Thermal degradation mechanism for citalopram and escitalopram

Citalopram, [(R,S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile] hydrobromide and its S-isomer, escitalopram oxalate, were analyzed regarding thermal degradation by TG/DTG–DTA, DSC, hot-stage microscopy and coupled TG-FTIR techniques. Citalopram presented a decomposition in a single step after melting at 189.3 °C (ΔHfus= 94.4 J g−1), without evidences of crystallization on cooling. Thermal techniques results combined with those from evolved gas analysis suggested decomposition via HBr, dimethylamine and fluorobenzene. Escitalopram presented a thermal degradation that started with the decomposition of the counter ion, after melting at 158.3 °C (ΔHfus= 106.2 J g−1), without evidences of crystallization on cooling followed by the release of dimethylamine and fluorobenzene. GC–MS of the residues confirmed the observations from the thermal analysis, but revealed several intermediates in the degradation of the racemate, probably due to the mixture of isomers. Differences in thermal behavior were attributed to differences in structure and counter ions. A tentative mechanism for their thermal behavior is proposed in both cases.