DSC and spectroscopic studies of disulfiram radiostability in the solid state |
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Authors: | Barbara Marciniec Katarzyna Dettlaff Marek Naskrent Zuzanna Pietralik Maciej Kozak |
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Institution: | (1) Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland;(2) Department of Medical Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland;(3) Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland; |
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Abstract: | The effect of ionising radiation on the physico-chemical properties of disulfiram (Antabuse, Esperal, bisdiethylthiocarbamoil
disulphide) has been studied by DSC, FTIR, EPR, MS, TLC and HPLC. Sterilisation was carried out in the solid state, at room
temperature and normal air humidity using the electron beam of 9.96 Mev from accelerator. All the measurements were made simultaneously
for the irradiated and nonirradiated substance. It has been found that the drug studied in solid phase when subjected to an
electron beam corresponding to the irradiation in the doses 10–100 kGy shows the presence of free radicals (EPR), and a change
in colour from white to pale green-grey that disappears after solution in water or methanol. After the irradiation with the
dose of 100 kGy, its melting point and enthalpy slightly decreased. Also the content of the active substance decreases (HPLC
−1.5%, UV −3.6%, iodometric titration method −2.7%) and trace amounts of the radiolysis products appear (HPLC). The substance
irradiated with the doses 10–50 kGy does not show changes in the melting point, in the content and presence of the radiolysis
products. The EPR results have shown that free radicals disappear after about a year and the discolouring disappears with
them. The results of this study have shown that disulfiram can be subjected to sterilisation by irradiation with no deterioration
of its physico-chemical properties, but a long time of storage needed to remove free radicals and discolouration questions
the economic justification for this type of sterilisation. |
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