Continued Investigation Into the Influence of Loaded Dose on the Performance of Dry Powder Inhalers: Surface Smoothing Effects

ABSTRACT

The aerosolization of salbutamol sulfate, measured as fine particle dose (FPD_LD) and fine particle fraction (FPF_LD) (<6.4 μm mass median aerodynamic diameter), from two sieved (63–90 μm) lactose monohydrate carriers, one as supplied, one smoothed by controlled surface dissolution, was studied. In general, no significant variation in FPD_LD was observed at drug loadings between 10 and 63.5 μg and 10 and 135 μg for the surface dissolved and as supplied lactose monohydrates, respectively. Increasing the drug load above these levels resulted in linear increases in FPD_LD with increasing drug load with the surface dissolved lactose monohydrate exhibiting higher FPD_LD and FPF_LD. This suggests that, at lower drug loadings, areas of the carrier exhibiting higher adhesion, so-called active sites, were being preferentially occupied and filled. Since there was no evidence of drug agglomeration using scanning electron microscopy, the observations suggest that the number and range of such higher energy “active sites” can be reduced by modifying the surface roughness, that is, energies, of the carrier.

KEYWORDS:

• Active sites
• Dry powder inhaler
• Lactose
• Smoothing