Focused-ion-beam milling: A novel approach to probing the interior of particles used for inhalation aerosols

The current study aimed to examine the pharmaceutical applications of the focused-ion-beam (FIB) in the inhalation aerosol field, particularly to particle porosity determination (i.e. percentage of particles having a porous interior). The interior of various spray dried particles (bovine serum albumin (BSA) with different degrees of surface corrugation, mannitol, disodium cromoglycate and sodium chloride) was investigated via FIB milling at customized conditions, followed by viewing under a high resolution field-emission scanning electron microscope. Two sets of ten particles for each sample were examined. For the spray-dried BSA particles, a decrease in particle porosity (from 50 to 0%) was observed with increasing particle surface corrugation. Spray-dried mannitol, disodium cromoglycate and sodium chloride particles were determined to be 90-100%, 0-10% and 0% porous, respectively. The porosity in the BSA and mannitol particles thus should be considered for the aerodynamic behaviour of these particles. The FIB technology represents a novel approach useful for probing the interior of particles linking to the aerosol properties of the powder. Suitable milling protocols have been developed which can be adapted to study other similar particles.