Study of solid-state degradation of prochlorperazine and promethazine

Prochlorperazine (PCP) and promethazine (PMT) are dopamine (D2) receptor antagonists with a phenothiazinic structure that used nowadays mainly for their antiemetic properties, including for the pre- and postoperative setting. In this paper, the thermal behavior of PCP and PMT was studied, including a complete kinetic analysis for the evaluation of the degradation process in heterogenous media. Samples were analyzed using Fourier transform infrared spectroscopy, thermogravimetric analysis (TG/DTG/HF) and a preliminary kinetic analysis using the ASTM E698 kinetic method, the obtained data being later completed with an in-depth kinetic analysis according to ICTAC 2000 protocol, using the isoconversional methods of Friedman, Ozawa–Flynn–Wall, Kissinger–Akahira–Sunose, respectively, the modified nonparametric kinetics method, the latter allowing the determination of the kinetic triplet without using any approximation, but as well the separation of parallel reaction that occurs at decomposition. The results confirmed that PCP dimaleate has a better stability in comparison with PMT hydrochloride, in terms of apparent energy of activation, probably due to solid-state structure of solid and the contribution of intermolecular bondings.