Effect of headspace gas on nucleation of amorphous paracetamol

In this paper, the effect of the gaseous environment on recrystallization of amorphous paracetamol was investigated. The experiments were conducted with a headspace gas consisting of dry air, dry carbon dioxide, dry nitrogen and humid air in four temperatures ranging from 5 °C below onset of Tg to 5 °C above onset of Tg. The recrystallization was monitored using Raman spectroscopy and subsequent multivariate analysis. In temperatures below onset of Tg, the presence of oxygen delayed the onset of recrystallization, with an increasing delay with lower temperature. When comparing samples exposed to dry headspace gases, the crystallization was fastest below onset of Tg when exposed to nitrogen. Being an inert gas, nitrogen did not seem to interfere with the molecules allowing them to freely find their inherent arrangement, whereas the presence of oxygen delayed the formation of stabile nuclei. Above onset of Tg, no differences in onset of crystallization was detected between dry gas atmospheres. Amorphous paracetamol crystallized to form II in all measurements and the samples did not reach full crystallinity within the duration of the experiments. The results show that the headspace gas has an effect on nucleation in the amorphous sample.