The article dwells upon the results of comparative analysis of the Russian national requirements  and EAEU regulations dealing with evaluation of preclinical pharmacological studies. It highlights historical aspects of elaboration of regulatory requirements and scientific and methodological  recommendations for conducting  and evaluating preclinical pharmacological  studies. According to the EAEU Rules of registration and evaluation of medicinal products for human use, the Common  Technical Document has to include information  on primary pharmacodynamics, secondary pharmacodynamics, safety pharmacology  studies, and pharmacodynamic drug interactions, which are subject to evaluation  during examination  of the preclinical  study results. The national guideline on evaluation of medicines does not contain any clear indication of the subject of examination in primary and secondary pharmacodynamic studies, which can make it difficult to prepare a registration dossier in the format of a Common Technical Document. The article formulates basic approaches to expert evaluation of the results of preclinical studies of primary and secondary pharmacodynamics of medicines. It determines the basics of expert evaluation which covers methodological framework of the research, results of the research, characteristics of the safety profile, extrapolation  of preclinical data, characteristics of risk factors and of the predictable clinical safety profile for patients.

The article describes the status of homeopathic medicines standardisation in the leading world pharmacopoeias. It reviews main requirements for raw materials of plant, animal, and mineral origin, which are used in the production of homeopathic medicines. It also considers requirements for homeopathic pharmaceutical substances, including technologies of obtaining homeopathic mother tinctures, homeopathic dilutions, triturations, etc., mono- and multi-component homeopathic medicines, as well as quality control of homeopathic substances and homeopathic medicines. The article analyses the nomenclature of homeopathic raw materials and homeopathic substances used by the leading world pharmacopoeias. It dwells upon the results of work devoted to the development of requirements for the following homeopathic dosage forms: homeopathic granules, homeopathic eye drops, homeopathic ointments, homeopathic infusions and decoctions,  homeopathic mother tinctures,  homeopathic solutions for injection,  homeopathic solutions and liquid dilutions,  homeopathic syrups, homeopathic mixtures,  homeopathic suppositories, homeopathic tablets, homeopathic triturations.  The article illustrates significant potential of using vibrational spectroscopy and Raman spectroscopy for the detection of distinctive features of homeopathic medicines at ultra-high dilutions. The article presents methodology for structuring pharmacopoeial standards for raw materials used in the production of pharmaceutical substances, for pharmaceutical substances that are used in homeopathic medicines, and for dosage forms, including specific aspects of production and standardisation of homeopathic medicines, which was implemented during preparation of draft monographs for the State Pharmacopoeia of the Russian Federation.

The Government of the Russian Federation approved the State strategy of combating the spread of HIV aimed at prevention of HIV epidemic. One of the goals of the Strategy is to increase the coverage of antiretroviral therapy for people infected with HIV, which includes extensive use of generic drugs. In order for a generic drug to be authorised, the applicant has to submit a report on the results of the bioequivalence studies in which the generic product was compared to the reference product. Atazanavir is an antiretroviral drug, which is also the drug of choice for the treatment and prevention of mother-to-child transmission of HIV. The aim of this study was to analyze the protocols and reports of atazanavir products bioequivalence studies, which were submitted for expert examination  to the FSBI “SCEEMP” of the Ministry of Health of the Russian Federation, and to prepare recommendations  for planning of bioequivalence studies of atazanavir products. The analysis of a number of studies revealed significant differences in the study design and number of subjects. The main reason for these differences is the conflicting data on the intrasubject coefficient of variation of atazanavir, which means that atazanavir may be considered a highly variable drug. The analysis helped to formulate  recommendations for the design of bioequivalence  studies of atazanavir products,  including studies of the maximum dose, studies under fed conditions, and consideration  of atazanavir variation when planning the study design.

X-ray powder diffraction is one of the methods used for detection and analysis of polymorphic forms of pharmaceutical substances. The article elucidates the concept of polymorphism, briefly explains physical characteristics of this phenomenon, conditions of polymorphic transformations and the prevalence of polymorphic forms among drug substances. It should be noted that polymorphism is observed in drug substances belonging to different pharmacologic  classes. Polymorphic  forms of the same drug substance have different solubility, melting point,  resistance to oxidation and to other destructive processes, and, consequently, different surface properties which affect both the rate of absorption of the drug substances and their stability as components of dosage forms. This calls for the need to control the quality of drug substances for potential presence of polymorphic forms. The use of diffraction methods for examination of cryomodified forms of various biologically active compounds obtained by evaporation and subsequent precipitation at low temperatures resulted in obtaining polycrystalline substances with new properties. The article provides results of examination of crystalline modifications of phenazepam  in the form of α- and β-polymorphs, tilorone, fabomotizole, zolendronic acid and dehydroepiandrosterone. It was demonstrated that the use of X-ray diffraction analysis for examination and quality control of polymorphic forms of drugs is a necessary component of identification testing.

The article summarises the results of studies of hydrophilic  interaction  liquid chromatography performed  from 2013 until 2017. The analysis of results obtained  during separation  of a number  of model mixtures of compounds  having different nature  helped to compare  the characteristics  of columns  packed with amino,  amide and nitrile sorbents. It was demonstrated that columns packed with amino sorbents could be used for the analysis of both hydrophilic compounds  and some hydrophobic compounds  containing acidic (4-hydroxybenzoic acid) and potentially acidic groups (nitro groups of nitro compounds;  phenolic hydroxyl groups of butylhydroxyanisole isomers and parabens). It was discovered that chromatographic columns packed with nitrile and amide sorbents have common properties and can be used for the analysis of hydrophilic compounds (hydroxycarbamide) and platinum coordination compounds, but cannot be used for the analysis of butylhydroxyanisole isomers, esters of p-hydroxybenzoic acid and nitrate  esters of isosorbide. The article offers hypotheses about possible mechanisms  of interaction  between test substances and sorbents. It was concluded  that the increase in the acetonitrile  content  in mobile phases, which increases the retention time of the test substances and results in better resolution between their peaks, illustrates the mechanism  of hydrophilic interaction  liquid chromatography.

The article provides the results of a comparative analysis of requirements laid out in the State Pharmacopoeia of the USSR, XI ed. (SPh XI) and the State Pharmacopoeia of the Russian Federation, XIII ed. (SPh XIII) concerning  quality evaluation and standardization of herbal substances, herbal medicines and other herbal products. The article discusses requirements  for the criteria of herbal substances and herbal medicines quality control described in general chapters and monographs that were previously in force and that have recently been adopted. The article mentions new herbal substances that were included into the State Pharmacopoeia of the Russian Federation for the first time as well as herbal substances included into the State Pharmacopoeia of the USSR, X ed., not included into SPh XI, but included into SPh XIII. The article analyses the requirements described in the new general chapters that were recently included into SPh XIII: “Herbal substances. Herbal preparations”, “Determination of heavy metals and arsenic content in herbal substances and herbal medicinal  products”, “Determination of water absorption  factor for herbal substances”,  “Buds”, “Cut-pressed granules”. The article suggests ways to improve methods of analysis of herbal substances and herbal medicinal products in view of recent advances in pharmacopoeial analysis and the increasing requirements for its quality.

Timely diagnosis and efficacious pharmacotherapy of depressive disorders are of immediate concern to the medical practice. The quantitative pharmaco-electroencephalography method enables differential evaluation of the affective disorder treatment efficacy. The aim of the study was to perform comparative evaluation of pharmacological  activity of two treatment regimens for moderate somatization disorders in patients with gastrointestinal pathology: monotherapy with fluoxetine — an antidepressant  of the selective serotonin  reuptake  inhibitors  class, and combination  therapy  with melatonin-containing medicine.  Methods: the severity of the depressive disorder and the efficacy of the treatment regimens were assessed using the Hamilton Depression Rating Scale (HDRS-17). The quantitative  pharmaco-electroencephalography (pharmaco-EEG) was used both before and during the treatment to analyse the effect of the medicinal products on the functional state of the brain in the patients with depressive disorder. Results: it was shown that the combination  of fluoxetine and melatonin  results in a more rapid regression of depressive symptoms according to the HDRS-17 scale. The quantitative pharmaco-EEG method helped to reveal specific differences between the effect of fluoxetin as monotherapy and in combination  with melatonin  on the bioelectrical activity on the patients brain. Conclusions: the analysis of the relative power of the patient brain rhythms by pharmaco-EEG demonstrated a more rapid restoration  of normal EEG rhythms in the patients who received the combination  of fluoxetine and melatonin, than in those patients who received fluoxetine monotherapy which did not result in complete remission of the existing depressive episode in a number of patients after the 42-day treatment course.

The validity of medicines microbial quality testing relies on the adequacy of the test procedure employed. The aim of the study was to analyse factors triggering false results during microbial quality testing of non-sterile  medicinal products, as well as to find ways of their elimination.  Materials and methods: the study was focused on non-sterile  medicinal products tested for microbial quality: N-methylglucamine, L-Malic  acid, Xeroform, Fingolimod hydrochloride, Succinic  acid, Streptocide,  Aripiprazole, Doxazosin, Clopidogrel,  Moxonidine, Tilorone,  Mycophenolic acid, Folic acid, Gabapentin, Dutasteride, Imatinib,  Temozolomide. The study involved the use of the following test strains: Bacillus subtilis, Bacillus cereus, Candida albicans, Escherichia coli, Aspergillus brasiliensis, as well as of reagents and growth media. The methods  used were determination of antimicrobial  activity under conditions of microbial quality testing, and modified in-depth  testing of microbial quality of medicinal products according to the requirements of the State Pharmacopoeia of the Russian Federation, 13th edition. Results: the analysis of literature sources helped reveal the main factors causing false results of microbiological  testing and determine  ways of their elimination.  The article sets forth the results of experimental comparison of two ways of sample preparation  for solid formulations: the standard one described in the State Pharmacopoeia of the Russian Federation, 13th edition, and the one involving the use of a laboratory shaker. The article provides experimental data on specific aspects of elimination of antimicrobial activity against B. subtilis and B. cereus and the use of specific inactivators for particular medicinal products. Conclusions: a set of measures aimed at prevention of false-positive and false-negative testing results should include: sterility control of the growth media and reagents used, monitoring  of facilities; control of growth promotion  properties and selectivity of the growth media; selection of adequate incubation  conditions  and inoculation procedure with due regard to the dosage form; justification of the amount of sample, diluents and dilution factor used; consideration  of the antimicrobial activity of a medicinal product.

The need for identification  testing of active substances or excipients in multi-component medicinal products,  including the use of qualitative tests, calls for research substantiating the choice of tests and test conditions  with due regard to interference  effects caused by other components  of medicinal products and the amount of the sample used. The aim of the study was to develop a methodological approach to designing experiments while selecting qualitative reactions for identification testing of a medicinal product component based on the results of studies investigating the possibility of using known qualitative tests (as illustrated by ascorbic acid in a multi-component product — 0.4 mg of ascorbic acid per 100 mg of the vial contents)  with due regard to interference on the part of other medicinal product components and the amount of the sample used. Material and methods: the study focused on a multi-component medicinal product — lyophilisate for solution for intravenous and intramuscular  injections containing an antiinflammatory active substance and ascorbic acid as a stabilizing agent (antioxidant). The analysis of literature sources helped to determine qualitative tests that were assessed for potential use for identification testing of ascorbic acid as a component of the analysed medicinal product. The study involved experimental testing of the qualitative reactions based on acidic and reducing properties of ascorbic acid. Results: it was demonstrated that several well-known qualitative tests could be used for identification  testing of ascorbic acid as a component of the analysed medicinal product,  namely, the reaction of ferrous ascorbate formation  and the reaction of silver nitrate reduction to metallic silver after preliminary separation of ascorbic acid from the other medicinal product components, as well as the reaction of Prussian blue formation,  iodine test and reaction with a potassium permanganate solution, which do not require additional sample preparation.  It is not practicable to use the reaction with a methylene blue solution and the Fehling’s reagent reaction for this particular medicinal product,  since their results are feeble. Conclusions: the analysis of the multi-component medicinal product helped to develop a methodological  approach to choosing qualitative reactions for identification testing of one of the medicinal product’s components  (e.g., ascorbic acid). The suggested algorithm includes the choice of reactions, determination of their sensitivity and applicability for a particular medicinal product, analysis of the other components’ effects on the results of the chemical reaction,  and the need for additional sample preparation.  The whole complex of the studies performed helped to determine qualitative reactions and optimal conditions for identification testing of the analysed substance.