Methodological aspects of creating a soft dosage form with the antiviral effect

Aim. Substantiate the methodology of creating the soft dosage form for the treatment of herpes viral diseases, taking into account the existing requirements for pharmaceutical drug development. Materials and methods. Drug creating is possible only with a theoretically and experimentally justified process of planning experimental research. To ensure the effectiveness and minimize side effects of the drug under development, it is necessary to take into account all pharmaceutical factors that have affect on the quality of the drug. These are the nature and quantity of the base, physical and chemical properties of active and auxiliary substances, structural and mechanical characteristics and equipment. The methodological concept of antiviral drug development is based on the implementation of complexes of marketing, pharmaco-technological, physico-chemical and biopharmaceutical research, which ensures compliance of the drug with medical and biological requirements. Results. It was found that the general algorithm of the methodological approach consists of 3 consecutive stages: information retrieval, research and standardization-pharmacological. Based on the analysis of literature sources and own research, a plan for creating of the soft dosage form with the antiviral effect based on acyclovir and miramistin was developed. Conclusions. The main methodological aspects of creating the soft dosage form with antiherpetic action, taking into account the requirements for the quality of the drug are shown. Key words: methodology; drug; research algorithm; soft dosage form

Study of consumer awareness of contraceptives selecting in the family planning process

The work aim is to study the degree of awareness of female consumers about the range of contraceptives and their use, as well as the process of providing contraceptives with the subsequent use of the results obtained to improve the contraceptives supply system for the right strategic marketing decision-making. During the study methods of searching, analyzing, generalizing data from information sources, systemic, comparative, marketing analysis, and survey were used. Results. Before the survey, the modern assortment of contraceptives study and an information array of them was formed, which was used to conduct conjoint analysis. At the same time, a survey among female respondents regarding their awareness of contraception issues was conducted. As a result of the survey, 420 questionnaires with full valid answers of women aged 16 to 49 years were collected. Each of the groups covered a 4-year age interval. In addition, 117 refusals of women to participate in the survey were collected. The reasons of refusals were also taken into account in the study for a broader understanding of the functioning problems of a modern contraceptives supply system. Conclusions. It was found that the degree to which women are familiar with the modern arsenal of contraceptives varies depending on their age. Overall, 78% of women are partially familiar with the entire range of contraceptives. The percentage of women who had a deficit of information about the range of contraceptives increases with the transition to older age groups: after the age of 30, every sixth woman in Ukraine does not know about the existence of some types of contraception. Among women who were familiar with the entire range, the age group of 25-29 years prevails, which is associated with active family planning processes in this age range - 6.42%. Women's views on the process of providing contraceptives and men's role in this process were analyzed. Thus, of the total number of respondents, 117 (21.78%) women refused to take part in the survey, explaining their refusal by their lack of interest in this topic, ignoring the use of contraceptives, or by their shyness. This "taboo" of the topic is closely related to the problems of sex education, problems of motivation and involvement of medical representatives in the dissemination of information about contraceptives and their importance in the process of family planning. In addition, 69% of women prefer to coordinate the choice of contraceptives with their husbands, and only 20% of female consumers, believe that the process of preventing or planning a pregnancy is personally a woman's business. The results of the survey prove the need to intensify health education work to improve the level of education of women and men on contraception, as well as expanding the boundaries of access to contraceptives for the target consumer. Keywords: contraception; consumers; pharmaceutical support

Analysis of the Ukrainian pharmaceutical retail market regarding dorsalgia treatment drugs

Pharmaceutical care for treating dorsalgia is not only of medical significance, but also has a socio-economic aspect. Back pain often occurs in the working-age population. The dorsalgia treatment requires substantial economic costs and leads to deterioration in the quality of life. Aim. To analyze and systematize the official sources concerning medicines for treating dorsalgia at the domestic pharmaceutical market, as well as to determine promising directions for expanding the drug assortment. Results. The results of the study have shown that the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) occupy a leading position by the volume of consumption. In Ukraine, 36 trade names (TN) of medicines with the active substance Paracetamol were registered (re-registered), including 45 % registered drugs under the brand name. The ratio of domestic and foreign NSAIDs is 56 % to 44 %; the proportion of oral dosage forms constitutes almost 50 % of the assortment. The majority of foreign medicines registered in Ukraine are manufactured in European countries, which makes up 38.9 % of the total imports of medicines. France and Great Britain occupy the leading positions in terms of supply with six THs each. The total number of drugs for external use for joint and muscle pain is 131 TH. The macro-contour of the segment of herbal medicines for treating dorsalgia at the pharmaceutical market has been formed. According to the ATX classification, the drugs studied are mostly of the pharmacotherapeutic group M02AX – Other topical products for joint and muscular pain; they are produced mainly by domestic manufacturers (60 %). More than 30 % of them are supplied by the pharmaceutical enterprise Pharmaceutical Factory Ltd. (Zhytomyr). Multi-component medicinal products of plant origin prevail significantly (66.7 %); ointments represent the broadest range (60 %). Conclusions. The limited range of drugs based on plant substances has been found; it contributes to the search for promising plant objects and the creation of new drugs based on them for the local treatment of dorsalgia. Key words: dorsalgia; medicines; herbal medicinal products; pharmaceutical market

The risk-oriented approach to the development and implementation of the pharmaceutical quality system in the production of in-bulk finished products

Aim. To determine the areas of the risk-based approach to the development and implementation of the pharmaceutical quality system with the emphasis on the production of in-bulk finished products, identify the main factors affecting the stability of the functional characteristics of drugs in order to provide their compliance with the international quality standards, Good Manufacturing Practice and quality risk management. Results. 29 pharmaceutical companies with the license in Ukraine for dispensing and packing of medicines from in-bulk products have been identified. The control strategy for the production of medicines for in-bulk products has been developed as a set of measures covering the incoming control of in-bulk products, the primary, secondary packing and their labeling, patient information leaflets, finished drug at release and shelf life, control of operating conditions of premises and equipment, parameters of dispensing and packing stages. The analysis of the specificity of the production of finished drugs from in-bulk products has been performed, and the areas of the risk-oriented approach have been determined to the development and implementation of the pharmaceutical quality system in this type of production based on the risk assessment of significant factors affecting the pharmaceutical production and the use of the appropriate risk management methods for quality in the production of medicines from in-bulk products. Conclusions. It has been determined that the risk-oriented approach to the development and implementation of the pharmaceutical quality system in the production of medicines from in-bulk products is a strategic direction. It allows increasing the effectiveness of the quality management system at a qualitatively new level, achieving goals in order to prevent adverse effects on quality and safety, and it means the best possible customer satisfaction. In our research, the quality guarantees that the pharmaceutical quality system should provide in the production of medicines from in-bulk products have been identified, and the control strategy has been developed. Key words: in-bulk products; medicines; drug quality; risk-based approach; pharmaceutical quality system; Good Manufacturing Practice; quality risk assessment

The study on the development of the technology of the Sedum maximum juice as a biogenic stimulator for obtaining medicines

Due to the complex of biologically active substances (BAS) in the native state, juices are becoming increasingly popular in pharmacy and medicine. We were interested in the Sedum maximum plant as a powerful biogenic stimulant. Despite its wide distribution in the world and in Ukraine, plants of the Sedum L. genus are rarely used. The aim of the study is to determine the technological parameters of the process of obtaining juice from Sedum maximum for the development of technology for its production in pharmacy and industrial conditions and further use in pharmacy and medicine. Results. The optimal method of obtaining fresh juice from Sedum maximum grass using a number of technological techniques in the following sequence was substantiated: fermentation of Sedum maximum grass (keeping in a dark cool place (5 ± 3 ºC) for 5 days; pre-treatment of Sedum maximum grass raw material with boiling water; keeping the crushed raw material at a temperature of 5 ± 3 ºC during the day, purification of unclarified juice with rapid heating to 75-78 °C for 30 min followed by rapid cooling and treatment with 95 % ethanol, sedimentation of Sedum maximum grass juice at a temperature of 5 ± 3 ºC followed by stabilization of clarified juice of Sedum maximum grass with ethanol 15% and chloroethane in the amount of 0.5 %. Conclusions. The quality criteria of the obtained Sedum maximum juice were determined: appearance, pH, dry residue, identification by color reactions and quantitative determination by spectrophotometry (sum of tannins, in terms of pyrogalol). Key words: juice; Sedum maximum; technology; biogenic stimulant

The quality assurance of the medicinal composition using the “Antimicrobial activity” indicator

The aim of the work is to determine the spectrum and strenght of antimicrobial activity of the studied compositions, to compare them with the activity of substancesand to select the most optimal concentration for further combination with each other. Topicality. Nowadays, one of the most common skin diseases is acne and demodicosis, the manifestations of which can be mild (comedones in seborrheic areas), more noticeable (papules-pustular rash) and severe (large cyanotic infiltrative elements in the back, prone to abscessing and scarring). The prevalence of acne and demodicosis currently reaches 90%. With these skin pathologies, it is desirable to use safe and effective drugs for external therapy, which provide rapid improvement of the skin (reduction of inflammation without side effects) to obtain a rapid and high-quality therapeutic effect. In the course of our research, we selected 3 active pharmaceutical ingredients (APIs): metronidazole, benzyl benzoate and benzoyl peroxide - according to the purpose of ICD-10 and their effectiveness in these pathologies. Mild medicines have an advantage over dermatological diseases such as acne and demodicosis because the use of soft medicines is local, namely a targeted effect on the microbial microflora. At present for production of soft medicines for local application such substances as macromolecular compounds are widely used, plasticizers, surfactants,etc. When creating a drug composition, a study was conducted aimed at obtaining soft medicines with certain consumer properties, in particular physicochemical (pH, osmotic activity, homogeneity,etc.) , physical and mechanical properties (rheological parameters). Materials for the study – soft medicines based on cetyl alcohol, Emulgade Sucro Plus, Polyvinylpyrrolidone, Carboxymethylcellulose, Tween 80, Triethanolamine, Propylene glycol, vaseline oil, which as (API) contains metronidazole, benzoyl peroxide, benzylbenzene. The specific antimicrobial activity of the samples was tested in accordance with Order № 167 of the Ministry of Health of Ukraine dated 05.04.2007 by the standard macromethod of serial dilutions in liquid nutrient medium and by the method of diffusion into agar. The minimum inhibitory concentration (MIC) of API (substrates) was determined. Results. The studied compositions of soft medicines and substrates revealed to presence of antibacterial (bacteriostatic) action against the test strains of microorganisms. Conclusions. The test of the compositions of soft medicines and the substance revealed the presence of a slight antibacterial (bacteriostatic) effect against the test strains of microorganisms. Key words: antimicrobial activity; active pharmaceutical ingredients (API); excipients; soft dosage form

Aspects of the implementation of economic models for health technology assessment in clinical trials of medicines

The aim of the work is to scientifically substantiate the basic aspects of developing a methodology for including сost-effectiveness analysis in key processes of clinical trials of medicines. Results. It is established that Ukrainian regulatory system and methodological support of clinical trials with included сost-effectiveness analysis is based on separate regulations in the field of clinical trial and health technology assessment. At the same time, there is no methodological support for the management of сost-effectiveness analysis alongside clinical trials, which would take into account the peculiarities of planning, organizing and conducting such studies. The algorithm of substantiation, development and inclusion of basic components of the analysis of economic effectiveness in the basic processes of planning and the organization of clinical trial of medicines is offered. Emphasis is placed on the need for a proper strategy for analyzing the economic efficiency of the studied medical technologies in clinical trials. The importance of proper selection of economic evaluation models (cost minimization, cost-effectiveness, cost-benefit) in accordance with the purpose of the clinical trial, the primary hypothesis and the selected primary and secondary endpoints is determined. Conclusions. It is determined that there are certain problems of methodological and organizational nature for the development of clinical trials with included сost-effectiveness analysis and economic endpoints. The solution of these tasks should begin at the planning stage of the study by implementing the basic step-by-step recommendations. Innovative treatment technologies that have potential health benefits are often investigated in clinical trials. Thus, the introduction of pharmacoeconomic analysis methods into the structure of traditional clinical trials is an additional important tool to ensure the effective functioning and development of health technology assessment. In further research it is planned to develop scientific and practical approaches to ensure the proper implementation of management processes of сost-effectiveness analysis alongside clinical trial and analysis of data on their results. Keywords: clinical trials; health technology assessment; algorithms; economic models; procedures

The pharmacoepidemiological analysis of the influenza pharmacotherapy in Ukraine

Influenza and other acute respiratory viral infections (ARIs) are the most common among human diseases that require timely medical attention and treatment with the most effective drugs. The aim of the study is pharmacoepidemiological analysis of drugs for the treatment of influenza registered in Ukraine. Materials and methods of research. The study was based on data from the State Register of Medicines of Ukraine, information on the results of the epidemic season of influenza and acute respiratory infections of the Center for Public Health of the Ministry of Health of Ukraine, declared drugs under the International Nonproprietary or Common Name in Ukraine as of January 2021. Methods: retrospective, descriptive and frequency analyzes. Results and discussion. A pharmacoepidemiological analysis of influenza drugs in Ukraine was conducted. It was found that the incidence of influenza and SARS during the study period decreased by 3.1% of the total population. Fatalities due to influenza and SARS increased by 41 cases during the study period, which may be related to the coronavirus pandemic. According to the results of a marketing study of antiviral drugs, it was found that the largest share in the structure of registered trade names are interferons (11 trade names). Conclusions. The analysis of the market showed that among the antiviral drugs registered in Ukraine for the studied period the dominance of domestic drugs is noted - 54% (respectively of foreign origin - 46%). Analysis of the distribution of domestic analogues of antiviral drugs by manufacturers found that the largest (5 and 4 TN) belongs to LLC "Research and production company" Interpharmbiotek and FZ "Biopharma" Ltd., Ukraine, Bila Tserkva. Key words: influenza; pharmacoepidemiological analysis; antiviral drugs

The analysis of the availability of nasal corticosteroids at the regional market

Aim. To analyse the availability of nasal corticostyroids (NC) in the regional market (on the example of Lviv region).Results. It was found that the average retail prices (ARP) of 5 international non-proprietary names of NC in the form of 15 trade names were in the range from 127.35 to 440.13 UAH in 2019, from 158.12 to 461.75 UAH in 2020 and from 187.2 to 562.9 UAH in 2021. The prices of one DDD of the analysed NC ranged from 2.88 UAH to 15.76 UAH in 2019, from 3.27 to 19.5 UAH in 2020 and from 6.5 UAH to UAH 18.76 in 2021. Despite the growth of the ARP, the availability rate for the most NC was higher than one. It was found that the competitiveness of the NC was characterized by annual instability.Conclusions. Based on the study of ARP as a separate package and one DDD of 5 international non-proprietary names of NC in the form of 15 trade names, which were presented in the regional market of Lviv region every month from January 2019 to January 2021, it was found that prices for most NC increased. Analysis of the availability index of NC revealed that for more than two thirds of NC it was higher than one. Thus, the average salary for the analysed period grew faster than the ARP of NC. Using graphical and mathematical methods of competitiveness assessment, it was shown that the price situation and the width of the distribution channel in the regional market of NC was quite unstable, which requires constant monitoring. Key words: nasal corticosteroids; average retail prices; DDD; availability; competitiveness