Microbiological examination of aerosols and sprays

Scientific relevance. Medicinal products formulated as aerosols and sprays are increasingly used in clinical practice, which makes the control of their quality, including microbiological testing, a highly topical issue. The current regulatory standards for microbiological testing of medicines provide little information on the quality control of metereddose aerosols. Proper microbiological sampling of these medicinal products can be difficult because of their primary packaging. The specialised analytical procedures set forth in international standards require verification and standardisation before use. Medicinal products in the form of sprays, despite being free from the disadvantages of aerosols, are more susceptible to the risk of microbial contamination.Aim. The study aimed to describe specific aspects of sampling, to analyse the results of microbiological testing of aerosols and sprays, and to study the spectrum of microbial contaminants in these dosage forms.Materials and methods. The authors retrospectively analysed the microbiological quality and sterility data for 181 batches of sprays, aerosols, and other inhalation dosage forms. The data were obtained at the Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of Russia in 2020–2022. The Microbiology Laboratory tested the dosage forms according to the specifications provided by the manufacturers. The analysts used well-established testing procedures outlined in the current pharmacopoeias of the Russian Federation and the Eurasian Economic Union.Results. The microbial counts exceeded the acceptable limits in 2.8% of the batches tested. The authors identified the microbial species that contaminated the medicinal products found to be non-compliant with regulatory requirements. Most of the non-compliant sprays that contained benzalkonium chloride as an antibacterial preservative were contaminated with Burkholderia cepacia complex species.Conclusions. The authors consider it relevant to conduct research aiming at using the findings on potential contaminants to improve microbiological testing procedures for aerosols and sprays

ELIMINATION OF FALSE RESULTS OF MEDICINES MICROBIOLOGICAL TESTING

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

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

Substituted 1H-pyrazolo[3,4-b]pyridine-4- and 1H-pyrazolo[3,4-b]pyridine-6-carboxamides have been synthetized through a Doebner–Ugi multicomponent reaction sequence in a convergent and versatile manner using diversity generation strategies: combination of two multicomponent reactions and conditions-based divergence strategy. The target products contain as pharmacophores pyrazolopyridine and peptidomimetic moieties with four points of diversity introduced from readily available starting materials including scaffold diversity. A small focused compound library of 23 Ugi products was created and screened for antibacterial activity

Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness and Iatrogenic Leukopenia

Leukopenia is an essential part of the clinical course of acute radiation sickness and is a side effect of anti-cancer treatment. In both situations, the main factors which determine the survival are the degree of bone marrow suppression and gastrointestinal tract damage due to the presence of a large pool of fast-dividing cells. Leuko- and neutropenia are main limiting factors which may contribute to chemotherapy failure. Hematopoietic cytokines the part of conventional therapy in this field, but their effects require boosting. That is why the use of means and methods of adsorption therapy is considered promising. Sorption therapy creates a basis for sorption detoxification, a doctrine of curative measures directed to the removal of toxic endogenous or exogenous compounds from body fluids. The most widely used types are the purification of blood or its components (hemosorption), oral administration of sorption materials (enterosorption) and application-sorption therapy of wounds and burns. In this chapter, the results of early and recent research and prospects for the use of carbon adsorption therapy for the treatment of acute radiation sickness and cytostatic myelosuppression are discussed

CORRECTION OF INTERFERON-α-INDUCED DENDRITIC CELL DYSFUNCTIONS IN IMMUNOCOMPROMISED PATIENTS

The correction of impaired functions of in vitro generated interferon-alpha-induced dendritic cells (IFN-DCs) in patients with malignant brain tumors (n = 8), malignant lymphomas (n = 14) and pulmonary tuberculosis (n = 26) was analyzed in the present study. The principal possibility of restoring reduced functional activity of patient DCs was shown. The addition of recombinant human IL-2, complex of pro-inflammatory cytokines, double-stranded human DNA or polyoxidonium to IFN-DC cultures at the stage of maturation could significantly increase the allostimulatory activity of DCs in patients with malignant lymphomas and pulmonary tuberculosis, as well as enhance the cytotoxic activity of cancer patient DCs against NK- and TRAIL-resistant tumor cell line HEp-2. These findings offer new approaches to the correction of DC dysfunctions in the pathology and justify ways of improving the treatment of infectious diseases and cancer using dendritic cell vaccines

INTERLEUKIN-10 REGULATES PD-1-B7-H1-MEDIATED CYTOTOXIC ACTIVITY OF DENDRITIC CELLS

In this investigation the phenotypic and functional properties of healthy donor and patient with pulmonary tuberculosis (PT) dendritic cells (DCs) were characterized. We also studied the influence of IL-10 on the phenotype and apoptosis-inducing activity of healthy donor DCs. 60 patients with pulmonary tuberculosis with different proliferative response to antigens of M. tuberculosis (purified protein derivative, PPD) and 40 healthy donors were enrolled in this study. It was revealed that DCs, generated in vitro from PT patient's blood monocytes with GM-CSF+IFN-α, were characterized by increased B7-H1 expression, up-production of IL-10 and reducing of allostimulatory activity in mixed lymphocyte culture (MLC). The endogenous IL-10 production by DCs was correlated with expression of B7-H1 in the general group of persons. It was revealed that addition of IL-10 to semi-mature DCs of healthy donor results in increasing of B7-H1 expression, diminishing of allostimulatory activity and enlargement of pro-apoptogenic activity of DCs

Антимикробная активность препаратов прополиса при проведении экспертизы качества лекарственных средств

The present article describes the analysis of the results of pharmaceutical expert evaluation of propolis preparations, performed in the laboratory of microbiology of the FSBI «SCEMP» of the Ministry of Health of the Russian Federation for the period of 2006-2014 in terms of «Antimicrobial activity». During the mention period 43 batches of medicinal products were analyzed, a significant part o which were solid domestic drugs (93%). Experimentally determined the effect of individual factors, such as the type of microorganism, the concentration and choice of nutrient medium, on the result of the analysis for this terms.Представлен анализ результатов фармацевтической экспертизы качества препаратов прополиса, проведенной в лаборатории микробиологии ФГБУ «НЦЭСМП» Минздрава России в период 2006-2014 гг. по показателю «Антимикробная активность». За указанный период проанализировано 43 серии лекарственных средств, значительную часть из которых составили препараты отечественного производства (93%). Экспериментально определено влияние отдельных факторов, таких как вид микроорганизма, его концентрация и выбор питательной среды, на результат анализа по данному показателю

Наше стабільне пандемічне майбутнє

This is an introductory text to a collection of papers from the ICSF 2021: Second International Conference on Sustainable Futures: Environmental, Technological, Social, and Economic Matters, which held at Kryvyi Rih National University, Kryvyi Rih, Ukraine, on May 19-21, 2021. It consists of an introduction, conference topics review, and some observations about the event and its future.Це вступний текст до збірника доповідей ICSF 2021: Друга міжнародна конференція з питань сталого майбутнього: екологічні, технологічні, соціальні та економічні питання, яка відбулася у Криворізькому національному університеті, Кривий Ріг, Україна, 19-21 травня 2021 року. Він складається зі вступу, огляду тем конференції та деяких спостережень щодо події та її майбутнього

3-я Міжнародна конференція зі сталого майбутнього: екологічні, технологічні, соціальні та економічні аспекти

This paper represents a preface to the Proceedings of the 3rd International Conference on Sustainable Futures: Environmental, Technological, Social, and Economic Matters (ICSF 2022) held at the Kryvyi Rih, Ukraine, 24–27 May 2022. Background information and the organizational structure of the meeting, program committee, and acknowledgments of the contributions of the many people who made the conference a success are presented.Цей документ є передмовою до збірника матеріалів 3-ї Міжнародної конференції зі сталого майбутнього: екологічні, технологічні, соціальні та економічні питання (ICSF 2022), що відбулася у м. Кривий Ріг, Україна, 24-27 травня 2022 року. Представлена довідкова інформація та організаційна структура зустрічі, програмний комітет, а також висловлено подяку за внесок багатьох людей, які зробили конференцію успішною