Abstract
The purpose of the following research was to improve the original Celsior solution in order to obtain a higher degree of stability and effectiveness. The solution was modified by the addition of selected antioxidants such as vitamin C, cysteine, and fumaric acid in the following concentrations: 0.1, 0.3, and 0.5 mmol/l. The solution’s stability was estimated using an accelerated stability test based on changes in histidine concentrations in the solution using Pauly’s method for determining concentrations. Elevated temperatures, the factor accelerating substances’ decomposition reaction rate, were used in the tests. The research was conducted at four temperatures at intervals of 10°C: 60 ± 0.2°C, 70 ± 0.2°C, 80 ± 0.2°C, and 90 ± 0.2°C. It was stated that the studied substances’ decomposition occurred in accordance with the equation for first-order reactions. The function of the logarithmic concentration (log%C) over time was revealed to be rectilinear. This dependence was used to determine the kinetics of decomposition reaction rate parameters (the rate constant of decomposition k, activation energy E a, and frequency factor A). On the basis of these parameters, the stability of the modified solution was estimated at +5°C. The results obtained show that the proposed antioxidants have a significant effect on lengthening the Celsior solution’s stability. The best results were reached when combining two antioxidants: vitamin C and cysteine in 0.5 mmol/l concentrations. As a result, the Celsior solution’s stability was lengthened from 22 to 299 days, which is 13.5 times. Vitamin C at a concentration of 0.5 mmol/l increased the solution’s stability by 5.2 times (t 90 = 115 days), cysteine at a concentration of 0.5 mmol/l caused a 4.4 times stability increase (t 90 = 96 days), and fumaric acid at a concentration of 0.5 mmol/l extended the stability by 2.1 times (t 90 = 48 days) in relation to the original solution.
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This study was funded by the State Committee for Scientific Research, Warsaw, Poland (grant PBZ-KBN-048/PO5/2001).
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Ostróżka-Cieślik, A., Dolińska, B. & Ryszka, F. Influence of the Selected Antioxidants on the Stability of the Celsior Solution Used for Perfusion and Organ Preservation Purposes. AAPS PharmSciTech 10, 468–475 (2009). https://doi.org/10.1208/s12249-009-9232-3
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DOI: https://doi.org/10.1208/s12249-009-9232-3