The aim of the work. Theoretical and experimental substantiation of a rational technology for obtaining a preparation in the form of capsules based on uridine-5-monophosphate of disodium salt, cytidine-5-monophosphate of disodium salt, vitamin B6, thioctic acid and magnesium lactate dihydrate, determination of process parameters that can affect critical quality characteristics active pharmaceutical ingredients in the product and establishing acceptance criteria for each critical process parameter to be used in batch production and process control. Materials and methods. Objects of the research: masses for encapsulation, granulates and the finished product - capsules with the conventional name “Neuronucleos”. To obtain capsules, active pharmaceutical ingredients (API) were used: uridine-5-monophosphate disodium salt and cytidine-5-monophosphate disodium salt (Shanghai Oripharm Co. Ltd., China), thioctic acid (Shanghai Modern Pharmaceutical Co., Ltd..”, China), pyridoxine hydrochloride (“DSM Nutritional Products GmbH”, Germany), magnesium lactate (“Moes Cantabra S.L.”, Spain). The quality indicators were studied: description, average mass of content and uniformity of mass, uniformity of dosage units, dissolution, accompanying impurities, quantitative content of API. Methods of liquid chromatography and complexometric titration were used. Results. It has been established that the use of the direct mixing method does not allow obtaining a mass for encapsulation corresponding to the indicator "Bulk density". The use of the wet granulation method in a fluidized bed has been substantiated. It has been shown that it is difficult to perform granulation in a fluidized bed of an API mixture containing thioctic acid. It has been established that it is rational to obtain a mass for encapsulation in two stages: obtaining a granulate from magnesium lactate dihydrate and pyridoxine hydrochloride with a moisturizer solution (sorbitol + uridine-5-monophosphate disodium salt + cytidine-5-monophosphate disodium salt) and then obtaining a mass for encapsulation from granulate, thioctic acid, anhydrous colloidal silicon dioxide and magnesium stearate by the direct mixing method. Conclusions. On the basis of the performed technological research and analysis of the quality of the obtained capsules, a method for obtaining a capsule mass using the method of wet granulation in a fluidized bed was chosen. The granulation mode was substantiated and the optimal parameters for obtaining a high-quality product were selected, the acceptance criteria for each critical parameter of the technological process were established

Aim. To determine the potential risk factors associated with the critical quality indicators of the combined medicine “Neuronucleos” in the capsule dosage form for the treatment of polyneuropathies using the general risk assessment methodology while planning the drug quality at the stage of pharmaceutical development (PD). Materials and methods. The series of the combined medicine “Neuronucleos” in the capsule dosage form, critical indicators of the drug quality, the flowchart of the drug production, critical control points of the drug manufacturing process were developed. The method of causality was used. The quantitative assessment of risk factors was carriedout using the FMECA methodology. Results and discussion. The main objective of this study was to apply the Quality-by-Design (QbD) approach to PD of the combined medicine in the capsule dosage form based on uridine-5 monophosphate disodium salt (UMP), cytidine-5-monophosphate disodium salt (CMF), vitamin B6, thioctic acid and magnesium lactate dihydrate. For better patient compliance and the product quality, a target quality profile as a base for PD planning, as well as critical quality attributes (CQA) related to the product safety and efficacy were determined. The criticality of each CQA was assessed using a special scale. It was shown that “Quantitative content”, “Uniformity of dosage units”, “Dissolution”, “Impurities” were defined as the most CQA due to the minimum amount of UMF and CMF in the capsule and the possibility of their decomposition and increase in the quantity of impurities. The critical attributes of materials (CMA) were identified, and the characteristics required to control them were determined in order to ensure the expected product quality. The primary assessment of the quality indicator risks of the active ingredients was performed. It was found that the particle size affected the homogeneity, the quantitative content of API and dissolution in FPP, and it was shown that the solubility of active substances had a high risk when performing the “Dissolution” test. To determine the potential factors with a significant impact on the drug quality the maximum number of factors was found, and the Ishikawa diagram was constructed. The risk factors associated with the quality and compatibility of active substances and excipients, the quality of primary packaging, production conditions, the drug quality control and the technological process were identified. These factors are the causes of risk and can lead to a situation with negative consequences for the quality of a medicinal product. The FMECA process assessment allowed us to determine the impact of the manufacturing process on the CQA. Conclusions. At the stage of PD for the combined medicine in the capsule dosage form the potential critical indicators of the drug quality have been determined. The critical parameters of the quality of the initial components and the properties of the product have been assessed; the most probable risks for the drug quality have been identified, analyzed and assessed. Further research is advisable to focus on studying the effect of process parameters on critical parameters of the product quality and assessing risks for quality and creating a validation plan and its implementation.

The aim. The study encompassed some aspects related to perfumes use, which can potentially influence the individual perfume choice, in particular, among different age groups of the Ukrainian population. Factors related to perfumes choice, the state of awareness of respondents regarding quality, safety, and existing stereotypes regarding the characteristics of perfumes and potential harmful effects on the human body were investigated. Materials and methods. The analysis was performed on a sample of 124 residents of Ukraine. Respondents, who were randomly selected, were offered a questionnaire, developed by us, which included 15 items on the demographic characteristics of the subjects and questions related to the perfume use of and stereotypes about them. The Pearson chi-squared (χ2) test was used to analyze the relationships between qualitative characteristics. Results and discussion. About 98 % of surveyed persons in Ukraine use perfumery. Associations were found between age and the probability of purchase by the study participants of non-original perfume products and awareness of the safety of various perfume products. It has been established, that the determining factors when choosing a perfume is a certain scent, while the brand is given secondary importance. An increase in the effect of the brand in older age groups of the population has been demonstrated. Behavioral features of perfume use have been established: in younger women, it is associated with increased self-esteem and the influence of social networks, with age, the focus shifts to the desire for a positive effect on the mood from the use of a certain fragrance. However, in all age groups, the main purpose of perfume using was to improve the emotional state. Middle-aged women are more democratic in choosing perfumery with a specific gender orientation. Conclusions. For the first time in Ukraine, a pilot study was conducted to find possible associations between some biological, behavioral and demographic characteristics and the perfume use. Such factors as age and education level are promising for further analysis of the selected issues

АнАліз фАкторів ризику зАбруднення мехАнічними включеннями лАборАторних серій препАрАту «ніАвіт, розчин для ін'єкцій» нА етАпі фАрмАцевтичної розробки Мета. Вивчення за допомогою діаграми Ішикави одного з інструментів управління ризиками, потенційних факторів ризику на етапі фармацевтичної розробки (ФР), що впливають на якість ін'єкційного лікарського препарату (ЛП) Ніавіт за показником «Механічні включення» (МВ), та подальшого використання цієї інформації для оцінки ризиків ЛП для ін'єкцій. Методи. У роботі застосовано методику причинно-наслідкового аналізу. Для виявлення потенційних факторів, що чинять найбільш значний вплив на якість ЛП «Ніавіт, розчин для ін'єкцій» за показником МВ, побудовано діаграму Ішикави -графічне зображення причин та наслідків. Для контролю видимих і невидимих МВ у препараті для ін'єкцій використовувалися методи контролю згідно з ДФУ. Результати. Проведення аналізу дозволило систематизувати можливі фактори ризику, які впливають на якість лабораторних серій ЛП «Ніавіт, розчин для ін'єкцій» за показником МВ і можуть призвести до негативних наслідків. Висновки. На етапі ФР визначені можливі ризики, пов'язані з критичним показником якості «МВ» препарату «Ніавіт, розчин для ін'єкцій в ампулах по 2 мл». Контроль лабораторних серій препарату, виготовлених з урахуванням усіх можливих ризиків, за показником МВ підтвердив їх відповідність вимогам ДФУ. Ключові слова: механічні включення; оцінка ризиків; діаграма Ішикави; контроль; частинки; розчин для ін'єкцій; Ніавіт

Pyrimidine nucleotides, namely uridine monophosphate and cytidine monophosphate, play an important role in the cellular metabolism of nerve fibers. The combination of these nucleotides with pyridoxine hydrochloride (vitamin В6) in one dosage form will allow us to fully implement the strategy of the complex neurotropic pharmacotherapy in neuropathies of various origins. To develop a stable solution, an important step at the stage of the composition development is to study the compatibility of active substances (active pharmaceutical ingredients - APIs) in solution. Samples of binary solutions and solutions containing all active substances were prepared and examined. The API interaction was determined by various parameters – changes in color, transparency, рН, the total impurity content, etc. Based on a comprehensive study of the processes of the API dissolution the optimal pH limits of the solution required for the stable existence of a combination of substances with different pH values of the medium have been substantiated and experimentally confirmed. As a result of the research, the optimal pH value of the solution recommended is 4.0-4.8. In the composition of substances the amount of water can be in an adsorbed or crystallized, or combined form. This fact should be taken into account in order to correctly calculate the actual amounts of initial ingredients when preparing the solution. The nature of the water component of APIs was clarified when studying the phase composition of samples on a powder diffractometer. The studies conducted have allowed us to determine the directions of further research for developing the composition of an injection drug. This research is in choosing the optimal buffer system and excipients-antioxidants.