Solid-State Amorphization of Linaprazan by Mechanical Milling and Evidence of Polymorphism

In this paper, we study the thermodynamic and structural changes of crystalline linaprazan (a proton pump inhibitor) upon high-energy ball milling at room temperature. The investigations have been performed by differential scanning calorimetry and powder X-ray diffraction. The results indicate that this drug undergoes a direct crystal-to-glass transformation upon milling. Moreover, upon heating, the amorphous material obtained by milling is shown to recrystallize toward two different polymorphs that appear to form a monotropic set. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2214–2220, 2013