Evolved gas analysis during thermal degradation of salbutamol sulphate

Crystalline Salbutamol sulphate (SS) is a common β2-agonist used in dry powder inhalers for the treatment of asthma. The solid-state characteristics of SS are import since they govern the stability and thus efficacy of the drug when incorporated into an inhalation medicine. Previous studies have investigated the thermal properties of SS and the complex array of thermal events have been attributed a mixture of melting and/or degradation mechanisms. In order to ascertain the exact thermal transformation processes that SS undergoes we utilised a combination of differential scanning calorimetry coupled with quadrupole mass spectrometry and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy over the temperature range 25–500 °C. Based on the coupled thermal analysis data we proposed that SS undergoes a multi-step degradation mechanism in which the molecule dehydrates loosing water initially, followed by the break up of the secondary amine group and lastly formation of sulphur dioxide. When used in conjunction, the analytical techniques offered significant advantages over the use of thermal analysis alone, offering a better understanding of the transformations occurring to SS following heating.