An investigation into the effects of thermal history on the crystallisation behaviour of amorphous paracetamol

The effects of thermal history and sample preparation on the polymorphic transformation profile from amorphous paracetamol have been investigated. The crystallisation behaviour of slow and quench cooled amorphous paracetamol was studied using DSC. Quench cooled paracetamol showed a glass transition ( T g) at 25.2 °C, a single exothermic transition at 64.9 °C and an endotherm at 167.7 °C. The initial degree of crystallinity was calculated as a function of time and recrystallisation circa 20 °C below T g was demonstrated. Slow cooled material in pinholed or hermetic pans (sealed under nitrogen) showed a T g at 25.1 °C, two exothermic transitions at circa 80–85 °C and 120–130 °C followed by melting at 156.9 °C; a single exotherm at 83 °C was observed for material sealed in hermetic pans under ambient conditions. Hot stage microscopy yielded complementary information on crystal growth and transformation profile. A transformation scheme is proposed which indicates that amorphous paracetamol may transform into Form III, II or I depending on the thermal history and the gaseous environment in which recrystallisation takes place. The study has demonstrated that the thermal history and encapsulation method may profoundly influence the polymorphic forms generated from amorphous paracetamol.