Isoconversional approach for non-isothermal decomposition of un-irradiated and photon-irradiated 5-fluorouracil

• Published in: Journal of pharmaceutical and biomedical analysis 2017-10, Vol.145, p.509-516
• Main Authors: Mohamed, Hala Sh, Dahy, AbdelRahman A., Mahfouz, Refaat M.
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Antineoplastic Agents; Fluorouracil - chemistry; Humans; Isoconversional method; Kinetics; Non-isothermal decomposition; Photon-irradiation
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2017.05.027

[Display omitted] 5-Fluorouracil (5-FU) •Non-isothermal decomposition of un-irradiated and gamma-irradiated 5-FU samples were studied in static air.•The decomposition proceeds in two overlapped steps in the range of 270–360°C.•No major changes were observed in the thermal behavior as a result of gamma-irradiation.•The decomposition is controlled by A3 and A4 models for un-irradiated and by A2 for photon-irradiated 5-FU samples. Kinetic analysis for the non-isothermal decomposition of un-irradiated and photon-beam-irradiated 5-fluorouracil (5-FU) as anti-cancer drug, was carried out in static air. Thermal decomposition of 5-FU proceeds in two steps. One minor step in the temperature range of (270–283°C) followed by the major step in the temperature range of (285–360°C). The non-isothermal data for un-irradiated and photon-irradiated 5-FU were analyzed using linear (Tang) and non-linear (Vyazovkin) isoconversional methods. The results of the application of these free models on the present kinetic data showed quite a dependence of the activation energy on the extent of conversion. For un-irradiated 5-FU, the non-isothermal data analysis indicates that the decomposition is generally described by A3 and A4 modeles for the minor and major decomposition steps, respectively. For a photon-irradiated sample of 5-FU with total absorbed dose of 10Gy, the decomposition is controlled by A2 model throughout the coversion range. The activation energies calculated in case of photon-irradiated 5-FU were found to be lower compared to the values obtained from the thermal decomposition of the un-irradiated sample probably due to the formation of additional nucleation sites created by a photon-irradiation. The decomposition path was investigated by intrinsic reaction coordinate (IRC) at the B3LYP/6-311++G(d,p) level of DFT. Two transition states were involved in the process by homolytic rupture of NH bond and ring secession, respectively.