The use of atomic force microscopy to study the conditioning of micronised budesonide

Patent literature describes “conditioning” techniques which employ organic vapours to recrystallise amorphous regions in micronised particles, with the aim of improving their processability and physico-chemical stability. This report describes a preliminary study investigating the efficacy of PhaseImaging™ atomic force microscopy (AFM) for the investigation of such processes. AFM phase images demonstrated variation in mechanical properties across the surface of milled budesonide particles, which diminished upon exposure to ethanol vapour. No variation was seen in phase images of unmilled budesonide. Dynamic vapour sorption confirmed the presence amorphous material in the milled sample and its subsequent recrystallisation following exposure to ethanol vapour under the same conditions as those used in the AFM experiment. It was therefore hypothesised that variation in the phase images indicated the presence of amorphous regions which were subsequently conditioned. PhaseImaging™ AFM may therefore be a useful method for the study of conditioning techniques, enabling the efficacy and kinetics of the process to be observed.