. The basis of the integral structure of the UAS Ph&MP with basic information blocks has been developed.Approaches and principles to the methodology of its formation are given, taking into account the current standards of computer systems for the structuring and fixing of information, as well as in accordance with international standards for automated identification of information about Ph&MP. The requirements for the compliance of computer databases of structural units of business entities with modern standards for preserving pharmaceutical information necessary about medicines when accounting are presented.
Farmatsevtychnyi zhurnal pp 68-81; doi:10.32352/0367-3057.5.20.08

Abstract:
The tincture is a traditional liquid dosage form for the pharmaceutical market of Ukraine. Today, the range of the tinctures of Ukrainian manufacturers has 21 different items, while only six monographs on different tinctures are included in the State Pharmacopoeia of Ukraine. For standardization of tinctures, different combinations of specific and non-specific physical and chemical methods are used. The high-performance thin-layer chromatography (HPTLC) is a modern and specific chromatographic method, that can be used for the identification of polyphenolic substances responsible for a wide range of pharmacological activities of the tinctures. The purpose of the study was to identify and compare chromatographic fingerprints (images of chromatograms and peak profiles from images) of flavonoids and phenylpropanoids of 10 tinctures of Ukrainian production in the harmonized mobile phases, to select for each tincture the specific marker zones, to determine the suitability of the specified chromatographic conditions for standardization of the tincture and the possibility to perform in these conditions the quality control for several different tinctures in-parallel. The objects of the investigation were Hawthorn tincture, Peppermint tincture, Sage tincture, Motherwort tincture, Calendula tincture, Sophora tincture, Echinacea purpurea tincture, Valerian tincture, Peony tincture, Eucalyptus tincture. The research was carried out using the HPTLC method in the HPTLC automatic herbal system (CAMAG, Switzerland) on the base of two laboratories. For each investigated tincture, the determination and comparison of HPTLC chromatographic fingerprints (images and peak profiles of images) of flavonoids and phenylpropanoids obtained in different harmonized mobile phases were performed. In the harmonized chromatographic conditions the difference in separation of the bioactive substances was determined; the characteristic marker substances of the tinctures were identified; the suitability of the mobile phase for individual analysis of the tincture or in-parallel analysis of different tinctures on the same plate were determined; the possibility to replace one mobile phase by another, if needed, was determined. Proposed HPTLC methods were developed using modern procedure and approach. These allow to reduce of the scope and time of analysis, optimize the economical and labor costs. The findings are of special importance for the pharmaceutical manufacturers and quality control laboratories that perform analysis on a large scale.
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