The mechanism and the kinetics of thermal decomposition of brivudine / 中国药学杂志

ABSTRACT

OBJECTIVE: To understand the thermal stability, mechanism and kinetics of thermal decomposition of brivudine (BVDU). METHODS: The thermal decomposition process of BVDU was studied by means of thermogravimetry (TG), differential scanning calorimetry (DSC), and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy (TGA-FTIR). The infrared spectra of BVDU, its gaseous products and remainders of thermal decomposition at various temperatures were determined. The molecular bond orders were calculated by GAMESS program of quantum chemistry, and the mechanism of the thermal decomposition of BVDU is discussed. The parameters of thermal decomposition kinetics, such as activation energy Es and pre-exponential factor A, were obtained by using Ozawa method. The prospective lifetime of BVDU was estimated by using Dakin equation. RESULTS: The thermal decomposition of BVDU is a three-stage process. Disconnection of the C-N bond between thymine ring and tetrahydrofuran ring occurrs in the initial step of the decomposition. In nitrogen atmosphere, the average Ea and A of the first stage are 171.1 kJ·mol-1 and 2.630×10 min-1 respectively. In air atmosphere, the corresponding Ea and A are 152.9 kJ·mol-1 and 1.660×10 min-1 respectively. CONCLUSION: The thermal property of BVDU is quite stable in the routine temperature.