The article studies the mechanism of thermal decomposition of two drugs from the group of isoxazolidines D-cycloserine, and terizidone, potentially exposed to the action of elevated temperatures in production (preparation and drying stages). As a result of series of the analytical experiments on the study of solid products of samples thermal decomposition by IR spectroscopy, including with the participation of a comparative sample (more thermally stable nootropic drug fonturacetam), it was established that the antibiotics D-cycloserine and terizidone containing in their molecular formula a five-membered heterocycle with the [–C–O–N–] group (absorption band in the area of 1461 cm–1) have low thermal stability associated with the ease of breaking N–O bond. It is noted that at the maximum degrees of decay, the specified absorption band weakened until it completely disappeared. The obtained results on thermal decomposition, apparently, can be interpolated to all the substances having specified heterocycle in the structure, which is explosiphoric. Before launching into production, when modeling substances with the specified pharmacological properties, it is required, if possible, to avoid structures with a similar heterocycle with a choice of more heat-resistant analogues that are not inferior in efficiency. Such solutions to reduce fire hazard at the stage of development of technological processes seem to be the most efficient. The study results confirming the propensity of the studied compounds to thermal decomposition at relatively low temperatures contributed to the creation of a safe technological process, storage and transportation conditions at the place of production of FGUP «GNTs «NIOPIK».
2. On the approval of the Program of fundamental scientific studies in the Russian Federation for the long term (2021–2030): Decree of the Government of the Russian Federation of December 31, 2020 № 3684-r. Available at: https://base.garant.ru/400170256/ (accessed: October 1, 2021). (In Russ.).
3. Antibiotic market in Russia of 2020: operational data of 2012–2021, and the forecast up to 2025. Available at: https://marketing.rbc.ru/research/33173/ (accessed: October 1, 2021). (In Russ.).
4. LoBue P. Extensively drug-resistant tuberculosis. Current Opinion in Infectious Diseases. 2009. Vol. 22. Iss. 2. pp. 167–173. DOI: 10.1097/QCO.0b013e3283229fab
5. Chauhan A., Kumar M., Kumar A., Kanchan K. Comprehensive review on mechanism of action, resistance and evolution of antimycobacterial drugs. Life Sciences. 2021. Vol. 274. DOI: 10.1016/j.lfs.2021.119301
6. Court R., Centner C.M., Chirehwa M., Wiesner L., Denti P., de Vries N., Harding J., Gumbo T., Maartens G., McIlleron H. Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis. International Journal of Infectious Diseases. 2021. Vol. 105. pp. 688–694. DOI: 10.1016/j.ijid.2021.03.001
7. Diel R., Sotgiu G., Andres S., Hillemann D., Maurer F.P. Cost of multidrug resistant tuberculosis in Germany — An update. International Journal of Infectious Diseases. 2020. Vol. 103. pp. 102–109. DOI: 10.1016/j.ijid.2020.10.084
8. Beschastnov M.V. Industrial explosions: assessment and prevention. Moscow: Khimiya, 1991. 431 p. (In Russ.).
9. Khyng D.T., Vasin A.Ya., Shushpanov A.N., Gadzhiev G.G. Thermal Decomposition of Terizidone. Bezopasnost v tekhnosfere: sb. st. (Safety in the technosphere: collected papers). Izhevsk: Udmurtskiy universitet, 2021. pp. 80–86. (In Russ.).
10. Chan K.V.F., Fung L., Sallivan R., Erdman P.E., Merkurio F. Protein-targeted compounds, their compositions, methods, and applications. Patent RU 2694895 C2. Applied: May 18, 2016. Published: July 18, 2019. Bulletin № 20. (In Russ.).
11. Kuehl F.A., Wolf F.J., Trenner N.R., Peck R.L., Buhs R.P., Howe E., Putter I., Hunnewell B.D., Ormond R., Downing G., Lyons J.E., Newstead E., Chaiet L., Folkers K. D-4-amino-3-isoxazolidone, a new antibiotic. Journal of the American Chemical Society. 1955. Vol. 77. № 8. pp. 2344–2345. DOI: 10.1021/ac60109a012
12. Vasin A.Ya., Do T.Kh., Gadzhiev G.G., Shushpanov A.N., Protasova A.K. Fire and Explosion Hazard of D-Cycloserine, Terizidone and their Intermediate Synthesis Product. Khimicheskaya promyshlennost segodnya = Chemical Industry Today. 2021. № 1. pp. 28–33. (In Russ.).
13. Vasin A.Ya., Do T.Kh., Gadzhiev G.G., Shushpanov A.N., Protasova A.K. Thermal analysis of the medicinal product terizidone. Sovremennye pozharobezopasnye materialy i tekhnologii: sb. materialov IV Mezhdunar. nauch.-prakt. konf., posvyashchennoy 30-y godovshchine MChS Rossii (Modern fireproof materials and technologies: collection of materials of the Sixth International Scientific-Practical Conference Dedicated to the 30th anniversary of the EMERCOM of Russia). Ivanovo: FGBOU VO Ivanovskaya pozharno-spasatelnaya akademiya GPS MChS Rossii, 2020. pp. 40–43. (In Russ.).
14. Kazantinova M.M., Shushpanov A.N., Vasin A.Ya., Do T.Kh. Fire and Explosion Hazard of the Drug Phenylpiracetam. Tekhnosfernaya bezopasnost Baykalskogo regiona: materialy Mezhdunar. nauch.-prakt. konf. (Technosphere safety of Baikal region: materials of the International Scientific-Practical Conference). Chita: Zabaykalskiy gosudarstvennyy universitet, 2019. pp. 29–37. (In Russ.).
