Reaction kinetics of solid-state cyclization of enalapril maleate investigated by isothermal FT-IR microscopic system

To investigate the reaction kinetics of the solid-state degradation process of enalapril maleate, a Fourier transform infrared microspectroscope equip ped with thermal analyzer (thermal FT-IR microscopic system) was used. The isothermal stability study was conducted at 120-130 degreesC for 1-2 h and changes in the three-dimensional plots of the TR spectra of enalapril malea te with respect to heating time were observed. The study indicates that the bands at 1649, 1728, and 1751 cm(-1) assigned to intact enalapril maleate gradually reduced in peak intensity with heating time. However, the peak in tensities at 1672 and 1738 cm(-1) (due to enalapril diketopiperazine (DKP) formation) and at 3250 cm(-1) (corresponding to water formation) gradually increased with heating time. The solid-state diketopiperazine formation and the degradation process of enalapril maleate via intramolecular cyclizatio n were found to be simultaneous. The isothermal decomposition curves were s igmoidal and were characterized by induction and acceleration periods, indi cating the presence of autocatalytic solid-state decompositions, Moreover, the power-law equation (n=1/4) was found to provide the best fit to the kin etics of decomposition. This isothermal FT-IR microscopic system was easily used to investigate the degradation of enalapril maleate and the concomita nt formation of DKP, The solid-state reaction of enalapril maleate required an activation energy of 195 +/- 12 kJ/mol to undergo the processes of deco mposition and intramolecular cyclization.