No abstract

Background. The search for technology or the use of excipients for the development of drugs containing poorly soluble pharmaceutical substances is an urgent task of pharmacy. According to the biopharmaceutical classification system, resveratrol belongs to group 4: the substance has low solubility and low permeability. Therefore, one of the priorities in the development of drugs with resveratrol is to increase its solubility and, as a result, increase its permeability. The article presents the results of physicochemical studies of resveratrol compositions with solubilizers (poloxamer 407, polysorbate 80, methyl-beta-cyclodextrin) after dissolution in a common solvent followed by evaporation.Aim. Obtaining compositions of resveratrol with solubilizers and auxiliary formations with an exclusive study of their properties for the development of solid dosage forms.Materials and methods. Trans-resveratrol, poloxamer 407, polysorbate 80, methyl-beta-cyclodextrin, citric and ascorbic acids, glycerin, methanol; high performance liquid chromatography, differential scanning calorimetry.Results. Physical and chemical studies of the obtained compositions of resveratrol with excipients were carried out. Excipients used: citric and ascorbic acids for all compositions, as well as glycerin for compositions with tween 80. Stability studies were carried out under conditions of «accelerated aging», as a result of which a noticeable decrease in the amount of resveratrol was found (80 % of the original). Studies of the stability of resveratrol have shown that at low pH, inherent in the stomach, its content remains practically unchanged for two days. And at pH close to neutral, the content of resveratrol is reduced to 90 % of the original amount. The obtained results indicate the feasibility of developing drugs that promote the absorption of resveratrol in the stomach and are stored at low temperatures (in the refrigerator).Conclusion. Compositions of resveratrol with solubilizers were obtained and the choice of excipients for the development of solid dosage forms was substantiated. Recommendations are given for obtaining solid dosage forms for each of the developed formulations and storage conditions are determined.

Introduction. Increasing of poorly soluble pharmaceutical substances bioavailability is one of important problems of pharmaceutical technology. Resveratrol is a plant origin polyphenol with a broad spectrum of biological effects. However, due to poor solubility and, as a result, low bioavailability, it is not promising for the development of oral drugs. Thus, today resveratrol is presented only as a biologically active substance that is component of biologically active food supplements.The objective of the research is selection of the optimal solubilizer to increase the solubility of resveratrol by determining the solubilization parameters.Materials and methods. The spectrophotometric characteristics of resveratrol were studied using three groups of solubilizers: poloxamers, polysorbates and cyclodextrins. Studies were carried out in 50 mM hydrochloric acid buffer(pH 1.2) and 50 mM phosphate buffer(pH 6.8). Spectrophotometric measurements were carried out on a spectrophotometer UV/VIS-3600 Shimadzu (Japan) in the wavelength range of 220–380 nm. The effect of solubilizers on the spectrophotometric characteristics of resveratrol was determined in buffer solutions containing the solubilizer and resveratrol in significantly less concentration of its own solubility in water. The used multiple excess of the solubilizer ensured the finding of all resveratrol in a solubilized form. During the determining parameters of solubilization, buffer solutions containing from 2 to 10 mM solubilizers were added to the obviously excess of resveratrol. The indicated amount of resveratrol ensured the presence of its precipitate in all experimentsto determine the completeness of solubilization of the studied polyphenol.Results. Based on the obtained spectrophotometric characteristics of solubilizers solutions with resveratrol, the most effective for the further development of solid dosage forms for oral administration are poloxamer 407, polysorbate 80 and modified methyl-beta-cyclodextrin, which ensure complete dissolution of resveratrol when its content in the composition with a solubilizer is about 10 %.Conclusion. Based on the data obtained on the spectrophotometric characteristics of resveratrol using solubilizers, it can be argued that it is possible to create drugs with improved solubility of the studied polyphenol. On the basis of its compositions with poloxamer 407, polysorbate 80 and modified methyl-beta-cyclodextrin, with the selection of appropriate excipients, solid dosage forms for oral intake can be developed.

Introduction. Nowadays, the development of delivery systems based on micro- and nanoparticles is being actively pursued to increase the selectivity and efficiency of photosensitizers in photodynamic therapy. Such microparticles could increase the effectiveness of the already used chemotherapeutic drugs due to their accumulation in the tumor and help to overcome the drug resistance of tumor cells.The aim of this research was to obtain microparticles based on a biocompatible block copolymer of lactic and glycolic acids with the inclusion of the photosensitizer radachlorin, magnetic nanoparticles, and perfluorodecalin and their subsequent evaluation as therapeutic agents for photodynamic therapy.Materials and methods. Microparticles were obtained using the double emulsion method, described using of electron microscopy. Evaluation of their photodynamic properties was carried out using spectrophotometry and MTTtest on cell culture.Results. Spherical microparticles with a size of less than 1 μm were obtained. The release of the active substance from microparticles occurred gradually over two weeks, and in the case of the presence of magnetic nanoparticles, the concentration of radachlorin remained practically unchanged for a month. Exposure of microparticles to the light of LED is accompanied by the formation ofsinglet oxygen. Electron microscopy indicated intracellular position of microparticlesin tumor cells. The MTT test revealed a significant inhibition of cell viability in the presence of microparticles.Conclusion. The research results allow us to consider the obtained biocompatible polymer microparticles with the inclusion of radachlorin as a depot of radachlorin for local use in photodynamic therapy of tumors.