An investigation into the effect of fine lactose particles on the fluidization behaviour and aerosolization performance of carrier-based dry powder inhaler formulations.

The effect of milled and micronized lactose fines on the fluidization and in vitro aerosolization properties of dry powder inhaler (DPI) formulations was investigated, and the suitability of static and dynamic methods for characterizing general powder flow properties of these blends was assessed. Lactose carrier pre-blends were prepared by adding different lactose fines (Lactohale® (LH) 300, 230 and 210) with coarse carrier lactose (Lactohale100) at 2.5, 5, 10 and 20 wt% concentrations. Powder flow properties of lactose pre-blends were characterized using the Freeman Technology FT4 and Schulze RST-XS ring shear tester. A strong correlation was found between the basic flow energy (BFENorm) measured using the Freeman FT4 Rheometer and the flowability number (ffc) measured on Schulze RST-XS. These data indicate that both static and dynamic methods are suitable for characterizing general powder flow properties of lactose carriers. Increasing concentration of fines corresponded with an increase in the normalized fluidization energy (FENorm). The inclusion of fine particles of lactose resulted in a significant (p < 0.05) increase in fine particle delivery of budesonide and correlated with FENorm. This trend was strongest for lactose containing up to 10 wt% LH300. A similar trend was found for the milled lactose grades LH230 and LH210. However, the increase in FENorm upon addition of milled fines only corresponded to a very slight improvement in the performance. These data suggest that whilst the fluidization energy correlated with fine particle delivery, this relationship is specific to lactose grades of similar particle size.