Studies of thermal behavior of metoprolol tartrate

Abstract

The thermal behavior of metoprolol tartrate [(2R,3R)-2,3-dihydroxybutanedioic acid; 1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol], a β-adrenergic blocker used in the treatment of hypertension and other cardiac problems, was investigated using thermogravimetry (TG), differential thermal analysis (DTA), differential scanning calorimetry (DSC), evolved gas analysis by thermogravimetry coupled with infrared spectroscopy (TG-FTIR), hot-stage microscopy and high-performance liquid chromatography coupled with mass spectrometry (HPLC–MS). TG/DTA and TG-FTIR showed that metoprolol melts at 123.3 °C and 124.2 (N2 and air, respectively) and started decomposing at 155.4 °C (in N2) and 152.6 °C (in air) in two steps of mass loss with the release of carbon monoxide, carbon dioxide and water from the decomposition of tartaric acid in the first step and carbon dioxide, ammonia, dimethyl ether, 1-ethoxy-4-methylbenzene and isopropyl isocyanate in the second step. DSC curves demonstrated that the sample melts at 121.7 °C, quite similar to that observed in DTA, with no recrystallization on cooling. Hot-stage microscopy allowed seeing the melting process of metoprolol, which appeared in a temperature similar to that observed in the other thermal analytical techniques. HPLC–MS analysis permitted characterizing some solid intermediates of drug degradation, indicating that probably there is an intermolecular interaction between the molecules during the decomposition, creating larger molecules. Based on these results, a tentative mechanism for metoprolol tartrate thermal decomposition was proposed.