Assessment of amorphization behavior of a drug during co-grinding with an amino acid by discrete element method simulation

The amorphization of indomethacin (IMC) with cystine (Cys2) was studied by discrete element method (DEM) simulations and principal component analysis (PCA). X-ray powder diffraction (XRPD) analysis suggested that the conversion of crystalline IMC to amorphous state was accelerated by co-grinding with Cys2. XRPD spectra about amorphization of IMC with Cys2 were analyzed by PCA. PCA results suggest that IMC/Cys2 system undergoes two-phase amorphization, as indicated by the 2nd PC score, and that the change in phase depends on the total frictional energy calculated by DEM simulations. Electron spin resonance result revealed that the radical from Cys2 may be related to the amorphized progression of IMC. (C) 2018 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.