АНАЛІЗ АСОРТИМЕНТУ АКТИВНИХ ФАРМАЦЕВТИЧНИХ ІНГРЕДІЄНТІВ, ЗАРЕЄСТРОВАНИХ НА РИНКУ УКРАЇНИ

The aim of the work. To analyze and structure the registered on market of Ukraine active pharmaceutical ingredients assortment. Materials and Methods. Methods of content analysis, structuring, comparative and graphical generalization of data from the State Register of Medicines and pharmaceutical inserts were applied. Results and Discussion. 2100 trade names of active pharmaceutical ingredients, that are manufactured in 51 countries, are registered on pharmaceutical market of Ukraine. It is established that the level of domestic ones is over 16 %, 1/5 of their total number is manufactured on JSC “Liktravy” (medicinal plant raw materials). Indian companies predominate among foreign manufacturers (29.1 %). The leaders are Hetero Drugs Limited (5.9 %) and Hetero Labs Limited (5.5 %) companies. The absence of domestic active pharmaceutical ingredients in the composition of analyzed strategically important registered drugs of Ukrainian production (blood and blood forming organs (groups B01, B02, B05 according to the ATC classification), systemic hormonal preparations (groups H01, H02), antiinfectives for systemic use (groups J01, J02, J04)) was revealed in the majority. Conclusions. The advantage of foreign synthetic active pharmaceutical ingredients with the share of 71.4 % is noted according to the results of registered on market of Ukraine active active pharmaceutical ingredients assortment analysis. Plant trade names (55.8 %), almost half of them (44.4 %) are medicinal plant raw materials, predominate among the domestic active pharmaceutical ingredients. The share of Ukrainian active pharmaceutical ingredients in the composition of studied groups of drugs is extremely small. Taking urgent measures for adjustment and optimization of production of active pharmaceutical ingredients that are components of strategically important groups of drugs, is necessary.Мета роботи. Аналіз і структурування асортименту активних фармацевтичних інгредієнтів (АФІ), зареєстрованих в Україні. Матеріали і методи. Застосовано методи: контент-аналізу, структурування, порівняльного та графічного узагальнення відомостей Державного реєстру лікарських засобів та інструкцій для медичного застосування. Результати й обговорення. На фармацевтичному ринку України зареєстровано 2100 торгових назв АФІ, вироблених на підприємствах 51 країни. Встановлено, що частка вітчизняного виробництва складає дещо більше 16 %, з них 1/5 виготовлено на базі ПрАТ «Ліктрави» (лікарська рослинна сировина). З-поміж іноземних переважають виробники Індії (29,1 %), серед яких лідерами є Гетеро Драгз Лімітед (5,9 %) та Гетеро Лабз Лімітед (5,5 %). У більшості проаналізованих стратегічно важливих зареєстрованих лікарських засобів українського виробництва (засобів, що впливають на систему крові на гемопоез (групи В01, В02, В05 згідно АТС-класифікації), препаратів гормонів для системного застосування (групи Н01, Н02), протимікробних засобів для системного застосування (групи J01, J02, J04)) виявлено відсутність вітчизняних АФІ. Висновки. За результатами аналізу асортименту зареєстрованих АФІ встановлено перевагу іноземних синтетичних номенклатурних позицій (71,4 %). Серед вітчизняних АФІ переважають рослинні (55,8 %), з яких майже половина (44,4 %) є лікарською рослинною сировиною. Частка українських АФІ у складі окремих досліджених груп лікарських засобів є надзвичайно малою, що зумовлює необхідність термінових заходів для налагодження та оптимізації виробництва тих АФІ, які є складовими стратегічно важливих груп лікарських засобів

TECHNOLOGICAL ASPECTS OF TABLETS CREATION BASED ON FLAMMULINA VELUTIPES BIOMASS DRY POWDER

The aim of the work. To study the pharmaco-technological properties of granulate and tablets based on Flammulina velutipes biomass dry powder, to develop the composition and technology of the medication. Materials and Methods. Research of granules and tablets pharmaco-technological properties (sieve analysis, bulk density, tapped density, compressibility index, Hausner ratio, flowability of tablet mass, average weight, resistance to crushing, friability and disintegration of tablets) was carried out in accordance to the requirements of State Pharmacopoeia of Ukraine 2nd edition. Results and Discussion. The determined pharmaco-technological parameters of the granulate indicate good values ​​of the bulk density, tapped density, compressibility index, Hausner ratio and flowability. An intermediate product undergoes a tabletting process to produce a qualitative finished product of satisfactory appearance (plain, cylindrical tablets with a facet, yellowish-white color with brown inclusions, with a height of 4 mm, and diameter of 10 mm), a constant average mass (1.0 g), and strength (68 N). Conclusions. The pharmaco-technological properties of tablet mass (granulate) and Flammulina velutipes biomass dry powder tablets (sieve analysis, bulk density, tapped density, compressibility index, Hausner ratio, flowability, average weight, resistance to crushing, friability and disintegration) were studied. The composition and technology of Flammulina velutipes biomass dry powder tablets have been developed, pharmaco-technological parameters of their quality have been studied, technological block diagram of industrial production has been developed

OBSERVATION OF MEDICINES FOR THE TREATMENT OF DIAPER DERMATITIS ON THE PHARMACEUTICAL MARKET OF UKRAINE

Introduction The neonatal period is the most critical age. There is a high incidence of children in the first year of life on diseases of the skin and subcutaneous tissue. Recently, we can see an increasing proportion of morbidity with atopic dermatitis (10-20%) [1], contact and diaper dermatitis (25%-50%) [5]. Most cases are associated with genetic penchant, an excessive eating of exotic vegetables and fruits, a high frequency of feeding with artificial mixtures etc. [6]. Diaper dermatitis (DD) is an inflammatory reaction of the child`s skin as a result of the mechanical, physical, chemical and microbial factors. It consists of erythema with maceration and may include papules, erosions, and even ulcerations, when severe. The convex surfaces of the newborns buttocks, genitalia, lower abdomen and upper thighs are the places of the greatest affection [3,8]. Disease can occur under conditions of: late diapers changing, mechanical friction, usage of some care products, transition from breastfeeding to artificial feeding, individual sensitivity of the child`s skin, usage of antibiotics [7,8]. Despite the wide variety of drugs that have been successfully used in dermatology, the amount of drugs for the diaper dermatitis treatment is not enough. So, the aim of our work was to analyze the range of medicines for the treatment of DD, that are presented at the pharmaceutical market ofUkraine. The object of the study was the information of the State register of drugs ofUkraine, formed by “State expert center of the Ministry of health ofUkraine”. Methods of research: search, analysis, generalization and systematization of data. Results and discussion According to the ATC classification, the range of medicines for the treatment of diaper dermatitis belongs to the group D – dermatological products and consists of several groups: D01 (antifungals for dermatological use), D02 (emollients and protective), D03 (preparations for treatment of wounds and ulcers), D06 (antibiotics and chemotherapeutics for dermatological use) and D07 (corticosteroids, dermatological preparations) [4]. There are 18 drugs, which are used for DD treatment according to the State register of medicines (at 1 December 2016). They are divided into 5 subgroups according to the ATC-classification.  Most of them are D03 group drugs (33,3%) – preparations for treatment of wounds and ulcers (“Panthecrem”,” Happyderm-Zdorovie”, “Panthenol”, “Panteхol Jadran”, “Bepanten”, “Panthenol-Ratiopharm”) and D07 (27,8%) – corticosteroids, dermatological preparations (“Betlieben”, “Hydrocortisone”, “Locoid Crelo”, “Locoid Lipokrem”, “Cutivate”). Among the components of formulation of the studied drugs the greatest proportion belongs to such active pharmaceutical ingredients as dexpanthenol –  46,7%, zinc oxide – 20,0%, hydrocortisone – 20,0%, clotrimazole – 6,6% and fusidic acid – 6,7%. Analysis of drugs for the DD treatment, depending on the type of dosage form (DF) showed that drugs are represented by the four DF. The greatest number have the soft dosage forms (ointments – 47,4% and creams – 42,1%). The assortment of this group of drugs is being shaped by three national and twelve foreign manufacturers. Among Ukrainian manufacturers the lider is Public Joint-Stock Corporation (PJSC) “Fitofarm” (50%), among foreign manufacturers – “Jadran” Galenski Laboratorij d.d., Croatia (14,3%) and Temmler Italia S.r.l., Italy (14,3%). By legal status 42% of drugs used for the treatment of diaper dermatitis are released from drugstores and their structural units with prescription [2,4]. Conclusions There were 18 drugs, which are used for treatment of diaper dermatitis according to the State register of medicines (1 December 2016). 95% of them are intended for the treatment of both children and adults and more than 20% of drugs can be used only for children in age 3-6 months. It should also be noted that the nature of the disease is influenced by the individual characteristics of the child, this requires a differentiated approach to the choice of therapy in each case. The creation of an effective pediatric medicines both industrial production and extempore formulation according to the requirements of good manufacturing practice and good pharmacy practice is an actual problem

ВИВЧЕННЯ ВПЛИВУ ДОПОМІЖНИХ РЕЧОВИН НА ФАРМАКО-ТЕХНОЛОГІЧНІ ВЛАСТИВОСТІ ТАБЛЕТОК СУХОГО ПОРОШКУ БІОМАСИ FLAMMULINA VELUTIPES

The aim of the work. Studying the impact of four groups of excipients (fillers, disintegrants, lubricants and glidants, binders) on the pharmaco-technological properties of Flammulina velutipes biomass dry powder tablets. Materials and Methods. Research of the impact of excipients on such parameters as surface quality, uniformity of weight, resistance to crushing, friability and disintegration of tablets was carried out in accordance to the requirements of State Pharmacopoeia of Ukraine 2nd edition using the method of mathematical experiment planning.Results and Discussion. Сonclusions about the impact of excipients on F. velutipes biomass dry powder tablets quality indicators were made based on comparisons of multiple levels of studied factors. When using any of representatives of the groups of excipients we obtained similar results of impact on tablet weight uniformity. Satisfactory results of tablet friability were obtained in 13 series of experiments, 5 of them had an average of less than 0.5 %. Compressed F. velutipes biomass dry powder tablets had different strength values, only in 9 series of experiments the index was above 50 N. 7 unsatisfactory series of the preparation were found during the study of the effect of excipients on the disintegration of tablets.Conclusions. The influence of four groups of the excipients on such pharmaco-technological properties of Flammulina velutipes biomass dry powder tablets as surface quality, uniformity of weight, resistance to crushing, friability and disintegration was found. Optimal representatives of the studied groups of excipients (powdered sugar, kaolin, stearic acid, 2 % starch paste) were selected for the production of Flammulina velutipes biomass dry powder tablets by the wet granulation method.Мета роботи. Вивчити вплив чотирьох груп допоміжних речовин (наповнювачі, розпушувачі, змащувальні та ковзні, зв’язуючі) на фармако-технологічні властивості таблеток сухого порошку біомаси Flammulina velutipes.Матеріали і методи. Дослідження впливу допоміжних речовин (ДР) на такі показники, як зовнішній вигляд, однорідність маси, стійкість до роздавлювання, стираність та розпадання таблеток проводили відповідно до вимог ДФУ 2 видання. Вивчення чотирьох груп ДР здійснювали за допомогою математичного планування експерименту.Результати й обговорення. На підставі множинних порівнянь рівнів вивчених факторів зроблено висновки про вплив ДР на показники якості таблеток сухого порошку біомаси F. velutipes. При використанні будь- якого із представників груп ДР одержували близькі результати впливу на однорідність маси таблеток. Задовільні результати стираності таблеток одержано у 13 серіях дослідів, з них 5 мали середній показник менше 0,5%. Спресовані таблетки сухого порошку біомаси F. velutipes мали різні показники міцності, лише у 9 серіях дослідів показник був вищим 50 Н. При вивченні впливу ДР на розпадання таблеток виявили 7 незадовільних серій препарату.Висновки. Встановлено вплив чотирьох груп ДР на такі фармако-технологічні характеристики таблеток сухого порошку біомаси F. velutipes, як зовнішній вигляд, однорідність маси, стійкість до роздавлювання та розпадання. Відібрано оптимальні представники досліджуваних груп ДР (цукор білий подрібнений, глина біла, кислота стеаринова, 2 % крохмальний клейстер) для отримання таблеток сухого порошку біомаси F. velutipes методом вологого гранулювання

DETERMINATION OF PHYSICAL AND PHARMACO-TECHNOLOGICAL PROPERTIES OF FLAMMULINA VELUTIPES BIOMASS DRY POWDER

Introduction. An evaluation of the physical, chemical and technological properties of a drug substance is usually the first step in the development of a solid dosage form, because these parameters allow to predict problems which may occur at the stage of formulation, testing and manufacture. One of the most important properties of the substance is flowability, that affects such processes as transfer, storage, blending and compaction of the material. Flowability depends on a number of factors: shape and particle size, fractional (granulametric) composition, bulk density and tapped density, angle of repose etc. Recently, micro- and macromycetes attract the attention of scientists as a new source of important biologically active substances with a wide spectrum of pharmacological action. Medicinal and edible mushroom Flammulina (F.) velutipes has a long history of usage in Japan and China folk medicine as the immune-stimulating, anti-cancer, antioxidant and antiviral agent. Previous studies have shown that the mushroom’s biomass has immunomodulatory properties, shows no toxic effects on animals and is a promising substance for drugs and health care facilities development [1, 5, 6]. Thus, the purpose of this work was to study the physical and pharmaco-technological characteristics of medicinal mushroom’s Flammulina velutipes powdered dry biomass for the possibility of its further usage in the new drugs developing. Materials and methods The object of the study was F. velutipes biomass, obtained by biotechnological synthesis (cultivation on the amaranth flour aqueous suspension). The biomass was separated and dried in a vacuum freeze dryer Cryodos-500 (Terrasa, Spain). Substance was grinded in a laboratory mill for 5, 10, 15, 20, 25, 30 and 35 seconds. Determination of the particle size was made by sieving through a set of standard sieves №1400, 355, 180, 125 [4]. Shape, size and surface properties of a powder were studied using optical microscope XSM-20, supplied with a eyepiece-micrometer with 400 magnification [2]. We used four methods to determine the biomass flow properties – compressibility index, Hausner ratio, angle of repose and the rate of flow through the funnel (flowability) [3]. Results and discussion Dried biomass was grinded by laboratory mill to the formation of a visually homogeneous yellow-brown powder (optimal duration of grinding was 30 seconds). According to the requirements of Ukrainian State Pharmacopoeia F.velutipes biomass dry powder is moderately fine powder. The main fraction of biomass is a powder in the form of small conglomerates of translucent crystals and their irregular particles with pointed edges and complex (rough) surface with the size of 108-350 micrometers (before sieving) and 126-223 micrometers (after sieving through sieves №355 and №180). The results of F. velutipes dry biomass flow properties determination show that the material has fair flowability and is acceptable for manufacturing purposes [7, 8]. So, we can assume that to produce solid dosage forms based on F. velutipes biomass dry powder it is possible to use the method of direct compressing in the case of dry excipients addition. Conclusions 1. The physical and pharmaco-technological properties of the substance – medicinal and edible mushroom’s F. velutipes biomass dry powder (fractional composition, bulk density, tapped density, compressibility index, Hausner ratio, angle of repose, flowability) were identified. 2. It was established, that the substance has pharmaco-technological properties that require the introduction of excipients for their correction during pressing. 3. The results are important for further research on the development of composition and technology of tablets based on F. velutipes biomass dry powder