Розробка комбінованого інкапсульованого лікарського засобу на основі налтрексону та дисульфіраму

In the article it is revealed the problem of choice of technology for obtaining the combined drug of prolonged action to ensure continuity of treatment process and relapse prevention of diseases such as drug dependence and alcoholism. In Ukraine and most of the world for the treatment of alcohol and drug dependencies are used disulfiram and naltrexone. In previous studies, the authors have demonstrated promising development of combined injectable drug of prolonged action based on these drugs.The aim of this study was to obtain the combined injectable drug of prolonged action, which would contain a combination of naltrexone and disulfiram for the treatment of combined alcohol and drug addictions by encapsulation method. The objects of our study served as naltrexone, disulfiram and excipients – copolymers of lactic and glycolic acids with different ratios of elementary units, emulsifiers and solvents.Analysis of published data allowed us to determine the recommended therapeutic dose of 250 mg of disulfiram and 200 mg of naltrexone. Based on the information, obtained from patents, it is developed the methodology and conducted experiments to obtain encapsulated substances. Size of the emulsion droplets is regulated by rate of stirring: microscale capsules were formed at a speed of 1000 rev/min and nanoscale capsules were formed at speeds over 2,000 rev/min. Capsules were prepared separately from naltrexone and disulfiram in polymers with PLG (50:50) and PLG (70:30) with a ratio of polymer to the drug under 1:2. Morphological characteristics of microcapsules were determined by light microscopy.The methods of quantitative and qualitative determination of disulfiram in microcapsules are proposed. Prolonging the release of naltrexone is confirmed through test "Dissolution". Also, it is worked fundamental technological scheme of production. Advantages and disadvantages of the proposed technology are determined.To determine the toxicity and pharmacological activity of obtained microcapsules combined with alcohol and drug addiction it is started preclinical study (Wistar rats and white mice line Balb/c). By the results of this study it will be conducted preliminary comparative analysis of the pharmacological action of drugs Naltetlong and created combined encapsulated drug from naltrexone and disulfiram provided by this technology.На основе анализа литературных источников, патентного поиска и собственных экспериментальных исследований авторов статьи была разработана оптимальная методика получения капсул микро- и наноразмеров, содержащих налтрексон и дисульфирам, для использования в виде порошков для инъекций. Вспомогательными веществами служили сополимеры молочной и гликолевой кислот. Обработана и предложена технологическая схема процесса производства препарата.На основі аналізу літературних джерел, патентного пошуку та власних експериментальних даних авторів статті була розроблена оптимальна методика одержання капсул мікро- та нанорозмірів, що містять налтрексон та дисульфірам, для застосування у вигляді порошків для ін’єкцій. Допоміжними речовинами було обрано кополімери молочної та гліколевої кислот. Опрацьовано та запропоновано технологічну схему процесу виробництва препарату