Influence of storage conditions on ternary dry powder inhaler formulations

M Hertel¹, E Schwarz², M Kobler², S Hauptstein², H Steckel³ & R Scherließ¹

¹Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany

²Meggle Excipients and Technology, Megglestr. 6 – 12, 83512 Wasserburg am Inn, Germany

³Deva Holding AS, Istanbul, Turkey

The aim of this study was to investigate the influence of storage conditions on ternary powder mixtures of commercially available lactose grades. Due to the high fines content, these formulations should be particularly prone to changes upon storage. For this purpose the influence of high relative humidity (rH) on the fine lactose particles was investigated. Significant differences in the surface texture, particle size, water content and other properties, such as the amorphous content and the anomer ratio, could be shown. Furthermore, solid bridges between the particles formed by recrystallization processes were visible on SEM images. Subsequently, ternary powder mixtures were prepared with the hydrophobic model drug budesonide and three different storage conditions were tested. At 0 % rH, there was no change in the aerodynamic behaviour, whereas the FPF increased at 45 % rH. This can be explained by the dissipation of electrostatic charge which had been caused by the mixing process. Storage at 75 % rH proved to be disadvantageous, as the capillary forces gained through the absorbed water increased and solid bridges could form.