Drug development & registration最新文献

{"title":"Analysis and Evaluation of Prospects for the Development of New Drugs Derived from Benzodiazepines","authors":"N. Porseva, F. V. Sobin, A. V. Soloninina, N. A. Pulina, E. R. Kurbatov, O. Dvorskaya","doi":"10.33380/2305-2066-2023-12-4(1)-1639","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1639","url":null,"abstract":"Introduction. The use of drugs derived from benzodiazepine for the treatment of various diseases continues to be relevant. Benzodiazepines are approved by most regulatory authorities around the world. Despite the large number of side effects and non-medical use, they are becoming more promising in emergency care for prolonged seizures and epileptic status.Aim. To analyze the existing medicines on the market of the Russian Federation based on benzodiazepine derivatives and assess the prospects for development in this direction.Materials and methods. The study was conducted on the basis of regulatory legal acts in the field of healthcare and the circulation of medicines, publications of Russian and foreign authors, the results of scientific research using situational, comparative, structural-logical and content analysis methods. The information base of the study was the online database \"State Register of Medicines\" (grls.minzdrav.gov.ru), databases of peer-reviewed publications: PubMed and Scopus.Results and discussion. Data were obtained on the range of medicines derived from benzodiazepines according to the following indicators: international nonproprietary names, trade names, medicines, manufacturing countries and enterprises, dosage forms. The problem of \"medicinal sovereignty\" is discussed. Promising niches have been found for the development of innovative drugs derived from benzodiazepines.Conclusion. It has been established that mainly domestic benzodiazepine-type drugs are represented on the Russian pharmaceutical market, while there is a certain shortage of pharmaceutical substances. In Russia, such dosage forms as films, transdermal plasters and preparations for the inhalation use of benzodiazepine derivatives are not registered. It is important to create innovative dosage forms capable of providing a fast, non-invasive and socially acceptable method of use and a high rate of adherence to treatment by patients.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"139 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139165859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Antihypoxic Activity of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic Acids and Their Reaction Products with Substituted Hydrazines","authors":"K. V. Namyatova, S. S. Zykova, D. S. Ovchinnikov, S. Shurov","doi":"10.33380/2305-2066-2023-12-4(1)-1654","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1654","url":null,"abstract":"Introduction. Hypoxia is a violation of oxidative processes in tissues that occur when oxygen is insufficiently supplied to them or when its utilization is disrupted during biological oxidation. Chronic hypoxic damage plays an important role in the occurrence and development of various diseases, which necessitates the synthesis of new compounds with antihypoxic activity.Aim. The purpose of this study is to synthesize and investigate the antihypoxic activity of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids and their reaction products with substituted hydrazines.Materials and methods. 2-Aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids (I–VI) were obtained with high yields as a result of the interaction of 4-aroyl-2,4-dioxobutane acids with 3-amino-5,5-dimethylcyclohex-2-enone. Interaction of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids with benzyl- and (2-phenylethyl)hydrazines 5-aryl-2-benzyl- and 2-(2-phenylethyl)-8,8-dimethyl-3,7,8,9-tetrahydro-2H-pyrido[4,3,2-de]cinnoline-3-ones (VII–XII) were obtained. As a result, 12 compounds were synthesized. The study of the antihypoxic activity of the obtained compounds was carried out in vivo on a model of normobaric hypoxia with hypercapnia.Results and discussion. The synthesized compounds were tested for the presence of antihypoxic action. The most pronounced antihypoxic activity is characteristic of compounds VI and VIII, which have a methoxy group and a methyl radical in the para-position of the phenyl substituent at C5, respectively. The presence of chlorine in the structure of compound III, fluorine in compound X and the absence of substituents (compounds I and VII) contribute to the prohypoxic effect. According to the results of the study, both quinolincarboxylic acids and pyridocinnolines are potential antihypoxants.Conclusion. A comparative analysis of the antihypoxic activity of the synthesized compounds was carried out, the relationship between their structure and severity of action was established, the most active substances were identified.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"22 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139164485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial Activity of New N-substituted Amides of Aroylpyruvic Acids and Their Silver Salts","authors":"V. V. Novikova, V. O. Vasilev, V. L. Gein, O. V. Nazarets, A. V. Romanova, O. V. Bobrovskaya, N. Buzmakova","doi":"10.33380/2305-2066-2023-12-4(1)-1602","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1602","url":null,"abstract":"Introduction. An important direction of modern pharmacy is the production of new domestic substances with anti-infectious activity, within the framework of ensuring the technological sovereignty of the state. Optimization of methods for determining antimicrobial activity is an integral part of these studies. Previously obtained silver salts of pyrazoles and pyrazolecarboxamideshad high antimicrobial activity. This work presents the results of determining the antimicrobial activity of new biologically active compounds synthesized by a salt formation reaction with silver ions at the carboxyl group of aroylpyruvic acid amides containing anthranilic acid in the amide fragment.Aim. Obtaining previously unknown amides of aroylpyruvic acids and their silver salts and studying their antimicrobial activity (AMA).Materials and methods. New N-substituted amides of anthranilic acids and their silver salts were obtained by organic synthesis methods. To study their antimicrobial activity, a micromethod of double serial dilutions was used on screening strains of S. aureus ATCC 6538P, E. coli ATCC 25922, as well as E. faecalis ATCC 29212, S. aureus Wood 46, S. abony No. 103/39 for highly active compounds. Additionally, a method of accounting for the results was carried out using the phenomenon of fluorescence in interaction with rezazurin, indicating the presence of living microbial cells.Results and discussion. The presence of antibacterial activity of silver salts 2a and 2b in relation to the studied strains was established: the minimum suppressive concentration (MPC) of compound 2a is 23.4–31.2 micrograms/ml, 2b is 3.9–5.8 micrograms/ml. When taking into account the results of the study of AMA using the phenomenon of fluorescence, it was found that they either coincide with the values of MPC determined visually, or indicate less antibacterial activity. Comparison of these results and seeding of the contents of the wells on a dense nutrient medium with respect to screening strains indicates that the suppression of fluorescence in experimental wells in the range of 99–82 % compared with the control is accompanied by the absence of bacterial growth (bactericidal effect), with fluorescence inhibition of less than 60 %, a pronounced growth of microorganisms is observed. In the intermediate range, the growth of single colonies is observed (bacteriostatic effect).Conclusion. The results of the study showed that the new silver salts of N-substituted amides of aroylpyruvic acids have high antimicrobial activity. The correspondence of the type of antibacterial activity to the degree of fluorescence inhibition was established.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"83 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139164283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of the Composition and Technology of Capsules Containing Peony Evadiant Rhizomes and Roots Dry extract and Glycine","authors":"E. A. Zamakhaeva, M. M. Smirnova, O. A. Oleshko, M. V. Chirkova","doi":"10.33380/2305-2066-2023-12-4(1)-1610","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4(1)-1610","url":null,"abstract":"Introduction. The development of dosage forms of sedative action is an urgent task of pharmaceutical technology in view of the prevalence of diseases of the nervous system. Peony rhizomes and roots dry extract in combination with glycine have a sedative and anxiolytic effect, which is associated with an improvement in the psycho-emotional state. Taking into account the physicochemical characteristics and composition of biologically active substances of peony rhizomes and dry extract roots, it is necessary to select auxiliary substances that improve its technological properties.Aim. Development of the composition and technology of hard gelatin capsules containing dry peony rhizomes and roots, dry extract and glycine.Materials and methods. Objects of research – dry peony rhizomes and roots (LLC \"Kazan Extract Plant\", Russia), glycine (JSC \"Biokhimik\", Russia). Excipients: apple pectin (LLC TD \"HIMMED\", Russia), starch (LLC TD \"HIMMED\", Russia), aerosil (LLC TD \"HIMMED\", Russia), lactose (LLC TD \"HIMMED\", Russia), microcrystalline cellulose (LLC TD \"HIMMED\", Russia), basic magnesium carbonate (LLC TD \"HIMMED\", Russia), magnesium oxide (LLC TD \"HIMMED\", Russia).Results and discussion. The composition and technology for obtaining capsules containing dry peony rhizomes and roots, dry extract and glycine, have been substantiated. The quality indicators of peony rhizomes and roots of dry extract in combination with glycine and developed capsules were determined.Conclusion. The composition of capsules of peony rhizomes and roots of dry extract and glycine has been developed, auxiliary substances have been selected to ensure satisfactory technological properties of the mass for filling the capsules.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"50 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139164674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of the Tablet Dosage Form Composition for the Inductor of Hepatocytes Monooxygenase System Based on 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine","authors":"A. I. Petrakov, V. V. Sheikin, S. Krivoshchekov, E. Bezverkhniaia, A. M. Guryev, M. V. Belousov","doi":"10.33380/2305-2066-2023-12-4-1517","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1517","url":null,"abstract":"Introduction. Cytochromes P450 depression is the reason for the low effectiveness of etiotropic and pathogenetic therapy of hepatitis. Recent experimental and clinical studies demonstrated the need for use of inducers of hepatocytes monooxygenase system to increase the effectiveness of treatment of chronic hepatitis and cirrhosis. 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine is a promising inducer of hepatocytes monooxygenase system with detoxifying and cytoprotective activity demonstrated in models of acute hypobaric hypoxia, liver ischemia, unconjugated hyperbilirubinemia, toxic hepatitis. Development of a dosage form for 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine requires evaluation of its technological properties which was the aim of the present study.Aim. Preparation of a tablet dosage form for 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine by direct pressing.Materials and methods. The object of the study was the substance of 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine (DPDX270216001 series). Lactose monohydrate (200-559-2, LLC \"Neftegazkhimkomplekt\", Russia), microcrystalline cellulose (100-32-2, Silverline chemicals Ltd., India), potato starch, hydroxypropyl cellulose (ZW180113, Fengchen Group Co., Ltd., Китай), talc (LLC \"Agat-Med\", Russia), magnesium stearate (209-150-3, Ataman Chemicals) were used as excipients. Evaluation of the substance properties was carried according to the following indicators: appearance, loss on drying, fractional composition, flowability, bulk density, porosity, tablet compression (cohesion), ejection force of the tablet from matrix. Tablet masses were evaluated according to the following indicators: flowability, bulk density, tablet compression (cohesion), ejection force of the tablet from matrix. The tablets were obtained by the method of direct pressing. The analysis of obtained tablets were carried out according to the following parameters: average weight, crushing strength, disintegration. The tests were carried out in accordance with the Russian Federation State Pharmacopoeia.Results and discussion. The substance demonstrated poor compression (cohesion), low flowability, low bulk density and high porosity. The addition of lactose monohydrate and microcrystalline cellulose improved the cohesion (compression) parameter, but increased the ejection force of the tablet from matrix. The subsequent addition of magnesium stearate reduced the ejection force of the tablet from matrix by 5 times. The flowability of the tablet mass increased to 3,5–4,0 g/s, the disintegration time of the tablets increased (13–14 min). The introduction of 10 % disintegrators into the mold improved the disintegration rates.Conclusion. Based on the studied properties of the substance, was developed the optimal ratio of tablet mass. The possibility of obtaining a dosage form – tablets of 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanth","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"2018 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139239498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choleotropic Activity of Cistus salviifolius Extract","authors":"E. D. Semivelichenko, A. Ivkina, A. V. Karavaeva, A. Y. Grishina, E. I. Eletskaya, M. Krasnova, K. O. Sidorov, I. A. Titovich, D. Ivkin","doi":"10.33380/2305-2066-2023-12-4-1646","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1646","url":null,"abstract":"Introduction. It is known that a number of species of the genus Cistus are used in Mediterranean folk medicine in the form of infusions and herbal teas to treat digestive problems and acute respiratory virus infection. Empirical data have accumulated that sage incense extract improves the condition of patients with chronic cholestatic liver diseases (CLDs). Currently, only ursodeoxycholic acid (UDCA) is the generally accepted drug for the treatment of most CLDs.Aim. Comparative efficacy evaluation of Cistus salviifolius extract (at 2 doses levels) compared to the reference medicine ursodeoxycholic acid Ursosan® (at a therapeutic dose) in intragastric administration to mice in a cholestasis model induced by intragastric administration of alphanaphthylisothiocyanate (ANIT) oil solution during 20 Days.Materials and methods. The cholestase model was induced by intragastric administration of an alpha-naphthylisothiocyanate oil solution to mice during 20 days. The following biochemical parameters were determined in the serum of experimental animals: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, total cholesterol, bilirubin, triglycerides, albumins. Histological analysis was performed on the liver and gallbladder.Results and discussion. Cistus salviifolius extract at a therapeutic dose of 253 mg/kg and at a dose exceeding the therapeutic dose (506 mg/kg), as well as the reference medicine of Ursodeoxycholic acid Ursosan® at a therapeutic dose of 150 mg/kg reduced the level of aspartate aminotransferase in serum increased after ANIT administration to a level of the control group without pathology. Deviations of other parameters from the control group (alanine aminotransferase, alkaline phosphatase, total protein, total cholesterol, bilirubin, triglycerides, albumins) were statistically insignificant. Histological analysis of the liver and gallbladder demonstrated that the severity of ballooning degeneration and cholecystitis were significantly reduced in groups which was treated by Cistus salviifolius extract at two doses, but not in the group with reference drug. The severity of cholestasis was poorly influenced by Cistus salviifolius extract in contrast to ursodeoxycholic acid, which was more effective for this pathology.Conclusion. The conducted study against the background of reports on the effectiveness of the Cistus salviifolius extract in clinical practice allows to recommend its use as a component of combined therapy of a patient with hepatobiliary pathology and as a pharmacoprevention in healthy people in the presence of risk factors.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139238747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technology Criteria for the Manufacturing of Rebamipide Film-coated Tablets","authors":"G. V. Trusov, B. V. Brovchenko, Z. M. Kozlova, I. Krasnyuk","doi":"10.33380/2305-2066-2023-12-4-1467","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1467","url":null,"abstract":"Introduction. The current growth of the pharmaceutical market and stiff competition require from drug manufacturers make a more detailed and thorough fine-tuning of existing production lines. Direct compression technology is a modern and cost-effective technology for solid dosage form drug manufacturing. Roll-compaction tehnology (dry granulation) can be an alternative approach to optimize the manufacturing of formulations, for which the use of wet granulation or direct compression technologies is not possible due to their physical and chemical properties.Aim. The goal of this work is to investigate the possibility of manufacturing Rebamipide tablets by using direct compression technology and dry granulation technology (roll-compaction), avoiding such complicated and more ex-pensive technology as wet granulation. Also aim of this work is study the impact of production methods on such quality factors as disintegration and dis-solution time.Materials and methods. In this study were used such materials as Rebamipide substance (α-[(4-Chlorobenzoyl)amino]-1,2-dihydro-2-oxo-4-quinolinepropanoic acid) (experimental sample), MCC-102 (J. Rettenmaier & Söhne (JRS), Germany), Starch pregelatinized (Colorcon LTD., England), Kollidone SR (BASF, Germany), Croscarmellose sodium (J. Rettenmaier & Söhne (JRS), Germany), Anhydrous citric acid (Scharlau), Sodium lauryl sulfate (BASF, Germany), Aerosil 200 vv Pharma (Evonik Industries AG, Germany), Sodium stearyl fumarate (J. Rettenmaier & Söhne (JRS), Germany), Calcium stearate (FACI, Italy), Film coating VIVACOAT® PA-1P-000 (J. Rettenmaier & Söhne (JRS), Germany). Also were used such equipment as Y shape blender («AZT FARMA K.B.», Russia), roll compactor LGC100 (Beijing Gylongli Automation Tech. Co., Ltd, China), rotary tablet press PG16G (Beijing Gylongli Automation Tech. Co., Ltd, China), tablet coating system Labcoat™ M (O'Hara Technologies lnc, Canada), ionising air gun Simco Cobra (SimcoIon, Netherlands), flowability tester ERWEKA GT (ERWEKA GmbH, Germany), powder density tester ERWEKA SVM 122 (ERWEKA GmbH, Germany), vibrating sieve CISA RP 200N (CISA Cedaceria Industrial S.L., Spain), tablet hardness, thickness and height tester SOTAX HT 10 (SOTAX AG, Switzerland), dissolution tester DT 626/1000HH (ERWEKA GmbH, Germany) and disintegration tester ZT321 (ERWEKA GmbH, Germany).Results and discussion. In a series of experiments were obtained tablet’s cores and film coated tablets by direct compression and roll-compaction methods. Experimentally it was found, that in tablets with similar formulations roller compaction technology provides slower disintegration and dissolution time, compared to direct compression method. This fact should be taken into account during drug development when planning the rate of release of the active ingredient.Conclusion. As a result of the experiments it was shown a direct correlation between the use of a certain technology and its impact in such quality indicators as disintegration ","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139265651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the α2-adrenergic Agonist Mafedine Effects on White Outbred Mouse Behaviour Following Acute Administration","authors":"N. S. Kurmazov, S. A. Chervonetskiy, V. Prikhodko, Yurii I Sysoev, S. V. Okovityi","doi":"10.33380/2305-2066-2023-12-4-1642","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1642","url":null,"abstract":"Introduction. α2-adrenergic agonists are not only used as antihypertensive and sedative agents, but are also of interest as potential medications for the treatment of neurological disorders. Previous research has shown a compound from this class, 6-oxo-1-phenyl-2-(phenylamino)-1,6-dihydropyrimidine-4-ol (mafedine), to exert strong neuroprotection under experimental conditions. Despite its long record of development, the effects of mafedine on animal behavioural characteristics remain unknown.Aim. This work was aimed at evaluating the effects of mafedine sodium at three doses (1, 10, or 50 mg/kg) on white outbred mouse behavior in three tests: Open Field, Elevated Plus Maze, and Light/Dark Box.Materials and methods. Experiments were carried out on 60 white outbred male mice weighing 20–22 g, randomized into 4 groups (n = 15): 1) control (0,9 % saline); 2) mafedine (1 mg/kg); 3) mafedine (10 mg/kg); 4) mafedine (50 mg/kg). All agents were administered via single intraperitoneal injections 20 min before testing. Animal behavior was assessed using the Open Field, Elevated Plus Maze, and Light/Dark Box tests following conventional protocols with group reassignment between tests and an inter-test time interval of at least 2 days. Statistical analysis was carried out using the Prism 8.0.2 software package.Results and discussion. At 1 or 10 mg/kg, mafedine did not affect animal behaviour in either of the tests. At 50 mg/kg, it produced an anxiolytic effect, as indicated by the decrease in the anxiety index values for the Elevated Plus Maze test as well as the increase in peeking out frequency in the Light/Dark Box test, compared to respective control values.Сonclusion. Mafedine sodium salt at doses between 1 and 50 mg/kg was shown to produce no adverse effect on mouse behaviour, indicating a good safety profile of the compound. The discovered anxiolytic effect of mafedine at the highest dose validates its further research not only as a neuroprotector, but also as an anti-anxiety agent.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"49 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139263303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Geometric Configuration of Diethylaminoethanol Derivative in the Pharmaceutical Development of a Dosage Form Based on It","authors":"Yu. M. Kotsur, K. M. Tserkovnaya, E. V. Flisyuk, I. A. Titovich, K. O. Sidorov, I. Narkevich","doi":"10.33380/2305-2066-2023-12-4-1583","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1583","url":null,"abstract":"Introduction. A comprehensive study of the active pharmaceutical ingredient (API) molecule is one of the defining criteria for pharmaceutical development according to the Quality by Design (QbD) concept and the ICH Q8 framework. The spatial arrangement of atoms in the molecule often has a significant impact on the physicochemical and technological properties of API, and hence on the method of producing dosage form based on it.Aim. To study some properties of substances, geometrical isomers of the molecule, which is a derivative of diethylaminoethanol (DEAE), as well as to compare the selected technologies for the preparation of dosage form.Materials and methods. The objects of the study were two substances, spatial isomers of the molecule, a derivative of DEAE, possessing neuroprotective, antiastenic and antioxidant effects. The study of properties of API and the obtained tablets was carried out in accordance with the requirements of the State Pharmacopoeia of the Russian Federation XIV edition, the Pharmacopoeia of the Eurasian Economic Union, as well as the European Pharmacopoeia 9.0 edition. In this research were used substances that have not expired at the time of the study, as well as authorized for medical use.Results and discussion. The geometrical configuration of the DEAE derivative influences the properties of the API, which has an impact on the stages of pharmaceutical development, especially on the development of the technology and formulation of dosage form. The use of cis-DEAE significantly simplifies the technological process and improves the quality of the resulting drug, and as a consequence, better stability and longer shelf life of dosage form may be achieved.Conclusion. In the course of the study, some properties of cis-DEAE API were studied and compared with similar properties of trans-DEAE. A comparison of tablet preparation technologies based on the two mentioned configurations of the DEAE derivative molecule has been carried out. It was found that the isomers have different technological properties and also differ significantly in moisture adsorption capacity. This property determines the approach to tablet preparation. The technology of tablets based on cis-DEAE appears to be simpler, and dosage form based on it is more stable.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"31 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139266687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Development of Dry Extract Technology from Callus Culture Biomass of Scutellaria baicalensis","authors":"A. Danilova, N. Pivovarova, E. V. Flisyuk","doi":"10.33380/2305-2066-2023-12-4-1637","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1637","url":null,"abstract":"Introduction. Plant biologically active substances (BAS) are valuable for drug development in view of their pharmacological effects and metabolic proximity to the human body. As an example of a useful herbal raw material, the roots of Scutellaria baicalensis, which contain species-specific flavonoids, baicalin and scutellarin, possess the potency of creating antiviral drugs and functional nutrition systems with antioxidant and adaptogenic properties. In order to levelling the existing limitations of using intact plant in pharmaceutical practice, we proposed a nature-saving and ergonomic approach of cultivation of S. baicalensis cells under in vitro conditions. This technology allows to extract active substances of S. baicalensis without causing damage to the environment and contributes to the reduction of the time required to produce the necessary amount of plant material with an increase in the efficiency of production processes.Aim. The development of dry extract technology from S. baicalensis callus biomass.Materials and methods. The object of the study – biomass of S. baicalensis cells obtained from callus culture. Functional characteristics (friability, Hausner’s coefficient, Carr’s index, fractional composition, as well as porosity and hygroscopicity) of S. baicalensis biomass and dry extract on its basis were determined according to the methods of the EAEU Pharmacopoeia. Extraction of plant material was carried out by maceration method with heating in a water bath with reflux condenser. Qualitative and quantitative analysis of BAS in the dry extract was carried out by spectrophotometry and high-performance liquid chromatography. Quality indicators and functional characteristics of the finished product were evaluated in accordance with pharmacopeial requirements.Results and discussion. The functional characteristics of the S. baicalensis biomass were evaluated and the possibility of obtaining a dry extract on its basis was confirmed. We selected parameters of BAS extraction process, established the presence of baicalin in the biomass extract and carried out a comparative evaluation of aglycone profile in the extract based on callus culture and roots of intact plant. The properties of the finished product were evaluated for compliance with regulatory requirements, as well as technological characteristics.Conclusion. The quality indicators of the dry extract of the S. baicalensis biomass satisfy the normative conditions. The technological characteristics of dry extract are suitable for the utilisation as a phytosubstance for the development of medicines of combined type and dietary supplements.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139262498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}