Improving Dry Powder Inhaler Performance by Surface Roughening of Lactose Carrier Particles.

Abstract

This study investigated the impact of macro-scale carrier surface roughness on the performance of dry powder inhaler (DPI) formulations. Fluid-bed processing and roller compaction were explored as processing methods to increase the surface roughness (Ra) of lactose carrier particles. DPI formulations containing either (a) different concentrations of fine lactose at a fixed concentration of micronized drug (isoniazid) or (b) various concentrations of drug in the absence of fine lactose were prepared. The fine particle fraction (FPF) and aerodynamic particle size of micronized drug of all formulations were determined using the Next Generation Impactor. Fluid-bed processing resulted in a modest increase in the Ra from 562 to 907nm while roller compaction led to significant increases in Ra > 1300nm. The roller compacted carriers exhibited FPF > 35%, which were twice that of the smoothest carriers. The addition of up to 5%, w/w of fine lactose improved the FPF of smoother carriers by 60-200% whereas only < 30% increase was observed in the rough carriers. Analysis of the FPF in tandem with shifts in the mass median aerodynamic diameter of dispersed drug suggested that the finest drug particles were entrapped on rougher surfaces while larger drug particles were dispersed in the air. The results showed that the processing of lactose carrier particles by roller compaction was immensely beneficial to improving DPI performance, primarily due to increased surface roughness at the macro-scale.