Comminution and amorphisation of Diaqua-bis(Omeprazolate)-Magnesium Dihydrate: An analysis of the energies involved

Abstract

Size reduction of Diaqua-bis(Omeprazolate)-Magnesium Dihydrate (DABOMD) crystals, an active pharmaceutical ingredient (API) which inhibits gastric acid secretion and its related disorder in mammals, has been investigated using a planetary ball mill and a single ball mill. The outcome of milling shows that DABOMD undergoes prominent comminution and amorphisation processes that occur parallel to each other, with planetary ball mill causing higher amorphisation rate compared to the single ball mill. To establish a relationship between the degree of comminution and amorphisation, the energies of the planetary ball mill and the single ball mill were quantified using a collision model derived from the literature, and through tracking the milling jar with high speed-camera, respectively. In addition, energies were calculated using the Discrete Element Method (DEM) simulations of both mills. The energy obtained from the DEM simulation of the planetary ball mill is lower than the calculated energies from the literature collision model. This could be due to the fact that the collision model does not consider additional factors affecting the motion of balls, such as friction between the balls and balls and the wall. However, the energy calculated from the DEM simulation is higher than that generated from high speed video tracking of the milling jar for the single ball, since as shown by the DEM the movement pattern and the velocity magnitude of the ball is different to those of the jar, resulting in higher relative collision velocities than the jar velocity itself. Nevertheless, it was found that the planetary ball mill produces higher energy than the single ball mill which explains the difference in the amorphisation obtained in the two mills. This methodology enables quantification of the changes that arise with the milling of a solid (i.e. comminution and amorphisation) with respect to the energy level involved.