State Pharmacopoeia Of Ukraine Research Articles

THE STUDY OF THE EXTRACTION DYNAMICS OF BIOLOGICALLY ACTIVE SUBSTANCES FROM THE BIDENS TRIPARTITA L. HERB AND ANTIOXIDANT ACTIVITY OF THE OBTAINED EXTRACTS

The interest to study the genus Bidens and in particular Bidens tripartita L. (bur-marigold herb) is unmitigated due to its antioxidant, anti-allergic, antimicrobial, antifungal, hepatoprotective, immunostimulating and hypotensive activity. This pharmacological activities are determined by the presence of flavonoids, polyphenolic compounds, polysaccharides, components of essential oils, polyacetylenes, etc. The aim of the research was to study the process of extracting various biologically active substances (polysaccharides, flavonoids, polyphenols) from bur-marigold herb with water-alcohol mixtures of various concentrations, to study their component composition, as well as to evaluate their effect on the oxidative effect of free radicals. Materials and methods. The object of the research was the herb of Bidens tripartita L. Raw materials were collected and procured on the territory of Kharkiv, Zhytomyr and Poltava regions of Ukraine. All used methods for the quantitative determination of biologically active substances were pharmacopeial and described in various monographs in the European Pharmacopoeia and State Pharmacopoeia of Ukraine. Results. The extracts of the bur-marigold herb were analyzed for the content of the extractable matter, flavonoids, polysaccharides and it was found that they are maximally extracted (about 80 %) in the 1st percolate with a drug/solvent ratio of 1:10 for all the extractants. It was found that with an increase of ethanol concentration in the extraction mixture, the content of polyphenols and flavonoids, is expectedly increased, as well as the value of the antioxidant activity of the corresponding extracts, but the amount of extracted polysaccharides is significantly reduced. Conclusions. With the selected evaluation criteria, it was found that 40 % ethanol is optimal from the point of view of balanced extraction of flavonoids, polysaccharides and polyphenols. A strong positive and statistically significant correlation was found between the content of polyphenols in the obtained extracts and their antioxidant activity (Pearson correlation coefficient, r=0.9998), slightly weaker for flavonoids (r=0.9886), and an inverse correlation between polysaccharides content and TEAC- value.

Quantification of albendazole in tablets of combined composition

The Aim: Treatment of helminthiases of the digestive system remains an actual task of the medicine and pharmacy worldwide. So, to meet the needs of the Ukrainian pharmaceutical market tablets based on albendazole and praziquantel were proposed. In order to establish the further production of the drug, studies were conducted on the development and validation of a method for the quantitative determination of one of the active substances – albendazole, in the presence of the second active substance praziquantel. Materials and Methods: The object of the study was samples of tablets under the conditional name “AP-helmin”. Albendazole was extracted from tablets with ethyl alcohol when heated, 0.1 M sodium hydroxide solution was added and the obtained sample was evaluated spectrophotometrically in the ultraviolet light (308 nm). The method was conducted meeting the requirements of State Pharmacopoeia of Ukraine, harmonized with the relevant European Pharmacopoeia techniques. Results: The samples comply with the Bouguer-Lambert-Behr law in the concentration range 1 × 10-3 - 1.2 × 10-2 mg/ml, the correlation coefficient is ≥ 0.9998. The studied method of quantitative determination of albendazole in the drug meets the criteria of acceptability for the range of determination ± 5.0 % by validation characteristics: specificity, linearity, precision, accuracy. The criterion of insignificance of the systematic error of the method is fulfilled – the systematic error of the method (0.24) is practically insignificant, that is, the method of analysis is characterized by sufficient correctness in the whole concentration range from 80 to 120 %. All the validation characteristics respond to the acceptance criteria. Conclusions: A method for the quantitative determination of albendazole in tablets “AP-helmin” by spectrophotometry in ultraviolet light (308 nm) was worked out. It was experimentally confirmed that the second active pharmaceutical ingredient (praziquantel) had no affect the accuracy of the results obtained.

A study of the influence of the test sample inhomogeneity on variability in assay results of desloratadine in film-coated tablets

Aim. The work aimed at metrological evaluation and management of the risk of inconsistency in the results of desloratadine assay in film-coated tablets.Materials and methods. A pilot-scale batch of the pharmaceutical preparation Alerdez served as a study object. Spectrophotometric readings were performed on a UV-Vis spectrophotometer Lambda 25 at 282 nm. An analytical balance Mettler Toledo, pH-meter Metrohm, Class A volumetric pipettes and flasks were used for analysis. The test sample was prepared by manual tablet grinding.Results and discussion. A trend of obtaining inconsistent assay results with a systematic shift towards an increase while taking test portions in sequence was observed. This may inform a test sample inhomogeneity, which may be reduced by increasing a test portion mass. An experiment design to study the impact of the test portion mass on the variability in assay results was laid down. A prognosis for the minimum test portion mass contributing to the mitigation of the risk of the test sample inhomogeneity was scientifically justified and experimentally verified. Acceptance criteria for the assessment of the test sample homogeneity by assay results were established based on the principle of insignificance and recommendations of the State Pharmacopoeia of Ukraine to the target measurement uncertainty. A procedure for desloratadine assay intended to be used for the method transfer and routine analysis, as well as acceptance criteria for assay results, was developed. Their feasibility was experimentally proved during method transfer. The greater difference between the values obtained in the receiving unit compared to those collected in the sending unit was observed, yet the results met the acceptance criteria.Conclusions. This paper provides comprehensive solutions that allow for minimizing the risk of variability in desloratadine assay results. The risk of aberrant assay results could be mitigated by using a test portion equivalent to the weight of four tablets (approx. 420 mg)

Development of harmonized HPTLC methods for determination of polyphenolic compounds of tinctures

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.

Legal differentiation in the case of domestic legislative default in the field of intellectual property for medicines

Within the framework of this article, it is pointed out the importance of legal order in the created domestic regulatory and legalframework of intellectual property for medicines on the basis of international legislation, implemented by approximating national le -gislation to the norms of the European Community law in this area. The disadvantages of the standard approaches of Ukrainian lawmakingin the intellectual pharmaceutical industry to the transformation of legal experience in the pharmaceutical industry of the EuropeanCommunity, which give rise to the domestic legislative default, are presented.Impartially considered the impact of the lack of clarity of the current legislation on intellectual property in pharmaceuticals onthe formation of legally defective, with protective and protective helplessness, intellectual property objects for medicines, which are amanifestation of the legal incompetence of national legislators.The negligent attitude of domestic legislators to the uncertainty in the content of the above changes to the laws that have a directimpact on the definition of the concepts of intellectual property objects for medicines, forms a deformed regulatory and legal basis forpatenting in this area – the ground for possible violations in the form of patent trolling, counterfeit pharmaceutical products, corruptionschemes in medicine, unfair competition, falsification of drugs, and the like, where, first of all, the safety, quality and effectiveness ofdrugs are leveled.The importance of legal differentiation and the need for legal sorting, the renewal of the national legal system to consolidate thesystem of legal regulation of the intellectual pharmaceutical industry by increasing the transparency of the pharmaceutical market andthe responsibility of its participants are noted.Indicated on the negligent attitude of domestic lawmakers to the uncertain classification of inventions in pharmaceuticals, which,like the above definitions of the concepts of intellectual property for medicines, forms a deformed regulatory framework for patentingin this area – the basis for possible offenses in the form of patent trolling, counterfeit pharmaceutical products, corruption schemes inmedicine, unfair competition, falsification of drugs, etc., where, first of all First, the level of safety is leveled, as are the spines andeffectiveness of drugs. At the same time, it should be noted that the lack of results of proper judicial practice in the field of intellectualproperty for medicinal products is an indicator of non-functioning legislative mechanisms for the transformation of the European legalsystem into a national regulatory framework.
 The importance and necessity of restoring ecological pharmacies to consolidate the system of legal regulation of the intellectualpharmaceutical industry by increasing the transparency of the pharmaceutical market and the responsibility of its participants is indicated.In our opinion, the legislation in this priority for the state strategy area should be reviewed to eliminate recurrences and contradictionsbased on the implemented system of monitoring, competent legal analytics and control of compliance of Ukrainian legislationwith EU legislation. In turn, a well-functioning, fully documented pharmaceutical quality system must be developed that should includeGood Manufacturing Practices (GMPs) with quality control and risk management for quality at the stage of intelligent product creation.Thus, the underestimated pharmacy business, where extracorporeal medicines created in the conditions of individual production(manufacturing) with ensuring compliance with their purpose, the requirements of regulatory (analytical, technical, technological) do -cu ments, the State Pharmacopeia of Ukraine, and exclusion of risks for patients, may unreasonably have features patentability, basedon international experience, as a manifestation of relevant medicine.

OPTIMIZATION OF LIQUID CHROMATOGRAPHIC CONDITIONS TO SEPARATE WATER-SOLUBLE VITAMINS

Vitamins are widely used in veterinary medicine, in particular, as components of premixes, feeds and feed additives to increase the productivity of farm animals. Most of these feed additives are a complex amino acid and vitamin mixtures (of ten active substances or more) based on the matrix of plant or animal origin, which can be enriched with protein. When the analyst is faced with the difficult task of analyzing such a mixture, it is usually necessary to use several variants of the HPLC method (high-performance liquid chromatography), which increases the time and cost of analysis of the premix or feed additive. The aim of this work was to optimize the validated method of analysis of riboflavin in premixes and feed additives available in the laboratory for simultaneous (during one chromatographic separation) determination of the content of the maximum amount of water-soluble vitamins. A Waters liquid chromatograph equipped with an Alliance 2690 separation module with a PAD 996 diode array detector was used for separation. Water-soluble vitamins were separated on a Luna Omega Polar C18 250 × 4.6 mm, 5 μm chromatographic column. As solvents were used 0.05 M phosphate buffer pH 3.0 and 0.1 M sodium hydroxide solution (for folic acid).
 The article describes the stages of liquid chromatographic separation parameters optimization of twelve vitamins and vitamin-like substances (thiamine hydrochloride, riboflavin, flavin mononucleotide phosphate, nicotinic acid, nicotinamide, calcuim pantothenate, phosidinobacino acidorinolobin, hydrocyanide). Chromatograms of standard samples solutions are given, which show the specificity of the technique. Isocratic and gradient elution schemes are investigated. Some parameters of chromatographic peaks under conditions of gradient separation of vitamins are estimated. The parameters of the chromatographic peaks do not exceed the limits recommended in the State Pharmacopoeia of Ukraine (SPU 2.0), that will allow to further carry out a more complete validation of the method for quantitative determination of water-soluble vitamins in various complex matrices: injection and oral solutions, feeds and premixes.

Optimization of tablet formulation containing ginger dry extract

Abstract Introduction. Diabetes mellitus is one of the world’s most common diseases, therefore the development and introduction of new effective drugs for diabetes treatment into clinical practice is an important task for the health systems of many countries of the world. Aim. The aim of our work was to determine and substantiate the quantitative ratio of excipients for the development of the optimal composition of directly compressible ginger dry extract tablets. Materials and methods. To choose the optimal composition of tablets containing ginger dry extract, the effect of various quantitative ratios of the excipients Kollidon K30 and Neusilin UFL 2 on tablet mass pharmaceutical technical parameters, determined by established methods, was studied. For processing the experimental data, mathematical methods were used: design of experiment, regression analysis and a technique based on the theory of vector optimization. Results. The interrelation between factors that were studied and technological parameters of tablet mass and compressed tablets were analyzed using regression equations. Conclusions. The studies conducted allowed to chose the optimal composition of ginger dry extract tablets: ginger dry extract – 60%, Galen IQ 721 – 34.5%, Kollidon K30 – 3.5%, Neusilin UFL 2 – 1%, calcium stearate – 1%. The chosen tablet formulation is characterized by pharmaceutical technical parameters meeting the requirements of the European Pharmacopoeia and the State Pharmacopoeia of Ukraine.

DETERMINATION OF OPTIMAL EXTRACTION CONDITIONS OF PHENOLIC COMPOUNDS FROM ACORUS CALAMUS LEAVES

From the beginning of its existence and until now, interest in herbal remedies has only grown. Not surprisingly, medicinal herbs are a source of unique combinations of biologically active components that are capable of exhibiting significant pharmacological effects. One of these medicinal plants is Acorus calamus (sweet flag), whose rhizomes have long been used in official and folk medicine, cooking and cosmetology. However, recent studies point to the considerable potential of the aerial part of Acorus calamus as a novel herbal remedy, which is associated with the presence in the leaf of the plant, in addition to essential oil, a considerable amount of substances of phenolic nature. The aim of the research was to determine the optimal conditions for the removal of phenolic compounds from the leaves of Acorus calamus and to determine the technological parameters of raw materials. Materials and methods. During the research, samples of raw materials collected on the territory of Kharkiv region were used, as well as methods that are given in the State Pharmacopoeia of Ukraine. Result. As a result of the research, the extraction conditions at which there was highest content of the extraction of biologically active substances were determined. The extractant, the degree of grinding of the raw material and the optimum extraction time were selected, which allowed to extract almost 80 % of the quantitative content of flavonoids from the raw material. The main technological parameters of Acorus calamus leaves were also determined. The obtained results will be the basis for the development of the technology of obtaining phyto-substance from the leaves of Acorus calamus. Conclusions. The selection of optimal extraction conditions of biologically active compounds from Acorus calamus leaves was carried out. The obtained results show that in order to obtain extracts with the maximum content of biologically active substances (flavonoids), it is advisable to use raw materials with a particle size of 0.5 to 1.0 mm, as an extractant 70 % alcohol and an extraction time of 4 hours.

Substantiation of production technology of tablets “AP-helmin”

The aim. The purpose of this work is to substantiate the technology of “AP-helmin” tablets preparation and to establish the possible critical parameters of the production process.Materials and methods. Objects such as a mixture of pure substances albendazole and praziquantel in the ratio (1:4), tablet mass and tablet core samples were used in the research. The usual physicochemical and pharmacotechnological methods of the State Pharmacopoeia of Ukraine were used in the work, namely, the appearance, physical parameters, bulk density, compressibility, flowability, crushing force, determination of average mass, uniformity of mass, resistance to crushing and disintegration time were evaluated.Results. It was found that the mixture of active substances has poor flowability, indicating the need to enter the stage of wet granulation in the development of tablet technology with them.The wet granulation stage was carried out with the addition of such excipients as corn starch, microcrystalline cellulose 101 (MCC-101) and povidone (as a 10 % solution).Studies of the 4 samples of tablet mass allowed establishing the most rational composition for the formation of tablets-cores – sample number 4. The samples of composition No. 4 are white core tablets, homogeneous, without chips and cracks, and with respect to resistance to crushing and disintegration time meet the requirements of SPhU (96 N and 8 min 27 sec, respectively).The next stage of the study was the development of a common technology for the preparation of the tablets “AP-helmin”. In order to ensure proper consumer characteristics, the Opadry II ®YS-1-7027 White ("Colorcon") white coating was introduced.Conclusions. On the basis of the obtained results, a technological scheme of production was prepared taking into account the critical parameters and the forecasted control methods at different stages

RESEARCH ON THE SELECTION OF EXCIPIENTS AS THE RATIONALE FOR THE COMPOSITION OF THE TABLETS WITH DRY EXTRACT OF SANGUISORBA OFFICINALIS

The aim. The aim of the research was to study the effect of different groups of excipients on the pharmaco-technological propertiesof the powder mass for tabletting in the development of the composition of the tablets with dry extract of Sanguisorba officinalis for complex therapy of the gastrointestinal tract diseases. Materials and methods. Objects of study - dry extract Sanguisorba officinalis, 25 excipients used in the production of tablets by the method of direct compression, grouped into five groups of factors (fillers based on sugars and microcrystalline cellulose, disintegrants, glidants and lubricants), samples of powder masses. Studies on the determination of pharmaco-technological properties (fluidity, bulk density, bulk density after shrinkage, degree of compressibility, Hausner ratio, and angle of repose) of the obtained powder masses were carried out according to the methods of the State Pharmacopoeia of Ukraine, Second edition. The method of mathematical planning of the experiment was used in the work, the obtained results were subjected to variance analysis, and the ranked series of advantages were placed, in which the excipients were placed in the sequence of their influence on the studied pharmaco-tecnological parameters. Results and discussion. The influence of excipients (factors) on the pharmaco-technological properties (responses) of the powdered tablet masses with the construction of ranked benefits was studied using a five-factor experiment, a hyper-Graeco-Latin square. The results of the analysis of variance showed that glidants have the greatest influence on the fluidity, the bulk density and the bulk density after shrinkage. Neusilin US 2 significantly affects the fluidity of the powder masses and Hausner ratio, the talc having the greatest effect on the bulk density and the bulk density after shrinkage of the powder masses. The representative of the disintegrants group – Sodium starch glycolate most influences the compressibility index, the sugar-based filler – Pearlitol 500 DC – on the angle of repose. Conclusions. The effect of 25 excipients on the pharmaco-technological characteristics of the powdered tablet masses with dry extract of Sanguisorba officinalis was studied. It was found that among the sugars-based fillers equally good results were shown in the powder masses with Compri sugar, Tablettose 80 and Pearlitol 500 DC; among the microcrystalline cellulose based fillers is Prosolv 90; among glidants – Neusilin US 2; no comparison was made of the disintegrants and lubricant excipients from the studied list of leader substances. The results of the studies indicate the possibility of obtaining tablets by the direct compression method, and further study of their pharmaco-technological characteristics will allow to establish the optimal composition of excipients.

Spectrophotometric determination of a substance trifusol in a veterinary suppository

The purpose of the work was to develop of a method for the quantitative determination of piperidinium 2-[5-(2-furyl)-4-phenyl-1,2,4-triazol-3-ylthio] acetate (trifuzol) as part of a dosage form – an effervescent intrauterine suppository using spectrophotometry in the ultraviolet region spectrum and its validation according to State Pharmacopoeia of Ukraine. Materials and methods. The study was used a working standard sample of trifuzol, intrauterine effervescent veterinary suppositories, 1.0 g of trifuzol, as a solvent – purified water. Analytical equipment: Specord 200 spectrophotometer, electronic scales ABT-120-5DM, ultrasonic bath ELMASONICE 60 H, class A measuring dishes. Method of spectrophotometric analysis was used. Results. A spectrophotometric method has been developed and validated for the quantitative determination of trifuzol in a dosage form – an intrauterine effervescent veterinary suppository, based on measuring the absorption of an aqueous solution of the drug at 278 nm. The methodology tally the requirements of State Pharmacopoeia of Ukraine for such validation characteristics as specificity, linearity, precision, correctness, and robustness. The analysis of the predicted total uncertainty of the analysis was showed the reproducibility of the method and the possibility of its application in other laboratories. Conclusions. A method for the quantitative determination of trifuzol in the composition of the dosage form, an effervescent intrauterine suppository, according to the requirements of State Pharmacopoeia of Ukraine, was developed and validated. It was proved that according to such validation characteristics as linearity, specificity, precision, correctness, and robustness, the technique is correct.

Synthesis and structure of salts of 2-(((3-mercapto-5-methyl-4H-1,2,4-triazole-4-yl)imino)methyl)benzoic acid

Modern pharmacy and medicine can offer a substantial number of highly effective synthetic medicines. A great portion of these medicines falls into the group of 1,2,4-triazole derivatives. 1,2,4-Triazoles are distinguished by important pharmacological properties, including antimicrobial, antifungal, anti-inflammatory, hypoglycemic, while also being capable of stimulating the central nervous system. Undoubtedly, a constant increase of number of publications regarding the synthesis, characterization of biological, chemical, and physical properties of 1,2,4-triazole derivatives by both foreign and Ukrainian researchers promotes the search for promising compounds of this class of heterocyclic compounds globally. The purpose of our work was to synthesize and characterize structures of salts of 2-(((3-mercapto-5-methyl-4 H -1,2,4-triazole-4-yl)imino)methyl)benzoic acid, as potentially bioactive compounds. Materials and methods. The physical-chemical characterization of the synthesized compounds was conducted according to the guidelines provided by the State Pharmacopoeia of Ukraine. The melting point was determined using MPA100 apparatus. Elemental analysis was held using Elementar Vario L.cube analyzer. 1 H NMR spectra were recorded using Varian Mercury VX-200 spectrometer (1Н, 200 MHz). Chromatographic and mass-spectrometric data were obtained using Agilent 1260 Infinity LC system coupled with Agilent 6120 mass spectrometer. Results and discussion. 2-(((3-Mercapto-5-methyl-4 H -1,2,4-triazole-4-yl)imino)methyl)benzoic acid was used as the starting compound for the synthesis of the new structures. In order to afford the desired compounds, the starting material was subjected to salt formation reactions with ammonium hydroxide, sodium and potassium hydroxides, methylamine, ethylamine, dimethylamine, 1 -propylamine, 2 -propylamine, monoethanolamine, diethylamine, tert -butylamine, piperidine, piperazine, morpholine, 2-methylpiperidine, and 4-methylmorpholine whether in alcohol or water solutions. Conclusions. The chemical experiments resulted in 16 new substances, salts of 2-(((3-mercapto-5-methyl-4 H -1,2,4-triazole-4-yl)imino)methyl)benzoic acid. The chemical structure of the synthesized compounds was confirmed using instrumental methods, including 1 H NMR spectroscopy, LC-MS, and elemental analysis. The obtained salts will be used in further pharmacological research.

Technological aspects of obtaining liquid extracts of black poplar buds and determining the strategy for their standardization at the pharmaceutical development stage

The aim. Conducting research on the development of technology for obtaining liquid extract of poplar black buds, their standardization and determining the optimal parameters of the technological process of extraction, which should provide the required content of biologically active substances and pharmacological activity of the drug. Methods. The production of liquid extracts was carried out by the method of percolation. The quantitative determination of the amount of hydroxycinnamic acid derivatives was carried out by the unified spectrophotometric method recommended by the State Pharmacopoeia of Ukraine, in terms of coffee acid, at an analytical wavelength of 509 ± 3 nm. To determine the quantitative content of the sum of flavonoids was used the method of differential spectrophotometry, flavonoids were calculated in terms of luteolin, by the reaction of flavonoids with a 2 % solution of aluminium chloride in ethanol (96 %) R at an analytical wavelength of 398 ± 3 nm. Results. The research on the technology of obtaining liquid extracts of black poplar buds was carried out. The technological parameters of the crushed medicinal plant raw material of the black poplar buds (bulk, the coefficient of filling of the dry raw material) were determined and the extraction parameters were calculated. It is established that the process requires the use of 2nd and 3rd discharges, and returns them to the process at the first stage of the process for the series that follows. To increase the absolute content of biologically active substances, it is rational to change the extraction regimes (infusion time, extractant flow rate, temperature). The quantitative determination of extractive substances and spectrophotometric determination of the amount of hydroxycinnamic acid derivatives in terms of coffee acid, as well as the amount of flavonoids in terms of luteolin at all stages of the process of obtaining liquid extracts was done. The influence of the concentration of the extractant on the qualitative composition of the obtained extract was established. The optimal extraction conditions were selected and the technology for ethanol extracts based on ethanol (96 %) R and ethanol (70 %) R was developed from medicinal plant material of black poplar buds. To increase the absolute content of biologically active substances in liquid extracts experimentally argued to increase the infusion time to 24 hours. The liquid extracts of black poplar buds have been developed for their further screening studies. Conclusions. As a result of the study was developed the technology of obtaining liquid extracts of poplar black buds, their standardization was carried out, the optimal parameters of the technological extraction process were determined, ethanol extracts were developed for their further screening studies

Development and Validation of Methods for Identification and Quantification of Biological Active Substances in the Fruit of <i>Tetrapleura tetraptera</i>

This study was conducted to identify the biological active substances (BAS) from the fruit of Tetrapleura tetraptera obtained from Ghana. TLC, UV Spectroscopy and differential spectrophotometry methods of analysis were employed in this study. Identified BAS included flavonoids, polysaccharides and amino acids. Following state pharmacopoeia of Ukraine (SPU) requirements to validate the developed techniques were employed in this study, and the following validation properties specificity, linearity, range, precision accuracy (convergence) and robustness was determined. These characteristics did not exceed the eligibility criteria as stated in (SPU) Appendix 2. Thus the technique can be made to the SPU monograph on fruits of Tetrapleura tetraptera.

Features of standardization and registration of dietary supplements compared to drugs

The constant increase in the number of dietary supplements and the demand for them, as well as the progression of self-medication with the use of over-the-counter medicines, raises questions about their effectiveness, safety and bioequivalence. There are also questions about the criteria for ingredients, production, standardization and registration of finished medicines and dietary supplements.The aim. The aim of the work is to summarize information on the features of standardization, certification and registration of dietary supplements in comparison with drugs in the territory of Ukraine.Materials and methods. Data were collected and analyzed from the current scientific literature and regulatory documents to perform the research.Results. Production, standardization and circulation of finished medicines and dietary supplements is carried out in accordance with the current legislation of Ukraine, international standards (ISO, ICH, GxP) and the requirements of the State Pharmacopoeia of Ukraine. According to these documents, the requirements for the quality of medicines and dietary supplements differ, but unlike ten years ago, today there can be increased regulation and control on the part of the state and law enforcement agencies to eliminate cases of falsification and circulation of unregistered means.The current legislation of Ukraine regulating the production, quality and circulation of finished medicines harmonized with the EU puts forward requirements for providing the population with quality imported / domestic medicines. Regarding dietary supplements, the procedure of harmonization of the legislation of Ukraine with the EU has started, which in the future should lead to improvement of the quality of these remedies and increase of control from the state.Discussion. We generalized requirements for the features of standardization and registration of dietary supplements in the territory of Ukraine, which must be observed in the manufacture, quality control, registration and sale of dietary supplements.Conclusions. Simpler registration, implementation and wider market conditions (multi-level marketing system, Internet) lead to a rapid increase in the production of dietary supplements in Ukraine and their imports. We generalized information about the requirements for the quality of dietary supplements in comparison with finished medicines, and the features of their registration in the territory of Ukraine according to the current legislation

Microscopic research of shoots of the Salix cinerea L. of Ukrainian flora

Representatives of the Salicaceae family are valuable sources of medicinal plant material that has been used in traditional medicine in many countries around the world.. In European countries, some willow species are official plants. It is the bark of willow in many countries called natural aspirin. The decoction of the willow bark is used as an antimalarial, antipyretic, wound healing, antiseptic, hemostatic, astringent and anti-inflammatory agent. Plants of the genus Salix L . have a variety of component composition and contain a complex of biologically active compounds: primarily polyphenolic compounds, phenol glycosides, salicylates, flavonoids, hydroxycoric acids, essential oils, vitamins, carotenoids, polysaccharides. The bark of young branches of different willow species, including Salix purpurea L ., Salix fragilis L ., Salix daphnoides Vill ., have been included in the edition of the European Pharmacopoeia and since 2014 to the State Pharmacopoeia of Ukraine. Expanding the raw material base of medicinal plant raw materials is an urgent problem that can be solved through the introduction into the pharmaceutical practice of systematically close autochthonous and introduced willow species widespread inUkraine. The purpose of this work is the determination of microscopic diagnostic features of the willow goat ( Salix cinerea L .) shoots of Ukrainian flora for the plant material identification. Materials and methods. The object of the study was dry shoots of Salix cinerea L . Vegetable raw materials were collected in May–August 2016–2018 in Kharkiv, Zakarpattia and Kyiv region of Ukraine. The study of the anatomical structure of goat willow shoots was performed using the methods of light and electron microscopy. The ultrastructure of the epidermal leaf tissue surface was further studied using scanning microscopy techniques. Results. An in-depth study of the anatomical structure of the shoots of Salix cinerea L . has been carried out and the main diagnostic macro- and microscopic features of perspective medicinal raw materials have been established. Conclusions. The obtained results significantly expand information on the anatomical structure of shoots of Salix cinerea L . flora of Ukraine and could be used in the standardization of raw materials of species of the family Willow.

Study of structural and mechanical properties of bases in the development of dental gel with combined composition

Aim. The development of the composition of the dental gel for the treatment of infectious and inflammatory diseases of the oral cavity, taking into account the physicochemical properties of the active pharmaceutical ingredients, namely the justification of the type and concentration of the gelling agent and other excipients.Methods. The determination of organoleptic characteristics, uniformity of gel samples, pH of aqueous extract, and structural viscosity index was carried out according to the methods of the State Pharmacopoeia of Ukraine. Rheological studies were carried out using a rotational viscometer of the rotating type BROOKFIELD DV-II + PRO (USA) with a coaxial cylinder system.Results. In order to choose the optimal composition of the gel base, experimental samples with various gelling agents were developed (Carbopol 974P, Carbopol 934P, Carbopol Ultrez 10, xanthan gum, sodium alginate, sodium carmellose) and their organoleptic characteristics, structural viscosity and colloidal stability were studied. The physicochemical and rheological studies that were carried out, allowed us to conclude that it is rational to use the Carbopol Ultrez 10 gel former at a concentration of 1.1 %. When choosing neutralizing agents, sodium hydroxide and trometamol were used in the studies. According to the results of studies, sodium hydroxide at a concentration of 0.32 % was selected as a neutralizer, which provides maximum, stable viscosity in the pH range from 5.0 to 7.0.Concusions. The composition of the basis of a dental gel for the treatment of infectious and inflammatory diseases of the oral cavity has been developed: Carbopol Ultrez 10 - 1.1 %, sodium hydroxide solution 10 %–0.32 %

The microscopical investigation of diagnostic diseases of Thymus х Citriodorus var. «Silver Queen» herbs

The actual problem of modern pharmacy is the study of promising essential oil plant species with pronounced antimicrobial and anti-inflamattory activity for their further introduction in medical practice. Species of one of the most famous Thymus L. genus are characterized by a great diversity and distribution in the world flora. The genus has about 400 species, of which up to 50 are identified in the modern flora of Ukraine. They are widespread in countries of Europe, Minor Asia, Middle Asia, North Africa, and the Mediterranean basin. Phytochemical studies the species of the Thymus L. genus were established the accumulation of various biologically active substances: essential oils, flavonoids, hydroxycinnamic acids, polysaccharides, tannins, fatty oils, vitamins, triterpene saponins, amino acids, bitterness, gums, inorganic elements. Essential oils and herbal extracts are part of phytopreparations with pronounced antimicrobial, anti-inflammatory and antioxidant activity. Ornamental varieties of this species are successfully cultivated in Western Europe and Ukraine: «Silver Queen», «Doone Vally», «Golden Duarf», «Bertram Anderson».
 Lemon thyme (Thymus x citriodorus Pers. Schreb. var. «Silver Queen») is promising for cultivation and introduction into medical practice. The plant has the necessary raw materials and a promising composition of biologically active compounds. The aim of the work is to install the characteristic microscopic diagnostic features of lemon thyme herb (Thymus x citriodorus Pers. Schreb. var. «Silver Queen»), harvested in Ukraine. We carried out a morphological, anatomical and microscopic study of fresh and dried herbal raw materials. The results of the research were obtained with a «Micromed XS-3320» microscope with a digital camera (5 mpix) in combination with a computer and «Biolam» with an FN-6 photo nozzle for direct and reflected light. When conducting morphological, anatomical and microscopic study of herbal raw materials of lemon thyme, common and distinctive features were established. Morphological, anatomical and microscopic studies of lemon thyme herbal raw materials were conducted and common and distinctive features were established. The established distinctive diagnostic features of lemon thyme can be used to identify herbal raw materials and are included in the draft article of the state pharmacopoeia of Ukraine «Herba Thymus x citriodorus Pers. Schreb. var. «Silver Queen».

Study of the morphologo-anatomic signs of shoots of the Salix caprea L. of Ukrainian flora

Representatives of the Salicaceae family are valuable sources of medicinal plant material that has long been used in traditional medicine in many countries around the world. In European countries, some willow species are official plants. The bark of young branches of different willow species, including Salix purpurea L., Salix fragilis L., Salix daphnoides Vill., have been included in the edition of the European Pharmacopoeia and since 2014 to the State Pharmacopoeia of Ukraine. Expanding the raw material base of medicinal plant raw materials is an urgent problem that can be solved through the introduction into the pharmaceutical practice of systematically close autochthonous and introduced willow species widespread in Ukraine.Aim. Determination of macro- and microscopic diagnostic features of the willow goat (Salix caprea L.) shoots growing in Ukraine, for the development of further regulatory documentation for medicinal plant raw materials and the use of standardized raw materials in the design of medicinal products based on willow shoots.Methods of the research. The object of the study were dry shoots of Salix caprea L. Vegetable raw materials were collected in May-August 2016-2018 in Kharkiv, Zakarpattia and Kiev region of Ukraine.Study of the morphological and anatomical structure of goat willow shoots was performed using the methods of light and electron microscopy. The ultrastructure of the epidermal leaf tissue surface was further studied using scanning microscopy techniques.Results of the research. An in-depth study of the morphological and anatomical structure of the shoots of Salix caprea L. has been carried out and the main diagnostic macro- and microscopic features of perspective medicinal raw materials have been established.Conclusions. The obtained results significantly expand information on the anatomical structure of shoots of Salix caprea L. flora of Ukraine and will be used in the standardization of raw materials of species of the family Willow

THE DEVELOPMENT OF THE COMBAINED PHARMACEUTICAL COMPOSITION WITH PLEIOTROPIC ACTIVITY BASED ON ORIGINAL SPERMOMODULATING SUBSTANCE

The article is devoted to the results of the theoretical and experimental investigations on the development of the optimal formulation of the pharmaceutical composition based on Kathiazin and Succinic acid in the solid gelatinous capsules. The glutaminic acid has been introduced into the pharmaceutical composition to improve the bioavailability of the succinic acid. The content of active pharmaceutical substances has been determined. The single dose of Kathiazin is 120 mg, succinic and glutaminic acids — 100 mg. The kind of auxiliary substances used in modern pharmaceutical technology of the solid dosage forms has been grounded according to the literature data. The pharmacotechnological testing of the active pharmaceutical ingredients and auxiliary substances used in our research work has been carried out. The pharmaco-technological properties of the substances investigated according to the articles of State Pharmacopoeia of Ukraine (2 edition) have been estimated. The assessment of obtained data allowed to elaborate the composition of the experimental capsules masses. The flowability, bulk density, angle of repose, compressibility index and Hausner ratio of the mixtures created have been investigated due to requirements of the State Pharmacopoeia of Ukraine. On the base of scientific researching the most perspective pharmaceutical composition with excellent values of the flowability, angle of repose, bulk density, compressibility index and Hausner ratio has been chosen. This composition contains mannitol as the basic excipients for capsules mass. The silicon dioxide colloidal (Aerosil®) is considered to be glidant substance which provides excellent flowability. As the result of the pharmaco-technological researches the qualitative and quantitative composition of the combined capsules based on Kathiazin and succinic acid has been developed. The testing of the pharmaco-technological parameters has proved the composition obtained is suitable to be encapsulated using different types of laboratory and industrial equipment. The elaborated combined dosage form based on Kathiazin and succinic acid may be proposed as a new original medicine with pleiotropic activity for treatment hepatitis of different origin in men with spermatogenesis disturbances.