Hard to swallow dry: kinetics and mechanism of the anhydrous thermal decomposition of acetylsalicylic acid

The methods of thermal analysis and mass spectrometry have been used to study the kinetics and mechanism of the anhydrous thermal decomposition of acetylsalicylic acid. Both thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) show that decomposition occurs in two steps. Mass-spectrometric analysis of the residue left after the first decomposition step (approximately equal to 60% mass loss) suggests that in the condensed phase, acetylsalicylic acid decomposes by first forming linear oligomers that are further converted into cyclic oligomers. Model-free isoconversional kinetic analysis of TGA traces has been used to determine global activation energies as a function of the extent of reaction. This method of analysis has also been used to make kinetic predictions of shelf life at ambient temperatures (20-40 degrees C) under anhydrous conditions for acetylsalicylic acid. Our estimate of a shelf life of 876 days (approximately equal to 2.4 years) for 5% decomposition at 30 degrees C is in good agreement with shelf lives of 2-3 years that are stamped on over-the-counter aspirin bottles. Hence, this approach can be used to systematically study the factors that determine the decomposition kinetics of aspirin and may be used for express screening of pharmaceuticals in order to identify those with desirable thermal stabilities.