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

Mansour Latreche (1) , Jean-François Willart (1) , Mathieu Guerain (1) , Alain Hédoux (1) , Florence Danede (1)

1 UMET - Unité Matériaux et Transformations - UMR 8207

This paper 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 non-milled material. This possibility was clearly demonstrated to result from crystalline micro strains 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.

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

Domaines: Matière Molle [cond-mat.soft]; Pharmacie galénique

Mansour Latreche, Jean-François Willart, Mathieu Guerain, Alain Hédoux, Florence Danede. Using Milling to Explore Physical States: The Amorphous and Polymorphic Forms of Sulindac. Journal of Pharmaceutical Sciences, 2019, 108 (8), pp.2635-2642. ⟨10.1016/j.xphs.2019.03.017⟩. ⟨hal-02363256⟩