Development of Composition and Technologies of Dental Gel of Meloxicam

BACKGROUND: Dental gels have several advantages over other oral dosage forms. Being a viscoplastic dosage form, the gel, when applied to the damaged area of the gum or mucous membrane, creates a protective film, preventing mechanical irritation, and providing a localized effect of the drug components. AIM: The aim of this work was to develop the composition and technology of the dental gel of meloxicam, the study of the main technological and consumer characteristics, as well as the local irritating effect of the dosage form. METHODS: Dental gels were prepared using purified water, alcohol, glycerol, and buckthorn oil as solvents, gelling agents used were: Hydroxyethylcellulose Natrosol® 250 HHX Pharm, Carbopol® 974P NF Polymer, and solubilizer Poloxamer 407 (Lutrol® F 127). The bioadhesive component and Noveon® Polycarbophil component were used for dental gel preparation. Aspartame was used as sweetener. Menthol and ascorbic acid were used to correct the organoleptic properties of the pharmaceutical composition. The formulated dental gel of meloxicam at a concentration of 7.5% was evaluated for organoleptic properties, pH, rheological characteristics, bioadhesive properties, and stability under the accelerated aging period. The in vivo local irritant effect was evaluated using ten rabbits by cutaneous, subcutaneous, subconjunctival administration, as well as application to the upper palate. RESULTS: Based on the results of studying technological and organoleptic properties, the optimal composition based on the Natrosol® 250 HHX hydroxyethylcellulose gelling agent, glycerol solvent, and purified water in the ratio 1/5 was selected, the composition contains Noveon® bioadhesive in an amount of 2%. The composition has good taste, pH close to pH of saliva has high bioadhesive properties, satisfactory rheological characteristics. The shelf life of the experimental series by accelerated aging was 2 years. The selected composition does not have a local irritant effect. CONCLUSION: A new dosage form of meloxicam was developed – a gel for use in dental practice

Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid

The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved with the help of intravitreal in situ injection systems, which are injected with a syringe into the vitreous body and provide prolonged action of the drug at the focus of inflammation. Under the influence of temperature, the liquid drug undergoes a phase transition and turns into a gel after injection. This ensures its prolonged action. The study aimed to develop an intravitreal in situ cefuroxime delivery system for the treatment of endophthalmitis based on a thermosensitive biodegradable composition of poloxamer 407 and hyaluronic acid. A combination of poloxamer Kolliphor® P407, Kolliphor® P188, and PrincipHYAL® hyaluronic acids of different molecular weights was used as a delivery system. The potency of cefuroxime solid dispersion with polyvinylpyrrolidone-10000, polyethylene glycol-400, and polyethylene glycol-1500 in a 1:2 ratio was studied for prolonged action compared to cefuroxime substance. The experimental formulations were studied for the parameters of gelation temperature in a long-term test (4 months), pH, and release of cefuroxime using dialysis bags. To study the distribution parameter in the vitreous body, an in vitro model (1/13) was developed, which was a hollow agar sphere filled with 1% (w/v) polyacrylate gel. For the superior formulations, a HET-CAM test (chorioallantoic membrane test) was performed to determine the absence of irritant effects. According to the study results, a formulation containing a solid dispersion of cefuroxime:PEG-400 (1:2), the matrix of which contained 18% (w/v) Kolliphor® P407 poloxamer, 3% (w/v) Kolliphor® P188 poloxamer, and 0.5% (w/v) hyaluronic acid (1400–1800), was selected. This sample had an average gelation temperature of 34.6 °C, pH 6.7 ± 0.5, and a pronounced prolonged effect. Only 7.6% was released in 3 h of the experiment, whereas about 38% of cefuroxime was released in 72 h. No irritant effect on the chorioallantoic membrane was observed for any formulations studied

Intranasal Ion-Triggered In Situ Delivery System of Virus-like Particles: Development Using the Quality by Design Approach

The rapid growth in the prevalence of infectious diseases requires timely action from drug developers. In recent years, the COVID-19 pandemic has demonstrated the unpreparedness of the population for such emergencies. The introduction of modern methods of Design of Experiments (DoE) is required to accelerate the process of drug development and bring a drug to market. The main objective of this study was to develop an ion-triggered in situ system for intranasal delivery of VLP using a Quality by Design approach. Based on a literature review and initial studies, the key QTPP, CQA, CPP, and CMA were identified to develop a novel delivery system for virus-like particles. As a result of the studies on the quality attributes of the developed delivery system, an ion-triggered in situ gel meeting all the specified parameters was obtained using the Quality by Design method

Антигепатотоксическая активность липосомального Силибинина

The liposomal form of silibinin was obtained, and its antihepatotoxic activity in mice was studied using a model of acute toxic hepatitis caused by injection of carbon tetrachloride or paracetamol. It was shown that the use of the drug in therapy or prevention regimens leads to normalization of levels of transaminases and total protein in the blood of experimental animals. The results of the study showed that liposomal silibinin when administered intravenously shows a more pronounced hepatoprotective effect compared to intragastric administration of free silibinin. Thus, the effectiveness of the therapeutic action of silibinin can be significantly increased by using its liposomal form. Liposomal drug, in contrast to native silibinin, can be injected directly into the blood that significantly increases its bioavailability.Была получена липосомальная форма силибинина и изучена его антигепатотоксическая активность на мышах с использованием модели острого токсического гепатита, вызванного инъекцией четыреххлористого углерода или парацетамола. Показано, что применение препарата в схемах терапии или профилактики приводит к нормализации уровня трансаминаз и общего белка в крови экспериментальных животных. Результаты исследования показали, что липосомальный силибинин при внутривенном введении проявляет более выраженный гепатопротекторный эффект по сравнению с внутрижелудочным введением свободного силибинина. Таким образом, эффективность лечебного действия силибинина может быть значительно повышена при использовании его липосомальной формы. Липосомальный препарат, в отличие от нативного силибинина, можно вводить непосредственно в кровь, что значительно повышает его биодоступность

ИЗУЧЕНИЕ ТВЁРДЫХ ДИСПЕРСИЙ ФУРАЗОЛИДОНА РЕНТГЕНО-ФАЗОВЫМ МЕТОДОМ

Background: to study the phase composition of the solid dispersion of furazolidone by the X-ray phase method. Method: The study was carried out on the basis of the All-Russian Research Institute of Aviation Materials («VIAM») on an X-ray diffractometer DRON-4 («Burevestnik», Russia) according to OFS 1.2.1.1.0011.15 (state Pharmacopoeia XIV). The initial substance of furazolidone, polyvinylpyrrolidone-10000 (PVP) and their solid dispersions (SD) were studied. Result: the radiograph of the SD is the sum of the peaks of the components. SD, presumably, is a combined system - a solution of furazolidone in a polymer and a colloidal phase of the active substance distributed in a matrix of PVP (solid colloid). Conclusion: the obtained data confirm the assumption that furazolidone loses its crystal structure when its SD is obtained with the polymer under study.Цель: изучить фазовый состав твёрдой дисперсии фуразолидона рентгено-фазовым методом. Метод: Исследование проводили на базе ФГУП Всероссийского НИИ авиационных материалов («ВИАМ») на рентгеновском дифрактометре ДРОН-4 (НПП «Буревестник», Россия) согласно ОФС 1.2.1.1.0011.15 (ГФ XIV). Исследовали исходную субстанцию фуразолидона, поливинилпирролидон-10000 (ПВП) и их твёрдые дисперсии (ТД). Результат: рентгенограмма ТД является суммой пиков компонентов. ТД, предположительно, представляет собой комбинированную систему - раствор фуразолидона в полимере и коллоидную фазу действующего вещества, распределённую в матрице ПВП (твёрдый коллоид). Выводы: полученные данные подтверждают предположение о потере фуразолидоном кристаллической структуры при получении его ТД с исследуемым полимером

THE THE INFLUENCE OF THE EXCIPIENTS ON THE ANTI-INFLAMMATORY EMULGEL BIOPHARMACEUTICAL QUALITY PARAMETERS

Objective: Boswellia serrata dry extract (BSDE) has clinically proved its anti-inflammatory, anti-gout, and analgesic effect. In the course of this study, compositions and technologies of the emulgels, containing dry Boswellia extract, were developed. Materials and Methods: Rheological characteristics of gels were determined with rotational viscosity method using coaxial rotation viscometer Lamy Rheology RM 200. The stickiness was determined using a lever mechanism which separates two preprocessed glass plates of the same area from each other. Spreadability was determined with a weighted amount of gel placed on a glass plate (10 cm × 10 cm), covered with a cover glass of the same size and a 100 g measuring plane placed on top of it. Results: The composition containing 20% of turpentine oil was shown to have the highest yield strength, which can positively affect the aggregative stability of the dosage form. The spreadability of all samples lies within the average value of the spreadability of the commercial gels. The stickiness of all samples was determined to be in the range from 3.6 to 4.9 N. The composition containing turpentine oil showed maximum stickiness after application and its minimum decrease by 5 min. Conclusion: The advantages of the composition including turpentine oil as a solvent for BSDE were experimentally established

ИЗУЧЕНИЕ ОПТИЧЕСКИХ СВОЙСТВ РАСТВОРОВ ТВЁРДОЙ ДИСПЕРСИИ МЕТРОНИДАЗОЛА

Background: to study the effect of obtaining solid dispersions (SD) on the optical properties of metronidazole solutions. Methods: the studied solutions were filtered through Minisart syringe nozzles (Satorius, Germany) with a nylon membrane filter and a pore size of 0.45 microns. The filtered samples were placed in a quartz cuvette (layer thickness 50.0 mm) with the corresponding solution through a hole on the side with a diameter of ≈1 mm (in a light-tight partition between the light source and the wall of the cuvette), a concentrated beam of light was directed. With the help of a Canon 5D MarkII SLR camera, digital images of the Faraday-Tyndall «cone» were taken in a darkened room (exposure time of 20 seconds). Result: opalescence in the form of a bluish-gray cone is observed in solutions of DD metronidazole. Conclusion: the observed Faraday-Tyndall effect confirms the assumptions about the colloidal-dispersed state of metronidazole in the TD solution.Цель: изучить влияние получения твёрдых дисперсий (ТД) на оптические свойства растворов метронидазола. Метод: исследуемые растворы фильтровали через шприцевые насадки Minisart (Satorius, Германия) с мембранным фильтром из нейлона и размером пор 0,45 мкм. Фильтрованные образцы помещали в кварцевую кювету (толщина слоя 50,0 мм) с соответствующим раствором через отверстие сбоку с диаметром ≈1 мм (в светонепроницаемой перегородке между источником света и стенкой кюветы) направляли концентрированный луч света. С помощью зеркальной камеры Canon 5D MarkII в затемнённом помещении делали цифровые изображения «конуса» Фарадея-Тиндаля (время экспозиции 20 сек). Результат: в растворах ТД метронидазола наблюдается опалесценция в виде конуса синевато-серого оттенка. Выводы: наблюдаемый эффект Фарадея-Тиндаля подтверждает предположения о коллоидно-дисперсном состоянии метронидазола в растворе ТД

ИЗУЧЕНИЕ ТВЁРДЫХ ДИСПЕРСИЙ индометацина МЕТОДОМ МИКРОСКОПИИ

Background: to study the effect of obtaining solid dispersions (SD) with polyvinylpyrrolidone-10000 (PVP) on the microcrystalline pattern of indomethacin. Methods: the analysis was carried out at the Department of Analytical, Physical and Colloidal Chemistry of the A.P. Nelyubin Institute of Pharmacy of the I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University). We used a Levenhuk D50L NG digital microscope (made by Levenhuk, China), equipped with a digital camera (2 megapixels) for microphotography, with Levenhuk ToupView software compatible with Windows 7. Substance indomethacin were studied by optical microscopy under a cover glass in a drop of paraffin oil. Under microscopy, recrystallized substance, PVP, etc., a drop of their solution in 96% ethanol was applied to the slide. Microscopy after removal of the solvent. Result: The SD of indomethacin with PVP is a homogeneous system. SD is a solution of indomethacin in a polymer matrix of PVP. Conclusion: the preparation of SD reduces the crystallinity of ndomethaci, improving its dissolution in water.Цель: изучить влияние получения твёрдых дисперсий (ТД) с поливинилпирролидоном-10000 (ПВП) на микрокристаллическую картину индометацина. Метод: анализ проводили на кафедре аналитической, физической и коллоидной химии Института фармации им. А.П. Нелюбина Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет). Использовали цифровой микроскоп Levenhuk D50L NG (фирмы Levenhuk, Китай), оснащённый цифровой камерой (2 Мпикс) для микрофотосъёмки, с программным обеспечением Levenhuk ToupView, совместимым с Windows 7. Субстанцию индометацина микроскопировали под покровным стеклом в капле вазелинового масла. При микроскопии, перекристаллизованной субстанции, ПВП и ТД на предметное стекло наносили каплю их раствора в этаноле 96%. Микроскопировали после удаления растворителя. Результат: ТД индометацина с ПВП представляет собой гомогенную систему. ТД - это раствор индометацина в полимерной матрице ПВП. Выводы: получение ТД снижает кристалличность индометацина, улучшая его растворение в воде

TRENDS OF THE DEVELOPMENT OF HIGHER PHARMACEUTICAL EDUCATION

The dynamic development of the pharmaceutical industry in the Russian Federation is closely connected with training of qualified personnel, which in turn requires modernization of the education programs of higher professional education. Comparative analysis of the field, objects and kinds of professional activity, professional tasks of the pharmacist presented in the current Federal state educational standard (FSES HPE 3) and the new FSES HE 3+ in the specialty «pharmacy» allows to identify the main patterns and trends in the development of the Russian pharmaceutical education. Educational programs developed and implemented by institutions of higher vocational education must meet the requirements of employers for graduates with regard to the transfer of the domestic pharmaceutical industry to international standards

THE DEVELOPMENT AND STUDY OF THE TOXICITY OF SUPPOSITORIES WITH A MODIFIED SUBSTANCE OF INTERFERON ALFA-2B

Objective: To develop a stable composition with the substance of PEGylated interferon alfa-2b, to study technological and biopharmaceutical characteristics of the dosage form, and to conduct preclinical studies on the chronic toxicity and local irritating effect. Methods: Solid fats Witepsol® H15, Witepsol® W 35, Suppocire® BS2X, and Suppocire® BM brands were used as the suppository bases. Polysorbate 80 was used as an emulsifier. Citric acid, ascorbic acid, sodium tetraborate, lactic acid, ethylenediaminetetetraacetic acid, tocopherol acetate was also introduced into the experimental samples. Fourteen experimental samples were screened for biological and technological indicators. Preclinical studies were performed for the optimal composition on the indicators of chronic toxicity and local irritant effect. Results: The study examined the cytotoxic effects on the Vero cell line of selected suppository bases and excipients, namely, pH regulators and antioxidants. With excipients that did not have cytotoxicity we obtained suppository compositions with the following quality indicators: cytotoxicity, specific activity of interferon, time of complete deformation of suppositories and their melting temperature. A total of 14 compositions were studied, of which 5 were selected on the basis of the results for the study of stability. Only one composition turned out to be stable for the time studied. Conclusion: The most stable in terms of “specific activity” was sample 7, its composition: Witepsol® H15 / W35 70/30, polysorbate-80 0.15%, ethylenediaminetetraacetic acid (EDTA) 0.15%, sodium tetraborate 0.15%, tocopherol acetate 3.0%. Preclinical studies, that showed the absence of chronic toxicity and local irritant effect, were performed for this composition