State Pharmacopoeia Of Ukraine Research Articles

The study on the development of the composition of chewable lozenges with probiotic properties. 1. Substantiation of the active substance

In recent times, a new understanding of the concept of probiotics has emerged – the use of their metabolites instead of living cells of microorganisms. They can both inhibit the development of pathogenic bacteria and effectively stimulate the reproduction of indigenous microflora. It is possible that metabiotics will be more effective than traditional live probiotics. Taking into account the prospects of new-generation probiotic drugs and the rapid growth of interest of pharmaceutical market entities in such a new dosage form as lozenges, we have proposed to create chewable lozenges containing Lactobacillus exometabolites, which pharmacological action is aimed at preventing and treating an imbalance of the oral cavity microflora.Aim. To theoretically and experimentally substantiate the choice of the exometabolite complex of lactobacilli as the active substance of a medicinal product with probiotic properties in the form of chewable lozenges.Materials and methods. The exometabolite complex of the Lactobacillus plantarum UCM-2693 strain was used as the study object. Acidity, the lactic acid content, the optical density of a microbial suspension, as well as the quantitative count of lactobacilli were determined in accordance with the generally accepted methods specified in the State Pharmacopoeia of Ukraine (SPhU).Results and discussion. The bacteriotropic effect of the exometabolite complex of L. plantarum UCM-2693 was detected on lactobacilli of the probiotic drug “Lactobacterin-Biopharma” when cultured on a medium with exometabolites compared to the control sample. This technique has a stimulating effect on the acid formation, proliferation of probiotic microorganisms, changes the characteristics of their growth phases, namely reduces the lag phase, accelerates the exponential phase, which can accelerate the onset of the therapeutic effect, and is the proof of the feasibility of using this active substance in the composition of chewable lozenges with probiotic properties.Conclusions. The choice of the exometabolite complex of lactobacilli as the active substance of a new drug from the group of metabiotics in the form of chewable lozenges has been substantiated. The exometabolite complex of lactobacilli has been obtained, and its bacteriotropic effect has been studied.

The study of the diuretic activity and pharmacotechnological properties of a dry extract of Salvia sclarea L. growing in Tajikistan

Aim. To study the pharmacological activity of a dry extract of clary sage (DECS) growing in Tajikistan and its pharmacotechnological properties as basic stages in the development of the composition and technology of hard gelatin capsules with its content. Materials and methods. For the studies, we used DECS standardized by the content of the total amount of flavonoids and hydroxycinnamic acids. The quantitative content of the total amount of flavonoids was not less than 13.0 % calculated with reference to apigenin, and the quantitative content of the total amount of hydroxycinnamic acids was not less than 1.2 % calculated with reference to rosmarinic acid. The pharmacotechnological properties of DECS were studied according to methods of the State Pharmacopoeia of Ukraine (SPhU). Results and discussion. During screening, all doses of DECS studied showed a moderate diuretic activity. Thus, when using DECS in the dose of 100 mg/kg, the relative volume of the urine excreted by rats for 5 hours increased by 1.9 times, in the dose of 200 mg/kg – by 2.0 times, in the dose of 300 mg/kg – by 1.8 times compared to the same indicator in the negative control group (p˂0.05). When studying the complex of pharmacotechnological properties, it was found that DECS was a finely dispersed amorphous powder with particles of isodiametric form. DECS had an average bulk weight of 0.515 ± 0.002 g/mL, and the fluidity assessment showed that DECS had a very poor flowability, which value in the vibration mode of the device was 2.8 ± 0.1 g/s. According to the study of the fractional composition, DECS had a clearly expressed fine fraction with a particle size of less than 0.25-0.09 mm 84.68 %. Conclusions. Taking into account the results of the study of the diuretic activity and scientific literature data on the spectrum of the pharmacological activity of Salvia sclarea L, it is rational to consider DECS as a potential combined agent for enhancing the diuretic effect or in diseases of the urinary system accompanied by edema and inflammatory processes. The study of the pharmacotechnological indicators of DECS allows predicting the need to use certain groups of excipients to develop the composition and technology of capsules with its content, namely antifriction substances to improve fluidity and disintegrants to improve capsule disintegration, as well as substances that contribute to the compaction of bulk mass and moisture-regulating agents.

Application of the variability budget approach to the Dissolution test

The aim. This study aimed to evaluate the completeness of our knowledge about the sources of variation in the Dissolution test with 100 % release by compiling a variability budget.
 Materials and methods. The study was performed on 500 mg metformin tablets, using pharmacopoeial quality reagents, State Pharmacopoeia of Ukraine (SPhU) Metformin HCl reference standard, Pharmatest DT70 Dissolution apparatus, Perkin Elmer Lambda 35 spectrophotometer, Mettler Toledo XP 204 analytical balance, and ISO class A volumetric glassware. The SPhU metrological approach was employed.
 Results and discussion. The variability budget was compiled based on the comparison of uncertainty estimates obtained from the requirements for maximum permissible variation in normal analytical practice (UNAP, bottom-up estimation) and experimental data (Uexp). This involved characterizing Metformin content in tablets using the Uniformity of Dosage Units (UDU) test as an independent method. The 100 % release of Metformin in the Dissolution test (infinity point) was proved by increasing the dissolution time. Having optimized Dissolution and UDU analytical procedures for variability budget compiling, we achieved insignificance of Uexp compared to the target uncertainty (Utg) for the Dissolution test in compliance testing. The differences in UDU and Dissolution mean results did not exceed UNAP for the release time of 45 and 60 min, i.e. uncertainty budget was proven. Uexp for the Dissolution test indicated the presence of an unknown statistically significant source of random variation, which, however, was less than Utg; therefore, the procedure is suitable for compliance testing.
 Conclusion. Experimental results confirmed the completeness of our knowledge about sources of variation (absence of bias) for the Dissolution test with 100 % release. An essential condition for compiling the budget was the optimization of uncertainty of analytical procedures. For UDU, all significant sources of variation were within the expected range. Yet, there is a need for additional research to identify and manage an unknown source of practically significant random variation for the Dissolution test

The study of some quality parameters and the antioxidant activity of dietary supplements with the pomegranate extract (Punica granatum L.)

Aim. To conduct a qualitative, quantitative analysis and determine the antioxidant activity of dietary supplements with the pomegranate extract. Materials and methods. Three dietary supplements from different manufacturers – “Extract of pomegranate” (manufactured by Source Naturals), “Extract of pomegranate” (manufactured by Puritan Pride), and “Extract of pomegranate” (manufactured by Vitacost) – were chosen for the study. The thin layer chromatography (TLC) was used to perform the qualitative analysis, the quantity of biologically active substances (BAS) in dietary supplements was determined by the spectrophotometric method, the antioxidant activity – by potentiometric method. The qualitative analysis was performed by thin-layer chromatography (TLC); spectrophotometry was used for the quantitative determination, and the potentiometric method was applied to determine the antioxidant activity. Results and discussions. The presence of anthocyanins, flavonoids, catechins and phenolic acids were detected in the dietary supplements analyzed. The total content of phenolic compounds was 201.00 ± 6.03, 159.00 ± 4.77, 110.30 ± 3.30 mg, catechins was 16.10 ± 0.50, 11.60 ± 0.50, 7.33 ± 0.50 mg, anthocyanins was 43 ± 1.29, 32.00 ± 0.96, 22.00 ± 0.66 mg, and flavonoids was 30.15 ± 0.90, 29.44 ± 1.00, 18.21 ± 0.55 mg. The antioxidant activity was 266.11 ± 5.32, 212.12 ± 4.24, 150.81 ± 3.02 mmol-eqv./mextr for dietary supplements “Extract of pomegranate” (manufactured by Source Naturals), “Extract of pomegranate” (manufactured by Puritan Pride), “Extract of pomegranate” (manufactured by Vitacost) in 1 dosage form, respectively. Conclusions. The analysis of the qualitative composition, the quantitative content of BAS and the antioxidant activity of dietary supplements with the pomegranate extract allows us to find out that dietary supplements manufactured by Source Naturals and Puritans Pride meet the requirements of the State Pharmacopoeia of Ukraine (SPhU), while a dietary supplement manufactured by Vitacost does not correspond the requirements. The results of the study allow us to state that the problem of compliance of dietary supplements is relevant; therefore, it is necessary to introduce normative documentation for the identification and determination of BAS in dietary supplements.

Development and technological research of medicated lozenges for catarrhal and aphthous stomatits` symptoms relief

inflammatory diseases of the oral cavity, in particular catarrhal and aphthous stomatitis, create significant discomfort for patients in everyday life. The occurrence of stomatitis in adolescents can be associated with numerous factors: bacterial and viral infection, insufficient oral hygiene, trauma of the mucous membrane, unbalanced nutrition, allergic reactions, some types of systemic diseases etc. Medicated lozenges have advantages for use in adolescents, as they have an interesting appearance (resembling a candy), pleasant taste and aroma, do not require swallowing or washing down with water, release active pharmaceutical ingredients by gradual dissolution in the oral cavity, which ensures their local action. The present work is aimed to develop different formulations of medicated lozenges for catarrhal and aphthous stomatits` symptoms relief. The objects of the study were experimental samples of lozenges with licorice root and propolis extracts. They were chosen as active ingredients due to their antimicrobial properties, as well as their ability to improve the general condition of the periodontium and reduce the outbreak of aphthae in stomatitis. Lozenges were prepared by heating and congealing method using different concentrations of active pharmaceutical ingredients and excipients (candy base substances – sugar substitute (isomalt), glucose syrup, carboxymethyl cellulose). 3 best formulations that had a uniform color distribution and were transparent, not sticky, had no external surface defects were subjects of the development and analysis. Obtained medicated lozenges were evaluated for physical parameters like weight variation, diameter and thickness, and pharmacotechnological evaluations like friability and hardness by pharmaceutical standard methods from State Pharmacopoeia of Ukraine 2.0 (2.9.5, 2.9.7, 2.9.8). Selected samples had homogeneous physical parameters: average weight in the range of 6.98-7.00 g (none of the formulations had a deviation of more than ± 5%), diameter 3.51 cm, thickness 5.04-5.11 mm. The obtained values of hardness and friability (less than 1% for all formulations) indicate satisfactory mechanical strength of the dosage form. Stability study was carried out at (15-25) ⁰С and 60±5 % humidity rate and was determined by evaluating the appearance and pharmacotechnological parameters. The values of hardness and friability were constant throughout the storage period for all formulations. Stability studies indicated that the formulations № 1 and 2 were stable for 30 days. The present research allowed to develop formulations for obtaining a pleasant-tasting dosage form intended for relatively slow dissolution in the oral cavity – medicated lozenges for use in adolescents to alleviate the symptoms of catarrhal and aphthous stomatitis.

Системи якості у фармації: мультидисциплінарний контекст державної фармакопеї України

The multidisciplinary context of the State Pharmacopoeia of Ukraine in drug quality systems was justified through an interdisciplinary study of pharmaceutical business organization, quality control, standardization, drug technology, management, marketing, forensic pharmacy, medical and pharmaceutical law in the system of legal relations "doctor-patient-pharmacist-lawyer" during state formation and implementation of Ukraine's integration processes into the WTO and the EU. Noted that the State Pharmacopoeia of Ukraine was from the first of the CIS countries, fully harmonized with the European Pharmacopoeia, takes into account national specificities, the Constitution of Ukraine, legislation on normative legal acts of Ukraine. Proven that, according to international assessments, the State Pharmacopoeia of Ukraine is the best National Pharmacopoeia in the post-Soviet space concerning the modern requirements of the WTO and WHO regarding quality and safety systems of medicines.

Substantiation of the composition and technology for obtaining combined sustained-release tablets for the treatment of hypertension

Aim. To develop the composition and technology for obtaining the combined drug of indapamide with enalapril of the prolonged action. Materials and methods. Indapamide and enalapril maleate substances as active components, and polyvinylpyrrolidone, calcium stearate, lactose monohydrate, hydroxypropyl methylcellulose as excipients were used. The pharmaco-technological studies were conducted according to the methods of the State Pharmacopoeia of Ukraine (SPhU). Results and discussion. The pharmaco-technological properties of tablet mixtures and the quality of finished tablets were compared using direct pressing and preliminary wet granulation. Conclusions. It has been found that the use of the method of pre-granulation of the tablet mixture allows obtaining a finished product that fully meets the requirements of the SPhU.

THE EXPERIMENTAL DETERMINATION OF THE NUMBER OF FREEZING STAGES OF CANDIDA TROPICALIS FUNGAL CELLS FOR THEIR DESTRUCTION AND OBTAINING OF PROTEINS AND POLYSACCHARIDES

Candidiasis is a disease that occurs due to excessive growth of the Candida fungus. Several types of this pathogen are known, each of which can cause damage to various organs and systems. Recently, there have been reports of the loss of sensitivity of Candida fungi to most of antifungal drugs that have been used for more than 40 years. An alternative to antifungal drugs for candidiasis can be the use of a vaccine for the prevention and treatment of candidal infection. In our opinion, it is promising to use a candidal vaccine based on a subunit vaccine that contains fragments of a microorganism without ballast substances. Cell fragments of Candida fungi that have antigenic properties include proteins and polysaccharides. To isolate antigenic substances from Candida fungal cells, we chose freezing as the method of destruction. The aim of this work was to experimentally substantiate the number of freezing stages for the destruction of C. tropicalis АТСС 20336 fungi cells and the subsequent production of proteins and polysaccharides. To determine the optimal number of freezing stages in the temperature range from (25 ± 2)°С to (-25 ± 2)°С, in order to destroy the cells of C. tropicalis fungi, the studies were conducted with freezing stages 3, 4, 5, and 6. Centrifugation was used to separate the excess components. Then the preliminary and sterilizing filtration was performed on membrane filters with pore diameters of 0.45 μm and 0.22 μm. The content of protein, polysaccharides and monosaccharides were determined in each case. The protein content was determined according to the State Pharmacopoeia of Ukraine (SPhU). To determine polysaccharides, a reaction with phenol and sulfuric acid was performed. Chromatographic studies of monosaccharides were conducted using paper chromatography according to the SPhU. Based on the results of the research, it was found that solutions obtained at stages 5 and 6 of freezing the biomass of C. tropicalis fungi cells at a temperature from (25 ± 2) °C to (-25 ± 2) °C contained the highest amount of proteins and polysaccharides. It is likely that with these number of stages for freezing the biomass of C. tropicalis fungi cells, active substances are released from all layers of Candida fungi cells. Thus, it can be concluded that five stages of freezing are the optimal number that ensures the maximum extraction of polysaccharides and proteins quickly and economically.

The study of the elemental and amino acid composition of Cetraria islandica (L.) Ach. thalli batches harvested in Ukraine

Aim. To study the elemental and amino acid composition of Cetraria islandica (L.) Ach. thalli batches harvested in Ukraine.Materials and methods. Seven batches of C. islandica thalli harvested in different regions of Ukraine in late summer/early fall 2019 were used for the study. The elemental composition of the raw material was studied by atomic absorption spectrometry with photographic registration. The component composition of free and bound amino acids in the raw material was determined by the HPLC method. Results and discussion. The presence of at least 19 macro-, trace and ultra-trace elements was determined in 7 batches of the raw material. The predominance of the following elements was found: potassium 190 mg/100 g (batch 6) – 325 mg/100 g (batch 7); silicon 30 mg/100 g (batch 1) – 115 mg/100 g (batch 4); calcium 37 mg/100 g (batch 6) – 86 mg/100 g (batch 4). It was determined that the quantitative content of molybdenum and cobalt did not exceed 0.03 mg/100 g, the content of cadmium, astatine and mercury did not exceed 0.01 mg/100 g. The quantitative content of lead met the requirements of the monograph of the State Pharmacopoeia of Ukraine (SPhU) 2.0. The total ash content in the batches of the raw material ranged from 0.61 ± 0.02 % to 1.43 ± 0.05 %, meeting the requirements of the monograph of the SPhU 2.0. The presence of 7 amino acids was determined; 5 of them were nonessential (aspartic and glutamic acids, serine, arginine, and alanine) and 2 were essential (threonine and valine). The quantitative content of the total amount of free amino acids was 0.794 μg mg-1, the total amount of bound ones was 3.276 μg mg-1.Conclusions. For the first time, the elemental composition of 7 batches of C. islandica thalli harvested in Ukraine was determined. In each batch, potassium was the predominant element (from 190 mg/100 g to 325 mg/100 g depending on the batch). The component composition of free and bound nonessential and essential amino acids was determined (the quantitative content of the total amount of free amino acids was 0.794 μg mg-1, the total amount of bound ones was 3.276 μg mg-1); alanine (0.289 μg mg-1) was the dominant component among free amino acids, while arginine (0.993 μg mg-1) prevailed among bound ones. The results obtained will be used for further studies of the raw material of C. islandica harvested in Ukraine.

30 років національній системі стандартизації, метрології і контролю якості лікарських засобів в Україні: основні досягнення, проблеми і перспективи розвитку

Provision to every citizen, patient, and person in the system of legal relationship "doctor-patient-pharmacist" the right to life, health, and safety during the circulation of vital medicinal products of all clinical and pharmacological, nomenclature and legal, classification and legal groups, guaranteed by created in in Ukraine the system of standardization and quality control of medicines. The system of standardization and quality control of medicines includes the National System of Standardization of Medicines in Ukraine (1992); The system of state control of the quality of medicinal products (1992); Programs for the development of generic drugs in Ukraine (1995); The school of standardization and quality control of medicinal products; Center for standardization, metrology, and quality control in Ukraine. Ukraine got observer status in the European Pharmacopoeia in 1998. The National Pharmacopoeia of Ukraine (2001) appeared 6-7 years earlier than other countries (Belarus, Kazakhstan, Russian Federation). Two editions of the State Pharmacopoeia of Ukraine, totaling thirteen volumes and 7,208 pages, was developed as of 2022 and put into effect. The State Pharmacopoeia of Ukraine is fully harmonized with the European Pharmacopoeia and is the basis of the entire system of standardization and quality control of medicinal products in Ukraine. A pharmacopeial language (Ukrainian terminological apparatus), which did not exist before, was developed, and implemented. The State Pharmacopoeia of Ukraine is an important reference-informational and educational-methodical material for pharmaceutical enterprises, health care institutions, pharmacies, universities of medical and pharmaceutical profiles. The national system of pharmacopeial standard samples largely meets the needs of national control laboratories, and ranks the 6th in the world in terms of the number of pharmacopeial standard samples. The State Pharmacopoeia of Ukraine is the only pharmacopoeia in the world in which standardized validation procedures have been introduced, which has turned validation into an ordinary routine procedure. Ukraine acquired the status of a full member of the European Pharmacopoeia in 2013. European standards for the quality of medicinal products are in force in Ukraine. The State Pharmacopoeia of Ukraine acquired voting membership in the Pharmacopoeia of the United States in 2010. In order to develop texts that are not in the European Pharmacopoeia (in particular, monographs on ready medicines), the State Pharmacopoeia of Ukraine concluded Agreements with the leading pharmacopoeias of the world – the USA in 2010 and Great Britain in 2013. A powerful market, world- and European-level pharmaceutical industry was created, which was included in the field of health care, which provided the pharmacy network and health care institutions with modern, effective, safe, high-quality, and economically available drugs. The system of legal relations "doctor-patient-pharmacist" is based on the principles of pharmaceutical law, the Constitution of Ukraine, laws, and regulatory acts, timely ensures the right of a person, citizen, and patient suffering from various health disorders in accordance with the ICD-11, on life and health.

Research in components of essential oils from flowers and leaves of the genus Alchemilla L. species

The genus Alchemilla L. has about 1000 species in the world flora, of which 35 grow in Ukraine. The most common in Ukraine are A. flabellata Bus., A. phegophila Juz. and A. subrenata Bus. Despite the widespread distribution of species of the genus Alchemilla L. and the publication of a monograph on the herb of the collective species - Herba Alchemillae (Alchemiilla vulgaris L. sensu latiore) in the State Pharmacopoeia of Ukraine, the chemical composition, and pharmacological properties of species of the genus Alchemilla L. are insufficiently studied, therefore, it is advisable to study the chemical composition of the most common species of flora of Ukraine for their introduction into medical and pharmaceutical practice.
 The aim of the work was to study the component composition and quantitative content of essential oils of flowers and leaves of some species of the genus Alchemilla L.
 Materials and methods. Flowers and leaves of Alchemilla. flabellata Bus., Alchemilla phegophila Juz. and Alchemilla subrenata Bus. harvested in the Ivano-Frankivsk region in 2020 - 2021.
 The component composition and quantitative content of essential oils were determined by chromato-mass spectrometric method. The compounds were identified by comparing the obtained mass spectra of the chromatographic peak with the mass spectra of the reference compounds and based on comparison with the spectra of the database. Quantitative determination of the content of substances in the raw material was performed in comparison with a standard sample of menthol.
 Results. The essential oil of flowers and leaves of Alchemilla. flabellata Bus., Alchemilla phegophila Juz. and Alchemilla subrenata Bus were obtained. It was found that the highest content of essential oils was characterized by Alchemilla. flabellata Bus. flowers (16884.6 mg / kg), and the least essential oil was contained in the leaves of Alchemilla Phegophila Juz. (4895.5 mg / kg). As a result of studying the component composition of essential oils of flowers and leaves of Alchemilla flabellata Bus., Alchemilla Phegophila Juz. and Alchemilla subrenata Bus. 48, 51 and 47 compounds were identified, of which 44, 48 and 43 were identified, respectively. 31 components of essential oil were common in the studied samples of raw materials.
 Conclusions. Due to the component composition of the essential oil of flowers and leaves of Alchemilla. flabellata Bus., Alchemilla phegophila Juz. and Alchemilla subrenata Bus., as well as considering the known pharmacological activity of its components, it is advisable to conduct further pharmacological studies of raw materials of the genus Alchemilla L. to study their antibacterial, anti-inflammatory and antitumor properties

Establishment of quality indicators of promising plant raw materials - underground organs of Rumex confertus willd

The aim is to study the morphological and anatomical structure of the underground organs of R. confertus and to establish the type of medicinal plant raw materials, to determine a number of its indicators of quality and quantitative content of some groups of biologically active substances using modern methods of analysis.
 Materials and methods. It was used air-dry and freshly collected raw materials and a microscope Delta optic BioLight 300 (Poland) to study the macro- and microscopic characteristics of the plant raw materials. Determination of amount of hydroxycinnamic acids and total polyphenols was determined spectrophotometrically according to monograph «Nettle leaf» and the method 2.8.14 of the State Pharmacopoeia of Ukraine 2.0 (on a spectrophotometer Optizen POP (Korea)). The study of the component composition of hydroxycinnamic acids was performed by HPLC.
 Results. As a result of research of plant raw materials it was established that the underground organs of Rumex confertus are the roots of annual plants and the rhizomes and roots of two or three annual plants. Diagnostic features: morphological (for the root and rhizome - the nature of the surface and fracture) and anatomical (for the rhizome - aerenchyma in the cortex, the presence and location of scleroids and sclerenchyma in the plant raw materials of two or three annual plants, the presence in the cells of the cortex and pith parenchyma simple starch grains, druses and cells with yellow content in freshly harvested plant raw materials; for the root - the colour of peridermal cells, the degree of development of pith rays, the remainder of the primary xylem; a distinctive feature of the annual root from two or three annuals is the absence of scleroids). It was determined the borderline boundaries of indicators in the series of plant raw materials: loss on drying (not more than 13. 5 %), total ash (not more than 11 %), extractable matter (not less than 33 %) and the quantitative content of amount of hydroxycinnamic acids (not less than 1.3 %) and total polyphenols (not less than 3.5 %). It was identified chlorogenic and neochlorogenic acids.
 Conclusions. It was determined the type of underground organs of Rumex confertus: annuals had only roots (tap root systems), from the second to the third year of life the plants have both rhizomes and tap root system. It was established their morphological and anatomical diagnostic features and determined numerical indicators and the quantitative content of the amount of hydroxycinnamic acids and total polyphenols with using modern methods of analysis and chlorogenic and neochlorogenic acids were identified. The obtained data will be used in further research, including the development of the draft monograph of the State Pharmacopoeia of Ukraine 2.0 or the draft methods of quality control of medicinal plant raw materials Rumex confertus and the creation of herbal medicines

The quantitative content determination of main groups of biologically active substances in batches of Viburnum opulus fruits

Aim. To determine the quantitative content of the main groups of biologically active substances (BAS) in batches of Viburnum opulus fruits using pharmacopeial methods for their subsequent use in the standardization of the plant raw material.Materials and methods. For the study, 6 batches of air-dried Viburnum opulus fruits crushed to a particle size of 1 – 2 mm and harvested in different regions of Ukraine in the mass fruiting phase in October-November 2020 were used. The quantitative determination of polyphenols and tannins was performed using the spectrophotometric method at a wavelength of 760 nm calculated with reference to pyrogallol and dried substance. The total amount of hydroxycinnamic acids was determined according to the method of the SPhU (State Pharmacopoeia of Ukraine) 2.0 described in the monograph “Kidney TeaN” calculated with reference to rosemary acid. The total amount of organic acids was determined by the titrimetric method according to the method of the monograph of the SPhU 2.1 “Rose hipsN” calculated with reference to malic acid.Results and discussion. The quantitative content of polyphenols (calculated with reference to pyrogallol and dried substance) in batches of Viburnum opulus fruits varied by about 1.4 times from 1.74 ± 0.01 % to 2.36 ± 0.01 %. According to the results obtained, the quantitative content of tannins (calculated with reference to pyrogallol and dried substance) in batches of Viburnum opulus fruits varied by 1.7 times from 0.73 ± 0.01 % to 1.23 ± 0.01 %. The quantitative content of the total amount of hydroxycinnamic acids calculated with reference to rosemary acid in batches of Viburnum opulus fruits ranged by 1.2 times from 3.96 ± 0.01 % to 4.73 ± 0.01 %. The quantitative content of the total amount of organic acids calculated with reference to malic acid in batches of Viburnum opulus fruits fluctuated more than 1.3 times from 6.80 ± 0.01 % to 9.08 ± 0.01 %.Conclusions. The quantitative content of the main groups of biologically active substances has been determined in 6 batches of Viburnum opulus fruits harvested in different regions of Ukraine using pharmacopoeial methods: polyphenols (varied by 1.4 times), tannins (varied by 1.7 times), the total amount of hydroxycinnamic (varied by 1.2 times), and the total amount of organic acids (varied by 1.3 times) calculated with reference to dried substance. The content of the groups of biologically active substances in batches of Viburnum opulus fruits slightly correlates with the place of the raw material harvesting. Thus, the selected methods of the SPhU 2.0 are quite suitable for determining the quantitative content of polyphenols, tannins and of the total amount of hydroxycinnamic and organic acids in batches of Viburnum opulus fruits; they can be used in further studies to standardize the raw material.

Research of technological properties of Medicinal Plant raw material of Siberian Statice (Limonium gmelinii)

the article presents the results of studying the technological properties of medicinal plant raw materials Siberian Statice (Limonium gmelinii), namely specific, volumetric, bulk density, determination of absorption coefficient and swelling rate, as well as porosity, free volume layer and fractional composition. Grinded raw materials from the aboveground part of Siberian Statice, which included stems, inflorescences, flowers was the object of the study. Siberian Staticea (Limonium gmelinii) is a perennial herbaceous bare plant of the Kermek genus, which contains tannins, flavonoids, hydroxycinnamic acids, anthocyanins, coumarins, carbohydrates, polysaccharides, organic acids, amino acids and others. The raw material in the Genichesk district of the Kherson region was harvested in 2021. The study of basic technological properties was carried out according to generally accepted methods, which are listed in the State Pharmacopoeia of Ukraine. The data obtained during the study indicate that the composition of the grinded raw material is polydisperse and it is not possible to determine one predominant fraction. Particles with a size of 2,8-1,0 mm are about 80% of the composition. This diversity of composition can be explained by the fact that the studied aboveground part of plant raw materials includes a thick-branched stem, inflorescences with small regular flowers. The humidity of the studied raw materials is 0,23%. The specific density of raw materials is 1,3446 ± 0,0073 g/cm3, and the volumetric density of plant raw materials is 0,4679 ± 0,0450 g/cm3. Bulk mass after shrinkage decreased from 80 to 69, which is 13,75%. Volumetric shrinkage increased from 0,1251 g/cm3 to 0,1436 g/cm3. Indicators of porosity, porosity and free volume layer (0,6933 g/cm3, 0,7326 g/cm3, 0,9073 g/cm3, respectively) are quite high, which indicates a good absorption capacity of raw materials. The average value of the absorption coefficient was 6,33 ± 0,34, which indicates a high cost of extractant, and the swelling rate shows that the investigated raw material doesn’t swell, this indicates the presence of pores inside the stem, where the extractant is retained, but does not increase linear dimensions and volume plant raw materials. The technological properties of Siberian Statice (Limonium gmelinii) raw materials have been experimentally determined, which allow choosing the optimal extraction methods for the studied raw materials, namely the extraction method, the ratio of raw materials: extractant, the nature of the extractant.

Validation of Amoxicillin iodometric procedure in quantitative analysis of pure substance and medical preparation

The aim of the work is to validate a simple and rapid iodometric procedure for the quantitative determination of amoxicillin in pure substance and medicinal preparation using potassium caroate as analytical reagent. Materials and methods. The procedure involves the use of potassium caroate (KHSO5) as an oxidant. The assay is based on the quantitative penicillin oxidation by KHSO5 to the corresponding S-oxide. The interaction between amoxicillin and analytical reagent is stoichiometric. Indirect iodometric method is used for the quantitative determination of amoxicillin main substance. The validation procedure was performed according to the State Pharmacopeia of Ukraine. Results. The precision, accuracy, limit of detection (LOD), and limit of quantitation (LOQ) are accepted over the concentration range of 80–120 % with a correlation coefficient of 0.999. LOD and LOQ were found to be 4.91 % and 14.73 % for amoxicillin pure substance respectively. The precision calculated as the relative standard deviation (RSD) was less than 0.8 % and accuracy (δ, relative error) was better than 0.4 %. The proposed method was validated statistically and through recovery studies. For Amoxicillin medical preparation RSD ≥1.93 % and δ ≥ 1.62 %. Conclusions. The obtained data showed acceptable agreement with the certificate results, so the proposed procedure can be used for the assay of amoxicillin in medicinal preparation.

Development the composition and technology for obtaining a dietary supplement “Cachinol” with the antioxidant activity in the form of granules used in the polycystic ovary syndrome

Aim. To develop the composition and technology for obtaining a dietary supplement “Cachinol” with the antioxidant activity in the form of granules used in the polycystic ovary syndrome. Materials and methods. To achieve the goal, physical, physicochemical, pharmacotechnological and statistical research methods, as well as generally accepted research methods of the State Pharmacopoeia of Ukraine (SPhU) 2.0 were used in the work. Results and discussion. The rational dosage form is granules. The green tea leaf extract and myo-inositol were chosen as the active pharmaceutical ingredients of granules. For 3 batches of granules, the following parameters were determined: the fractional composition ranging from 13.2 to 17.9 % for 3-2 mm, from 45.3 to 56.2 % for 2-1 mm, from 20.1 to 26.1 % for 1-0.5 mm, from 8.1-12.4 for 0.5-0.25 mm, from 2.95-4.6 % for < 0.25 mm; the moisture content of granules ranging from 2.80-3.10 %; the bulk density – from 0.49 to 0.52 g/cm3, the tapped density – from 0.54 to 0.58 g/cm3; the flowability was in the range of 8.00-8.25 g/s; the angle of repose – from 30 to 33°; disintegration – from 41 to 45 s. Conclusions. The flowchart for obtaining granules in industrial conditions has been developed. The technological process for obtaining granules consists of 8 technological stages. The studies of the technological parameters of granules have been performed in accordance with the requirements of the SPhU 2.0. It has been found that the granules developed meet the requirements of the SPhU 2.0 and can be recommended for further research.

Improvement of the pharmacopoeial identification of burr marigold herb by macro- and microscopic characteristics

Aim. To improve the national monograph of burr marigold (Bidens tripartita L.) herb on macro- and microscopic characteristics of the raw material. To achieve this goal, a comparative macroscopic analysis of various species of burr marigold and an extended microscopic analysis of all parts of the plant that are part of the raw material were carried out. Materials and methods. The study objects were 7 samples of the medicinal plant raw material of Bidens tripartita L. identified and registered at the premises of the State Enterprise “Pharmacopoeia Center”. They were provided by various domestic manufacturers; a sample of the whole raw material of B. frondosa L. collected in the Akhtyrsky district ofthe Sumy region; a sample of the whole raw material of B. cernua L. provided by a domestic pharmaceutical enterprise. The raw material was harvested in the period of budding and the beginning of flowering. The dry raw material wassubject to the macroscopic analysis. The microscopic analysis was performed on the powder of the raw material sifted through a sieve with a hole diameter of 355 since according to the requirements of the European Pharmacopoeia and the State Pharmacopoeia of Ukraine this was a standardized procedure for determining the diagnostic signs of the medicinal plant raw material by microscopy. Results and discussion. As a result of the macroscopic analysis, it has been found that the raw material of Bidens tripartita L. is a mixture of the whole or fragmented stems with leaves, leaves, anthodia, and achenes. Stems are green or greenish-purple, round-oval, longitudinally grooved. Leaves are green or brownish-green, with a dentateserrated edge, opposite, with a 3-5-parted lamina with lanceolate lobes narrowed into short, slightly winged petioles. Inflorescences are erect anthodia, their width is almost equal to the height. Fruits are flattened achenes, at the apex with 2 or 3 awns, twice as short as the achene. The awns and lateral ribs of the achenes are covered with bristles, which tips are directed downwards. As a result of the microscopic analysis of Bidens tripartita L. powder, diagnosticsigns of all parts of the raw material have been found, namely: fragments of the lamina with veins, along which secretory channels with reddish-brown contents pass; fragments of the lamina from the upper or lower epidermis with the basic cells with sinuous walls, stomata anomocytic type, covering caterpillar form trichomes of 9–18 thin-walled cells, rarely thick-walled covering trichomes of 2-13 cells; fragments of the stem epidermis of rectangular elongated cells with thickened walls; fragments of the epidermis of the inner leaves of the involucres of elongated rectangular thin-walled cells and articulated branched secretory channels; fragments of epidermis of tubular flowers from polygonal cells with rounded papillary outgrowths; rounded pollen grains with spinous exine; fragments of the testa with pigmented darkbrown cells of the hypodermis and the adjacent lower layer of elongated yellowish sclereids. Conclusions. The sections “Identification A and B” (macro- and microscopic signs of the raw material) of the national monograph “Burr marigold herbN” of the SPhU 2.2 have been improved, and it allows to more accurately identify all parts of the medicinal plant raw material. The additions developed are included to the SPhU 2.5 in the text of the monograph “Burr marigold herbN”.

Development of a methodological approach to determine regression equations in the study of the technology for manufacturing tablets based on quercetin

When developing the technology of tablets and tablet masses one of the tasks is to determine the amounts of excipients required to obtain pharmaco-technological quality indicators that meet the requirements of the State Pharmacopoeiaof Ukraine (SPhU). Aim. To develop an algorithm for determining the type of three-factor mathematical models with dependent variables. Materials and methods. The study object was experimental observations of the quantitative effect of excipients in the tablet composition based on a solid dispersion of quercetin on the pharmacopeial characteristics of this dosage form, in particular on its flowability. The experimental data were processed by the planned experiment using Mathcad 15 and MS Excel software according to the algorithm proposed. Results and discussion. It has been found that the identification of mathematical models in pharmaceutical studies with three dependent factors, which total value is determined by the quantitative composition of the dosage formand fixed at a certain level, is difficult to perform due to the difficulty of interpreting the multiple regression parameters as characteristics of factors in isolation through their correlability. It has been proven that the replacement of variablesleads to the determination of a mathematical model that does not reveal the mechanism of the factors’ action and is a static description of their overall impact on the indicator studied. Conclusions. As a result of the research conducted, regression equations were found to determine the effect of the amount of these excipients on the tablet flowability. It has been found that the most influential role in determining the target in the factor space studied is played by the interaction of factors. The algorithm for determining the mathematical description of the dependence with three variables has been proposed. Based on the fact that the research is conditioned by strict conditions in the quantitative composition, the chosen mathematical model of the dependence of the quadratic equation with two factors, for which there are limitations, has no correlation. The model determined is characterized by the possibility of providing the graphical interpretation and simplification of analysis and can be used for forecasting and optimization.

Study of compatibility of components of a new combined drug for treatment of alcoholic intoxication and its hepatoprotective effect on a model of alcoholic liver injury

The aim of the work is the development of a combined drug for use in alcohol intoxication based on the physicochemical properties and chemical compatibility of active pharmaceutical ingredients and excipients, and the study of the hepatoprotective effect in alcoholic hepatitis in rats. Materials and methods. During the studies, physical and physicochemical methods were used, a Specord 200 spectrophotometer (Germany), analytical scales Sartorius (SARTORIUS, Germany), class A volumetric glassware and reagents that meet the requirements of the State Pharmacopoeia of Ukraine (SPhU). Alcoholic hepatitis in rats was reproduced by intragastric administration of an aqueous 40% ethanol solution at a dose of 7 ml/kg for 1 week. Results. A new combined agent is proposed for use in alcohol intoxication in the form of an effervescent powder for the preparation of an oral solution, which contains glycine, L-glutamic acid, acetylsalicylic acid, ascorbic acid, fructose / sorbitol and sodium bicarbonate and citric acid to accelerate the dissolution of medicinal substances. To study the compatibility of the components, experimental studies of hygroscopicity, chemical interaction / chemical stability and an assessment of the redox potential of the proposed active pharmaceutical ingredients were carried out. To study the stability of the API, studies were carried out on sugaramine condensation due to the choice of amino acids and ascorbic acid in the composition of drugs. Based on the research results, it was decided to divide the API into 2 packages, separating sodium bicarbonate and glycine, which can interact with ascorbic acid / acetylsalicylic acid and ascorbic acid, respectively. In an in vivo experiment, it was found that the use of the new drug is accompanied by the normalization of the antioxidant-prooxidant status of the liver due to a likely decrease in the TBA-AP level and an increase in the RG index in the liver homogenate relative to the control group. Conclusions. Evaluation of the physicochemical properties of API allowed us to propose a new combined drug (TS-PP) for use in alcohol intoxication in the form of an effervescent powder for the preparation of oral solution. In alcoholic hepatitis in rats, it was found that the use of the studied drug largely prevents the formation of the effects of the toxic effects of ethanol on the rat organism, which is manifested by inhibition of destruction of hepatocyte membranes, a decrease in the level of LPO products, restoration of the RG index and improvement of the protein synthesizing function of the liver due to the complex effect of amino acids and ascorbic acid contained in the product

Selection of the optimal extractant for the extraction of phenolic compounds from Laurus nobilis L. leaves

Aim. To select the optimal extractant for the extraction of a number of groups of phenolic compounds from Lаurus nоbilis L. leaves based on the determination of the quantitative content of these groups in the extracts obtained. Materials and methods. Lаurus nоbilis L. leaves were harvested in November 2020 from artificially cultivated specimens aged 5 – 7 years. The quantitative determination of polyphenols was performed using the spectrophotometric method at a wavelength of 760 nm in accordance with the requirements of the Supplement of the State Pharmacopoeia of Ukraine (SPhU) 1.2 (2.8.14). The quantitative content of this group of compounds was calculated with reference to pyrogalol and dried substance. The quantitative determination of the amount of hydroxycinnamic acids was performed according to the SPhU 2.2 monograph “Orthosyphon stamen (kidney tea) leavesN” by the spectrophotometric method at a wavelength of 505 nm and calculated with reference to rosmarinic acid. The quantitative determination of the amount of flavonoids was performed according to the SPhU 2.0 monograph “Hawthorn leaves and flowers” by the spectrophotometric method at a wavelength of 410 nm and calculated with reference to hyperoside.Results and discussion. The analysis of the results for the quantitative determination of polyphenols, the amount of hydroxycinnamic acids and the amount of flavonoids in extracts from Lаurus nоbilis L. leaves obtained using water, water-ethanol mixtures and 96 % ethanol showed that 70 % ethanol was optimal for extracting compounds of these groups. The quantitative content of polyphenols (calculated with reference to pyrogalol) was not less than 21 %, the amount of hydroxycinnamic acids (calculated with reference to rosmarinic acid) – not less than 3 %, the amount of flavonoids (calculated with reference to hyperoside) – not less than 5 %. Conclusions. For the first time, the quantitative content of a number of groups of phenolic compounds (polyphenols, the total amount of hydroxycinnamic acids, and the total amount of flavonoids) in Lаurus nоbilis L. leaves extracts obtained using various extractants has been determined. On this basis, the optimal extractant – 70 % ethanol for the extraction of phenolic compounds has been selected. The results obtained will be used when developing the technology for obtaining substances from Lаurus nоbilis L. leaves.