Micro-particle corrugation, adhesion and inhalation aerosol efficiency

Atomic force microscopy (AFM) was used to evaluate the particle adhesion and surface morphology of engineered particles for dry powder inhaler (DPI) respiratory therapy to gain a greater understanding of interparticle forces and the aerosolisation process. A series of spherical model drug particles of bovine serum albumin (BSA) was prepared with different degrees of surface corrugation. The particles were evaluated in terms of particle size (laser diffraction) and microscopic morphology (scanning electron microscopy). Conventional tapping mode AFM was used to evaluate the nanoscopic morphology and derive specific roughness parameters, while AFM colloid probe microscopy was used to directly measure the interaction of functionalised probes. The physical characterisation and AFM measurements were evaluated in terms of in vitro aerosolisation performance, using a conventional Rotahaler® DPI and multistage liquid impinger. A direct relationship between the root mean square roughness, particle adhesion and in vitro aerosol performance (measured as fine particle fraction, FPF) was observed suggesting that as the degree of corrugation increased, particle adhesion was reduced which, resulted in a concomitant increase in FPF. This study demonstrates that AFM may be used to predict the aerosolisation performance micron sized particles for inhalation based on their morphological properties.