The use of high-speed differential scanning calorimetry (Hyper-DSC™) in the study of pharmaceutical polymorphs

The thermal properties of two polymorphs (A and C) of a Merck development compound were studied using high-speed differential scanning calorimetry (Hyper-DSC™). The utility of this novel technique as a fast analytical tool for studying the polymorphic behaviour of metastable polymorphs has previously been demonstrated successfully for Carbamazepine. Accelerated heating rates can alter the kinetics of the melting transition of metastable polymorphs such that concurrent exothermic recrystallisation is inhibited. Here it is demonstrated that at heating rates of 400 °C/min concurrent recrystallisation of Polymorph A of the Merck development compound is inhibited allowing the enthalpy of fusion for the lower melting Polymorph C to be determined. The utility of the technique as a qualitative tool to detect the presence of polymorphic impurities was confirmed for levels much lower than 10% (w/w). However, seeding effects consistent with those reported previously for Carbamazepine were also observed for this structurally distinct molecule limiting the utility of the technique for accurate quantification of low levels of polymorphic impurities.