The formulation of the transdermal patch with fulvic acid (FA) on an emulsion basis using pluronic Kolliphor^® p237 as a permeability enhancer was developed and studied for anti-inflammatory properties. FA was isolated from the peat in the Nizhny Novgorod region of Russia and characterized as a potential active pharmaceutical ingredient. In vitro studies of the release of FA from the transdermal patch, as well as the FA penetration through the acetyl cellulose membrane using the Franz diffusion cell, showed its high efficiency (56% and 90%, respectively, in 8 h). In the in vivo experiment, qualitative and quantitative features of the rat knee caused by complete Freund’s adjuvant-induced arthritis (morphological changes, the FA influence on the biochemical indexes) were studied. The inflammatory process that developed within 15 days was accompanied by the activation of antioxidant oxidoreductase enzymes (by 50–70%), the increase in the cross-sectional diameter of the cartilage, and the increase in the values of marker indicators of the process of rheumatoid arthritis. Within 7 days of treatment, under the influence of FA, the values of ESR, RF, leukocytes, C-reactive protein, as well as the biochemical parameters characterizing oxidative stress (SOD, catalase, glutathione reductase, LDH, G6PD) normalized, and the edema reduced. These results may be useful for arthritis treatment using the transdermal patch with FA.

Introduction. Fulvic acid as a fraction of humic substances is a hydrophilic molecule that can form aggregated particles in solutions. This can cause problems in the development of topical formulations such as ointments, gels and transdermal patches. In such cases, the development of formula-tions improving the penetration of small polar molecules through the lipophilic stratum corneum are required. Aim of the report – the development of compositions of transdermal therapeutic system and study of release of humic derivatives from them. Material and methods. Objects of the study: Transdermal patch is a dosage form for external use intended for controlled delivery of a medicinal substance (substances) into the systemic circulation by passive diffusion through intact skin. Fulvic acid (FA) was studied as humic derivatives. De-termination of the release rate of the active substance from the base and modified formulations was carried out according the pharmaceutical article Dissolution for transdermal patches. Determination of the concentration of fulvic acid in the aqueous extracts is carried out using spectrofluorimetry (spectrofluorimeter SolarCM 2203). Results. Emulsion transdermal patches have been developed and investigated. Based on the dissolution test for transdermal patches, the following results were obtained. The amount of FA released from the transdermal patches, with an initial content of 0.016 g, was equal to: (0.0081±0.0002) g (composition 1, Kolliphop p237) in 8.25 hours (495 minutes); (0.0046±0.0003) g (composition 2, Kolliphor p338), for 8.5 hours (510 min); (0.0048±0.0002) g (basic composition), for 6.5 hours (390 min). Conclusions. From the results of the experiment, it can be concluded that the modified composition 1 (Kolliphor p237) showed the best result in the release of fulvic acid in comparison with other compositions.

There is a high demand for the design of fulvic acids (FA) transdermal patches being natural biologically active substances with a wide action. The difficulties in FA transdermal patches creating are due to the peculiarities of FA obtaining with high purity and solubility, the existence of many several polymorphic forms, as well as the problems of their insertion into dosage forms. In this work, we modified the FA isolation as water-soluble polymorph. This operation allowed us to reduce the impurities in the product, to optimize the formulation of the emulsion-based transdermal patches, to provide a quantitative assessment of FA release. Data of IR, 13C NMR, AAS, ICP-AES-spectra, direct and reverse titration of carboxyl groups and phenolic hydroxyls, potentiometry, molecular weight determination by cryoscopy (M.m=740 g/mol), fluorescent analysis, solubility (3.3 mL of water per gram) confirmed the receipt of the desired polymorph. Optimization of the transdermal patches formulations by Response Surface Methodology and release evaluation and kinetics mathematical modeling using a Franz cell showed the preferences of Pluronic Kolliphor p237 as a transcutant. The obtained water-soluble FA can be used as a potential component of transdermal patches with controlled release parameters. Keywords: fulvic acid, transdermal patches, pluronics, release

Medicines based on compounds of iron, copper and zinc occupy a certain place in the pharmaceutical market. A lack of iron in the body can contribute to the development of iron deficiency anemia, and in the case of copper and zinc, a deficiency in the immune response and inflammation caused by lipid peroxidation, which ultimately leads to various joint diseases such as arthritis. The basis of the treatment and prevention of diseases is the use of chelates of salts of iron, copper and zinc, the effectiveness of which largely depends on their stability and the degree of release of trace elements in various parts of the gastrointestinal tract. Therefore, there is a need to create new long-acting drugs with a certain solubility and sufficient bioavailability. This study is devoted to the development of the optimal composition of iron, copper and zinc humate matrix tablets for oral administration.

Разработаны и сравнены составы эмульсионных основ для доставки гидрофильных лекарственных веществ на примере натрия хондроитинсульфата. Приведены результаты теста «Растворение для трансдермальных терапевтических систем» с целью определения количества высвобождаемого хондроитинсульфата натрия из трансдермального пластыря через мембрану. В пробах, взятых через определённый промежуток времени, установлена концентрация вещества методом фотоколориметрии. Разработанные оптимальные полимерные матрицы эмульсионных основ обеспечивают надежное прикрепление трансдермальной терапевтической системы к коже в течение требуемого времени аппликации и не препятствуют высвобождению лекарственного вещества. Скорость высвобождения действующего вещества может быть отрегулирована добавлением дополнительных полимеров. DOI: 10.30906/2073-8099-2022-14-5-3-7