The aim. To conduct a comprehensive study of biphasic-type suppositories that contain diosmin and hesperidin. Materials and methods. Samples of biphasic-type suppositories with a mass of 4.0 were objects of the study. Pharmacological, technological and analytical research methods were used to directly or indirectly analyze the strength and completeness of the drug activity. Thus, in this work we combined the study of the specificity of the pharmacological action of the drug, experimental verification of the quantitative content of API, analysis of the structural properties of suppositories and study of the profile of the release of active pharmaceutical ingredients. Results. Therefore, based on the obtained data, the most effective dose was 75 mg / kg (in terms of a human dose of 300 mg per suppository). The drug in the selected dose showed a significant therapeutic effect, which significantly exceeded that of the test sample at a lower dose and the reference agent. According to the results of technological studies, it was determined that all samples of suppositories had satisfactory structural and mechanical properties. Studies of the histological structure of the mucous membrane of rats proved that there is a positive effect of treatment with suppositories with diosmin and hesperidin due to the improvement of the normal condition of the mucous membrane, the absence of edema and ulcerative defect. Research of the release profile of active pharmaceutical ingredients showed that the best percentage of release is characteristic of sample 2 (99.8 %) Conclusions. Therefore, suppositories with diosmin and hesperidin in therapeutically dose of 75 mg/kg of animal weight can be used for further research and will be of interest in the treatment of hemorrhoids of both acute and chronic forms

Незважаючи на підвищений попит на синтетичні лікарські засоби, використання субстанцій рослинного походження є перспективним напрямком розвитку фармацевтичного сектору галузі охорони здоров'я України. Субстанціями рослинного походження, що мають широкий спектр дії та можуть використовуватися для лікування захворювань судин, в тому числі і терапії захворювань аноректальної зони-є діосмін та гесперидин. На фармацевтичному ринку України дані субстанції представлені виключно твердими лікарськими формами, що застосовуються для лікування хронічної венозної недостатності. Доцільним є звернення уваги на дослідження складу та технології нової комбінованої лікарської форми з діосміном та гесперидином, що завдяки високим показникам біодоступності може цілеспрямовано вивільняти діючі речовин саме у місці розвитку патологічного процес. Визначення властивостей діосміну та гесперидину буде мати суттєвий вплив на технологію отримання нового лікарського засобу і ґрунтується на комплексному дослідженні. Метою роботи стали фізико-хімічні та фармакотехнологічні дослідження субстанцій діосміну та гесперидину. Результати. В ході виконання поставленої мети було проведено мікроскопічне дослідження субстанцій з наступною побудовою диференціальної кривої розподілу фракцій, вивчено дериватографічні характеристики речовин, проведено дослідження вологопоглинання та розчинності. Була встановлена недостатня розчинність субстанцій діосміну та гесперидину, та високий поріг критичної деструкції речовин. Результати мікроскопічного аналізу свідчать про неоднорідний розподіл частинок з превалюванням декількох фракцій у зразку діосміну та наявність агломерації частинок у гесперидину. Висновки. Таким чином на підставі проведених експериментальних досліджень можна зробити висновок про доцільність подальших досліджень, щодо покращення властивостей субстанцій. Отримані результати матимуть істотний вплив при розробці складу та технології нової лікарської форми з діосміном та гесперидином Ключові слова: діосмін, гесперидин, фармакотехнологічні показники, мікроскопічне дослідження, диференціальна крива розподілу, вологопоглинання, розчинність, дериватографія

The aim of the work was a marketing research of the nomenclature of medicines presented on the pharmaceutical market of Ukraine, which are used to treat diseases of the anorectal zone. The work used graphic, system, marketing and pharmacoeconomic analysis methods. According to medical statistics in Ukraine, there is a rapid increase in the percentage of patients with pathologies of the anorectal zone among people of working age. The reasons for this phenomenon is the lifestyle of a modern person, which leads to an unbalanced diet, a decrease in physical activity and untimely treatment of existing diseases. The great variability of the symptomatic manifestation of pathological processes in diseases of the anorectal zone requires the appointment of effective treatment with groups of drugs with different pharmacological activity. When analyzing the assortment of drugs used to treat diseases of the anorectal zone, it was found that 117 pharmaceutical preparations in various dosage forms were presented on the pharmaceutical market of Ukraine; of which the proportion of suppositories is 17.09%. When analyzing the origin of the main active ingredients of suppositories, it was found that the largest share is made up of active substances of synthetic origin (60%), herbal components are present in 25% of the analyzed preparations, a combination of substances of plant and synthetic origin account for 15%. An analysis of the origin of the manufacturing company allows us to conclude that the share of medicines manufactured in Ukraine is 50%, and the range is presented to foreign manufacturers from Germany, Poland, France, Serbia and Italy. The results obtained indicate that, according to the recommendations for the use of drugs, a treatment course of 1 week is rational. An analysis of treatment regimens suggests that the use of a combination of several drugs from different pharmacological groups significantly increases the total cost and reflects a lack of compliance. The analysis of drugs used to treat diseases of the anorectal zone. The assortment of drugs was studied by the form of release, the origin of the manufacturer, the composition of the dosage form, the origin of the main components and pricing policy. It was found that there is a lack of rectal suppositories of a combined composition that could be used to treat these pathologies. Therefore, as a result of the study, it was concluded that the creation of a new drug for the safe and effective treatment of diseases of the anorectal zone is advisable and relevant. Keywords marketing analysis; pharmaceutical market of Ukraine; diseases of the anorectal zone; suppositories.

In the development of suppositories biphasic media are rarely used. It is due to the occurrence of possible instabilities within the system «dispersed phase and a dispersing medium». To solve such problems, it is rational to use the methods of mathematical planning of the experiment. The method of mathematical planning of the experiment feature is the diversity of approaches to model construction. This means that these methods are theoretically predict the results of a future experiment, analyze the data obtained, prevent the repetition of experiments and optimize the technology of medicine. The aim of the present research was to develop and optimize of quantitative composition of rectal suppositories with diosmin and hesperidin by the method of mathematical planning of experiment. Objects of the study were samples of suppositories of the biphasic type with diosmin and hesperidin. The dispersing medium of these samples consisted of hydrophobic (Witepsol W35 and emulsifiers) and hydrophilic parts (sodium alginate gel with the addition of Ca2+ as a complexing cation). Preliminary results of determining the percentage limits of the hydrophobic part of the dispersed medium were carried out by studying the indicators of the release of active substances from the dosage form and the laser diffraction method. As responses of experiments was used such indicator as: disintegration time, hardness and mucoadhesion. As a result of the studies, the functional dependence of the indicators on the amount of components of the suppository dispersed medium was established. It was found that acceptable values of the responses should conform to the following conditions: hardness and mucoadhesion should be close to the maximum, and the disintegration time – to the minimum. According to the results of the study it was found that the optimal content of the mixture of emulsifiers – 6.29%, solid fat – 39.51%, the hydrophilic part of the biphasic medium – 29.58%. Responses that will provide the system with the necessary structural-mechanical and pharmaco-technological properties are within: y1 (2.713); y2 (22.639); y3 (439.283). The obtained data will be used in further studies to optimize the composition and technology of rectal suppositories with diosmin and hesperidin.