Tailoring the flow properties of inhaled micronized drug powders by atomic and molecular layer deposition

For dry powder inhaled formulations, good flow behaviour is vital in re-dispersing the powder. However, inhaled drug powders with a particle size below 10 mu m are classified as highly cohesive materials with poor flow characteristics. Here we demonstrate how to alter the flow properties of micronized budesonide powders by depositing different materials (organic, inorganic, and hybrid organic-inorganic) in the forms of nanoscale films onto the drug particles using atomic/molecular layer deposition (ALD/MLD) coatings. The angle of repose (static) and pneumatic delivery measurements were performed to access the flow characteristics. The flowability can be effectively improved with the growth of inorganic nanofilm (SiO2, TiO2, or Al2O3) via ALD and hybrid nanofilm (titanicone) via combined ALD-MLD coating. This improvement is reflected by the decrease in the angle of repose and minimum pick-up velocity (Upu), as well as promoting the pneumatic delivery of a much larger amount of drug powders after ALD or hybrid coating. In contrast, the organic PET coated budesonide via MLD exhibits comparable poor flow characteristics as the uncoated budesonide. Rather than being transported in individual particles, the uncoated or PET-coated budesonide powders are pneumatically delivered in form of complex clusters with a size of over 500 mu m, whereas the ALD budesonide is dispersed in form of small agglomerates (<100 mu m). Despite the difference in agglomerate size, entraining behaviors of all samples agree well with the prediction of Kalman's pick-up Zone I correlation. The inorganic nanofilm deposited via ALD alters the surface chemistry to reduce the inter-particle forces measured by atomic force microscopy, giving rise to an improved drug delivery performance. Nanoscale surface modification of dry powder particles has good potential for inhaled drug delivery enhancement.