Abstract
Changes of the chemical structure and free radicals formation in aminoglycoside antibiotics during sterilization at temperatures 160°C, 170°C, and 180°C according to the pharmacological norms were studied. EPR and DRIFT spectroscopy were applied as experimental methods. It was demonstrated that free radicals are formed in streptomycin, gentamicin, neomycin, sisomicin, paromomycin, and tobramycin during thermal sterilization. Complex free radicals system with the complex shape of EPR spectra characterized the tested samples. Mainly oxygen free radicals exist in the tested heated antibiotics. The EPR lines of the analyzed antibiotics are homogeneously broadened. Fast spin-lattice relaxation processes exist in the examined sterilized aminoglycoside antibiotics. Free radicals concentrations in the aminoglycoside antibiotics depend on the temperature and time of sterilization. The highest free radicals concentrations characterize thermally sterilized sisomicin. Streptomycin, gentamicin, neomycin, paromomycin, and tobramycin may be sterilized at temperatures 160°C, 170°C and 180°C. Sisomicin should be sterilized at temperature 180°C. Free radicals concentration changes during storage of the examined antibiotics, and probably interactions with oxygen molecules may be responsible for this effect. DRIFT studies shown that sterilization conditions, the temperature and the presence of oxygen, causes only small changes in the chemical structure of aminoglycoside antibiotics by alteration of the functional groups. EPR and DRIFT methods are proposed to optimization of the thermal sterilization process of drugs and conditions of their storage.
Highlights
Process of sterilization is preformed to kill microorganisms in drugs and to rise the safety of the pharmacotherapy [1,2,3]
The Electron Paramagnetic Resonance (EPR) spectra of streptomycin (a), gentamicin (b), neomycin (c), sisomicin (d), paromomycin (e), and tobramycin (f), sterilized at 160oC (120 minutes), 170°C (60 minutes), and 180oC (30 minutes) measured with microwave power of 2.2 mW at room temperature 20 minutes after sterilization are presented in figure 2
Free radicals are formed in streptomycin, gentamicin, neomycin, sisomicin, paromomycin, and tobramycin in the process of thermal sterilization at temperatures 160°C, 170°C and 180°C
Summary
Process of sterilization is preformed to kill microorganisms in drugs and to rise the safety of the pharmacotherapy [1,2,3]. The parameters of the thermal sterilization are fitted to the resistance of microorganisms and they are regulated by the norms [2,3]. Thermal sterilization may be done for the drugs resistant to temperature interactions. Thermal sterilization should not produce the high amounts of free radicals in the drugs and should not considerably change their chemical structure. Free radicals as the molecules containing unpaired electrons may be responsible for toxic effects in organism [8]. Both free radicals and the changed chemical units in the drugs may decrease their pharmaceutical effectiveness in human tissues
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