Surface Stability of Processed Particles

The uncontrollable nature of secondary processing (e.g. micronisation, milling) of active pharmaceutical ingredients has been shown to lead to significant inter and intra batch variations in formulation performance and the potential source of instability within powder based formulations. The shear forces applied inevitably lead to localised formation of amorphous disorder on the surfaces of the particles. Although the concentration may be low, for high surface area to volume particles it may significantly affect their physico-chemical properties.

To investigate their possible effects, we have utilised the AFM in its conventional imaging mode together with an auxiliary phase imaging technique to elucidate variations in the physico-mechanical properties of mechanical processed particles. This novel approach has provided direct characterisation of surface induced disorder of processed particle and real-time visualisation of the surface stability induced by variations in temperature and/or moisture (see Figures below).

Low %RH..................................................High%RH

Moisture induced surface recrystallisation of a micronised particle