Solid-State Vitrification of Crystalline Griseofulvin by Mechanical Milling

The thermodynamic, dynamic, and structural changes of crystalline griseofulvin upon high-energy ball milling at room temperature have been studied. The investigations have been performed by differential scanning calorimetry (DSC), dielectric relaxation spectroscopy, and powder X-ray diffraction. The results indicate that this compound undergoes a direct crystal-to-glass transformation upon milling, whereas no glass transition can be clearly detected upon heating because of the exceptional sub-glass transition temperature (Tg) recrystallization of the milled sample. This intrinsic difficulty for characterizing the glassy state has been overcome using three independent strategies: (i) comparison of the evolutions upon milling of both the crystalline powder and the quenched liquid, (ii) use of fast DSC to delay the recrystallization event, and (iii) search for dielectric β relaxations typical of glasses in the milled compound.