Investigation of Thermal Properties of Itraconazole at Ultra-Fast Rates*

The thermal behavior of itraconazole (ITZ) was studied using a conventional differential scanning calorimeter (DSC) and a flash differential scanning calorimetry (Flash DSC) over five decades of cooling rates. Itraconazole forms a smectic glass and shows two endothermic liquid crystal transitions located at 74 and 90 °C at all cooling rates in DSC. On the other hand, in the Flash DSC, the glass that is formed can have smectic order for the lowest cooling rates, nematic order at intermediate cooling rates, and no ordering (i.e., an isotropic glass is formed) at the highest cooling rates of 1000 K/s. The T_g values obtained in conventional and Flash DSC are similar at comparable cooling rates and can be described by the WLF equation over five decades of cooling rate. No discernible change in the T_g versus cooling rate relationship is evident as different glasses are formed, suggesting that differences in T_g for the three glasses is solely attributable to the different cooling rates and not due to the difference in structures. Additionally, the kinetics of the liquid crystal transformations and the kinetics of structural recovery are followed by annealing at different temperatures ranging from -30 to 92 C.