The aqueous solutions of ethylene oxide-propylene oxide block copolymers (poloxamers) with a molecular weight of (2.2–15.0) × 10 3 and a relative content of propylene oxide units of 19.9–57.0 mol % are studied by rheoviscometry and dynamic light scattering. The temperature and concentration dependences of the properties of solutions are investigated, and the features of their thermoreversible behavior in a wide range of polymer concentrations (4.7–47.2 vol %) and temperatures (15–75°С) are described. A novel type of the thermoreversible behavior previously unknown for these objects is distinguished which consists in the extremum change in the dynamic viscosity with increasing temperature. This behavior is analyzed within the framework of concepts regarding the micellar structure of solutions and is associated with a change in the hydrodynamic size of poloxamer micelles. The effect of molecular weight, ratio of comonomer units, and temperature on critical poloxamer concentrations, limiting manifestation of the novel type of the thermoreversible behavior of solutions, is characterized quantitatively.

Introduction. Ivermectin is an antiparasitic drug that has been widely used in veterinary medicine. Parasitic diseases of farm animals cause great economic damage and pose the risk of human infection. Prolonged dosage forms of ivermectin are effective against them. The first step in the creation of such a drug was the preparation and study of polymeric microparticles of polycaprolactone with encapsulated ivermectin. Aim. Obtaining polymeric microparticles of polycaprolactone with encapsulated ivermectin using a continuous flow-through unit. Materials and methods. The object of the study was microparticles of polycaprolactone with encapsulated ivermectin obtained on a continuous flow-through unit. Determination of the average particle size and size distribution was carried out by the method of laser diffraction. Microscopy was used to visually assess the shape and size of the microparticles. UV – spectrophotometry was use to quantitative determination of ivermectin. Results and discussion. Polymeric microparticles of polycaprolactone with encapsulated ivermectin was obtained and had an average size of 126.63 ± 42.67 μm and contained 32,73–62,00 % of ivermectin. Suspensions prepared from the obtained microparticles were passed through a 20G injection needle without noticeable resistance, which indicates the possibility of their use as the basis of an injectable preparation. Conclusion. Obtained results confirm the possibility of using flow-through dispersion using a device developed by us for obtaining polycaprolactone microparticles with encapsulated ivermectin, which are suitable for injection. Thus, the results obtained make it possible to continue studies of microparticles and create a drug based on them.

Introduction. Ivermectin is known as a veterinary agent with a wide spectrum of action against endo-and exoparasites of farm animals, which makes its use promising. Therefore, the possibility of creating prolonged parenteral dosage forms using polymer biodegradable carriers is currently being investigated. To carry out their quality control, a method of quantitative determination of the active substance is necessary. Most of the previously proposed methods are characterized by time-consuming sample preparation, complex composition of the mobile phase or a long analysis time, therefore, during the development of an injectable prolonged preparation of ivermectin based on polycaprolactone microparticles, a new method for the quantitative determination of ivermectin was proposed, which is simple and suitable for use in production.Aim. Development of a method for the quantitative determination of ivermectin in the composition of polycaprolactone microparticles and its validation.Materials and methods. Microparticles with ivermectin were used as the object of the study. The method of quantitative determination of ivermectin in the test sample was developed on a high-performance liquid chromatograph Dionex UltiMate 3000 (Thermo Fisher Scientific, USA), equipped with a diode-matrix detector.Results and discussion. In this paper, various conditions for the quantitative determination of ivermectin in the composition of polymer microparticles are studied. Based on the obtained data and results, a method has been developed that has optimal sample preparation and analysis conditions.Conclusion. As a result of the development, the conditions for the analysis were selected, which allow us to evaluate the quantitative content of ivermectin in the sample. The method was validated for the parameters specificity, analytical area, linearity, trueness, repeatability, intermediate precision.

Introduction. Acute toxicity of naltrexone hydrochloride nasal spray during intragastric administration to mice and local irritant effect on rabbits was studied. At all stages of the experiment, observations were made on the General condition of the animals. The state of homeostasis was evaluated using functional, hematological and morphometric methods. According to the results of research, there was no local irritant effect on the eyes of rabbits, as well as no toxic effect of high doses of the drug on animals. Introduction. Naltrexone hydrochloride in doses of 1.5– 5 mg/day has shown its effectiveness in the treatment of a number of diseases. Due to the lack of such a "low-dose" naltrexone registered on the pharmaceutical market, we have developed the composition of the nasal spray naltrexone hydrochloride. One of the stages of our research is to study the safety of the drug being developed. The first step in this direction was to study its acute toxicity and local irritant effect.Aim. Study of acute toxicity and local irritant effect of naltrexone hydrochloride nasal spray.Materials and methods. The object of the study was a nasal spray of naltrexone hydrochloride. Acute toxicity studies were performed on outbred adult mice (females). Study of local irritant effect on Soviet chinchilla rabbits (males).Results and discussion. The study of acute toxicity showed that the drug, at a dose significantly higher than the estimated maximum daily therapeutic dose for humans, did not have a significant toxic effect on the body of laboratory animals. The presence of a local irritant effect in the studied drug was not established in the framework of the experiment.Conclusion. As part of the experiment, the drug under study did not have a local irritant or toxic effect on the animal body. The results obtained allow us to continue the development and study of the nasal spray naltrexone hydrochloride.

Introduction . Naltrexone hydrochloride belongs to µ-opioid receptor antagonists and is widely used in the treatment of alcohol and drug addiction at an oral dose of 50 mg/day. It is also a blocker of other receptors – opioid growth factor and Toll-like factor, which is especially evident at doses of 1.5–5 mg/day. This allows it to be used to treat diseases associated with impaired immunity. Text . To date, there is a significant amount of data indicating the effectiveness of naltrexone hydrochloride administered orally in doses from 1.5 to 5.0 mg per day for the treatment of significant diseases such as AIDS, cancer, autism, multiple sclerosis, etc. However, on the pharmaceutical market still lacks a drug that provides such doses. Due to the fact that oral administration of naltrexone is associated with its first-pass hepatic metabolism and the formation of significant amounts of substances that cause side effects of neuropsychiatric effects and gastrointestinal disorders, as well as the possible effect of naltrexone and its metabolites by other drugs, which in large amounts are used for these diseases, the creation of a parenteral dosage form is relevant. Conclusion . The review presents current research in the field of low-dose naltrexone application, its mechanisms of action, and considers possible areas of application in medical practice. The disadvantages of oral administration are noted and an alternative route of administration such as intranasal is considered. Approaches to the development of a finished dosage form – nasal spray, are implemented when selecting the optimal content of the active substance and auxiliary components of the drug. The most promising is the creation of a drug based on thermoreversible polymers with a naltrexone hydrochloride content of up to 3,0 %.

Introduction. Naltrexone, an antagonist of µ-opioid receptors, is promising for the treatment of various autoimmune and oncological diseases when used in doses of 1.5–5 mg/day. To date, there are no medications that provide such dosages of naltrexone.Aim. Development and validation of a method for the quantitative determination of naltrexone hydrochloride in a nasal spray by high performance liquid chromatography (HPLC).Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. The quantitative determination of naltrexone in the test sample was developed using a Dionex UltiMate 3000 high-performance liquid chromatograph (Thermo Scientific, USA) equipped with a diode-matrix detector.Results and discussion. The possibility of using isocratic and gradient chromatographic modes for the quantitative determination of naltrexone hydrochloride in the nasal spray was studied. Based on these results, a new method of determination using the gradient mode is proposed, which allows minimizing the influence of the polymer component in the test sample on the analysis results.Conclusion. A new technique of high-performance liquid chromatography (HPLC) is proposed that allows identification and quantification of naltrexone hydrochloride in a nasal spray containing a high concentration of water-soluble heat-sensitive poloxamer as a thickener. The developed method was validated according to the parameters: correctness, precision, specificity, linearity.

Исследована иммунобиологическая активность препарата ПневмоВик на основе сополимера 2-метил-5-винилпиридина и N-винилпирролидона против экспериментальной пневмококковой инфекции. Для иммунизации мышей использованы: препарат ПневмоВик, содержащий сополимер 2-метил-5-винилпиридина с N-винилпирролидоном (500 мкг) и капсульный полисахарид (5 мкг) S. pneumoniae серотип 14 (ПС Pn14); капсульный полисахарид S. pneumoniaе серотип 14, полученный из культуральной жидкости при выращивании штамма № 883 в полусинтетической питательной среде; коммерческая вакцина Превенар-13, содержащая капсульные полисахариды 13 серотипов пневмококка. Через 48 ч после заражения у животных наблюдалось уменьшение количества бактерий в ткани легких до 9,3 · 104 у животных, иммунизированных ПневмоВик и ПС Pn14, и до 4,4 · 103, иммунизированных Превенар-13. При этом у животных контрольной группы высевалось до 4,3 · 106 бактерий. При иммунизации ПневмоВик уровень антител возрастал к 21-му дню после иммунизации независимо от препрата, использованного для приготовления иммуносорбента. Во весь период наблюдения уровень антител к ПневмоВик был выше уровня неиммунных и контрольных мышей. Динамика развития инфекционного процесса при интраназальном заражении напрямую зависит от наличия иммунного процесса, развившегося в результате предварительной иммунизации. Иммунизация мышей препаратом ПневмоВик вызывала образование антител, однако уровень их повышался незначительно, что, вероятно, связано с недостаточной дозой или недостаточно быстрым высвобождением активного вещества (ПС).

Introduction. In order to standardize the quality indicators during the expected shelf life of the developed drug naltrexone hydrochloride in the form of a nasal spray containing a high concentration of poloxamer and benzalkonium chloride as a preservative, a microbiological study was carried out. The possibility of using the membrane filtration method for testing prototypes recommended by the State Pharmacopoeia XIV.Aim. Study and selection of test conditions for the «microbiological purity» indicator of nasal spray samples containing naltrexone hydrochloride.Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. When analyzing the microbiological purity, the membrane filtration method recommended in the State Pharmacopoeia XIV.Results and discussion. As part of the study, it was found that the samples of the drug meet the requirements for a microbiological indicator for drugs of category 2. Testing the suitability of the method for samples of the dosage form showed that the antimicrobial effect of the drug was completely removed by washing the filter, which was proved by inoculation of indicator test microorganisms, the quantitative and qualitative nature of growth, which did not differ from the control without the drug.Conclusion. As a result of the studies carried out, the optimal test conditions for the «Microbiological purity» indicator for the nasal spray containing naltrexone hydrochloride were selected and substantiated.

Introduction. Benzalkonium chloride is widely used as a conservation agent in medicines. For quantitative determination, the methods described in the European and American Pharmacopoeias by chromatography using columns with nitrile sorbent are often used. However, in order to unify the methods and simplify the quality control technology in the production process, it is advisable to adapt the existing methods for new goals and objectives.Aim. To develop a method for the quantitative determination of benzalkonium chloride in a nasal spray containing a thermosensitive polymer Poloxamer 407 and validate it.Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. The quantitative determination of naltrexone in the test sample was developed using a Dionex UltiMate 3000 high-performance liquid chromatograph (Thermo Fisher Scientific, USA) equipped with a diode-matrix detector.Results and discussion. The paper explored the possibility of using an earlier developed method for the quantitative determination of naltrexone hydrochloride for the quantitative determination of benzalkonium chloride in the composition of a nasal spray. Based on the results obtained, changes were made to the quantitative determination method, and the sample preparation of the samples under study was adapted.Conclusion. As a result of the studies carried out, the most acceptable conditions for the preparation of the nasal spray for the quantitative determination of the preservative were selected. The developed technique provides for the chromatographic conditions previously used for the determination of naltrexone hydrochloride, which makes it possible to use the equipment as efficiently as possible in the analysis of the finished drug. The method has been validated and its specificity, linearity, correctness and precision have been proven.

The work is devoted to the development of nasal spray containing naltrexone hydrochloride. Naltrexone in doses of 3-5 mg/day acts on the opioid growth factor receptor (OGFr) and toll-like receptor 4 that makes it promising for use in the complex therapy of autoimmune diseases and conditions caused by impaired immunity. To prevent leakage of the drug from the nasal cavity, the thermosensitive poloxamer (Kolliphor® P 407) was introduced into its composition. The dynamic viscosity was studied of model samples in the temperature range of 7-37 °C. The rate of dialysis and the degree of release was investigated of naltrexone. Selected the optimal composition to create a comfortable to use drug «Naltrexone hydrochloride, nasal spray», 25 mg/ml.

The review is about on polymers used as embol for vascular occlusion. Existing and developed means for embolization vascular were considered. Particular attention is paid to polymers and compositions on their basis, which it is capable of forming gel structures suitable for occluding vessels.

The study is devoted to novel manufacturing method of preparation of polymeric microparticles, loaded by naltrexone base, in flow through regime. Special module construction was developed for providing emulsification in continuous regime. Focusing on production of polymeric microparticles with characteristics, compatible with characteristics of the pharmaceutical Vivitrol and its native analogue, parameters of encapsulation process were defined. An ability of prepared microparticles to prolonged drug release during 28 days was demonstrated.

The work is devoted to the development of novel ophthalmic drug prolonged action in the treatment of cataract of different genesis, degeneration and corneal injury. The results showed the possibility of creating an ophthalmic gel based on carbomers with the addition taurine. The resulting preparation was studied on the basic parameters that demand for ophthalmic dosage forms.

Comparative studies of drug Nalvitrole (Lyophilisate for preparation of suspension for intramuscular introduction of the prolonged action, 380 mg (LLC «DECO» Company) and reference drug Vivitrol (Powder for preparation of suspension for intramuscular introduction of the prolonged action, 380 mg (Alkermes, Inc., USA.) were conducted. The test drug Nalvitrole and comparison drug Vivitrol have equal toxicity without local irritative effects.

This review is about nonsteroidal anti-inflammatory drugs and different approaches to development of pharmaceutical forms for controlled nonsteroidal anti-inflammatory drug release. Natural and synthetic biocompatible polymers used as drug carriers were considered. Different methods used for production of polymeric microparticles and formulations of nonsteroidal anti-inflammatory agents based on them were discussed. Characterization of microparticles with encapsulated nonsteroidal anti-inflammatory agents was given.

Medicines used for the treatment of drug addiction nowadays are ineffective. In the last decade, various schools around the world are developing a new approach: the therapeutic vaccine for the treatment of drug addiction. The vaccine injection raises the production of specific antibodies that bind to the drug when it is used and substantially reduces its concentration in the brain. The review describes the main approaches to the design of anti-drug vaccines, their composition, the problems faced by researchers in their development.

В обзоре описаны особенности и перспективы применения в офтальмологии микро- и наночастиц и систем на их основе. Рассмотрены строение и состав микро- и нанокапсул (в том числе, липосом, ниосом, полимерсом и коллоидосом), микро- и наносфер, микроэмульсий и дендримерных наночастиц. Указаны основные методы получения рассматриваемых микро- и наночастиц, способы их введения в область глаза, а также описано их действие на подопытных животных и человека. В заключение обозначены основные направления научно-практических работ в области создания лекарственных препаратов офтальмологического применения на основе микро- и наночастиц.

Purpose of the research — to conduct analysis of the status and perspective of application of prolonged forms of anthelmintic drugs in veterinary.Materials and methods. On the topic of development and application of prolonged forms of anthelmintic in veterinary was conducted the analysis of 27 literature sources including 23 foreign authors. Were analyzed the data about kinetics of avermectins and praziquantel in the animals body and comparative results about dependence and correlation of pharmacokinetic parameters with their anthelmintics efficiency.The results and discussion. Prolonged forms of avermectins which prevent the infections for long period are developing to prevent infection of animals during grazing season. Attempts to create prolonged dosage forms of praziquantel to prevent the Schistosoma japonicum infections are currently in progress. Was shown the possibility of obtaining polymeric microspheres, which contains ivermectins in the form of implants. As solvents are used N-methylpyrrolidone, triacetin, benzyl benzoate etc. Mixes of composite based on sucrose, acetate isobutyrate and polylactic acid is offered for prolongation of the action of ivermectin, which is provides release of ivermectin within 80 days. Were described prolonged forms of praziquantel as the implants on a base of polycaprolactone and it’s mix with polyethylene glycol, which is obtained by extrusion of a melt of a mixture of praziquantel and polymers.

The work is dedicated to the production of polymer suspensions using ultrasonic dispergation in a flow mode. An apparatus was designed on the basis of a Russian flow ultrasonicator. The applicability of this apparatus for obtaining aqueous dispersions of polymeric micro- and nanoparticles by means of one-step emulsification followed by solvent extraction / evaporation was demonstrated. The influence of the process parameters on the characteristics of the obtained suspensions was studied. The particle size distribution and the average size of the resulting particles were evaluated by using Delsa Nano S, Beckman Coulter laser analyzer (USA). The dependence of the average diameter of the suspension particles on the stabilizer concentration and on the change of the phases feed rate was shown. When polyvinyl alcohol was used as a stabilizer in the concentration range 0.5-2%, the average particle size was 30-400 nm. The feed rates of the aqueous and organic phases affect the nature of the particle size distribution.