Bessarabov V. Technologies of complex use of polymer composite materials in the production of geriatric drugs

The dissertation is devoted to solving the problem of creating a system of methods for implementing the principles of economical production on the example of technologies for the use of polymer composite materials at all stages of the life cycle of geriatric drugs, from pharmaceutical development to production, toxic waste disposal and sanitary and fire regulations in production facilities. Technological processes for obtaining polymeric composite materials in the form of solid dispersed systems of the flavonoid hesperidin have been developed, which has significantly increased its bioavailability. For the first time developed the composition and method of obtaining a geriatric pharmaceutical composition based on a solid dispersed system of hesperidin with pharmaceutically acceptable polymers and surfactants with improved parameters of specific pleiotropic pharmacological activity and bioavailability. The relationship between the molecular weight of polyvinylpyrrolidone in the polymeric TDS of hesperidin and its solubility in water has been established, which is probably due to the number of functional groups in the polymer molecule that participate in the formation of hydrogen bonds. The maximum value of increasing the solubility of hesperidin is observed in the system with polyvinylpyrrolidone K-25 and cetylpyridinium chloride - 42.7 times. The effect of temperature on water solubility Hes as a part of polymeric TDS is shown. The maximum value of the increase in solubility is observed at a temperature of 40 ± 0.5 °C - 43.3 times in the system with polyvinylpyrrolidone K-25 and cetylpyridinium chloride. Thermodynamic parameters of formation of polymeric TDS of hesperidin are calculated. It is shown that the solubilization of hesperidin in the presence of a polymer occurs under favorable conditions. Increasing the polymer concentration and the reaction temperature contribute to a better reaction of the formation of intermolecular complexes. It is established that the process of formation of intermolecular complexes has a spontaneous character at selected temperatures and is endothermic. It is shown that the formation of complexes between hesperidin and excipients occurs during the destruction of the aqueous solvate shell of molecules. The solubility parameters of polymeric TDS hesperidin at different pH values were studied, which indicate that the neutral environment of the large intestine in the human body will be the target site of release of Hes from TDS. The effect of human serum on Hes and its intermolecular complexes with high molecular weight and surfactants, which suggest a better preservation of the biological activity of hesperidin in the polymeric TDS Hes compared with pure Hes. In addition, it was found that Hes, which is part of the complex with high molecular weight polymer and surfactants, is less destructive to serum enzymes than Hes in pure form. A study of the chemical compatibility of the components and the stability of the polymeric TDS of hesperidin, which indicate slight deviations of the quantitative content of Hes in the TDS during the observation period, compared with the initial values. Using the FTIR spectroscopy method, the absence of chemical interactions (chemical compatibility) of the components of polymeric TDS hesperidin and the stability of the system under test conditions were proved. It is concluded that in the development of the composition of the pharmaceutical composition based on polymeric TDS hesperidin carried out the optimal selection of excipients and technology for the manufacture of TDS. Optical microscopy has shown that the obtained polymeric TDS of hesperidin has an amorphous structure, the particles of which are isometric, which will promote better dissolution due to the larger surface area of the particles. The formation of PVP K-25 + Hes polymer complexes, mainly due to hydrogen bonds, has been proved using FTIR spectroscopy. The complexes formed are characterized by an increase in the number of hydrogen bonds by more than a third compared to the components of the polymer composite system. For the first time it was established that polymeric TDS of hesperidin inhibits butyrylcholinesterase of human serum by a mixed (partial) mechanism. TDS of hesperidin has been shown to be almost 19 times more effective as a serum butyrylcholinesterase inhibitor than hesperidin (IC50). Technological processes of creation of in situ highly effective systems of decontamination of residues of organophosphorus active pharmaceutical ingredients in the technological equipment of pharmaceutical enterprises are investigated. Technological approaches to the creation of highly effective intumescent coatings with anti-mold properties are shown.