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 beta relaxations typical of glasses in the milled compound. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:15701577, 2012