Focused-ion-beam milling: a novel approach to probing the interior of particles used for inhalation aerosols.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Heng
Desmond
D
Faculty of Pharmacy, A15, The University of Sydney, NSW 2006, Sydney, Australia.
Tang
Patricia
P
Cairney
Julie M
JM
Chan
Hak-Kim
HK
Cutler
David J
DJ
Salama
Rania
R
Yun
Jimmy
J
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D004205:Cromolyn Sodium / Q000737:chemistry; D008353:Mannitol; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D012710:Serum Albumin, Bovine / Q000648:ultrastructure; D013678:Technology, Pharmaceutical
D000336:Aerosols; D012710:Serum Albumin, Bovine; D008353:Mannitol; D004205:Cromolyn Sodium