Using Milling to Explore Physical States: The Amorphous and Polymorphic Forms of Sulindac

Abstract

This article shows how milling can be used to explore the phase diagram of pharmaceuticals. This process has been applied to sulindac. A short milling has been found to trigger a polymorphic transformation between form II and form I upon heating which is not seen in the nonmilled material. This possibility was clearly demonstrated to result from crystalline microstrains induced by the mechanical shocks. A long milling has been found to induce a total amorphization of the material. Moreover, the amorphous fraction produced during milling appears to have a complex recrystallization upon heating which depends on the milling time. The investigations have been mainly performed by differential scanning calorimetry and powder X-ray diffraction.

Keywords: Differential Scanning Calorimetry (DSC); X-ray Powder Diffraction (XRD); glass; glass transition(s); materials science; milling; phase transformation(s); phase transition(s); polymorphism; solid-state stability.