Figure SM1. ( ) Span, and ( ) Standard Error (SE) of Aspect Ratio/Flatness Ratio (AR/FR)

Figure SM1. (●) Span, and (▲) standard error (SE) of aspect ratio/flatness ratio (AR/FR) VS aspect ratio/flatness ratio (AR/FR) (mean±SE) for different fine mannitol particles. More elongated fine mannitol particles were less uniformly shaped and generated less size-homogeneous powders.

Figure SM2. Scanning electron microscope (SEM) images for different fine mannitol particles: spray dried mannitol (SDM) (a), commercial mannitol (CM) (b), cooling crystallized mannitol (CCM) (c), acetone crystallized mannitol (ACM) (d), and ethanol crystallized mannitol (ECM)(e).

Figure SM3. Aspect ratio determined by image analysis light optical microscopy in relation to aspect ratio determined by scanning electron microscopy (SEM) for different mannitol products.

Figure SM4. DSC traces of different fine mannitol products: spray dried mannitol (SDM), commercial mannitol (CM), cooling crystallized mannitol (CCM), acetone crystallized mannitol (ACM), and ethanol crystallized mannitol (ECM).

Figure SM5. Bulk density and tap density (mean±SD, n=4) obtained from lactose-salbutamol sulphate formulation (no fines) and lactose-salbutamol sulphate formulations containing different fine mannitol particles: spray dried mannitol (SDM), commercial mannitol (CM), cooling crystallized mannitol (CCM), acetone crystallized mannitol (ACM), and ethanol crystallized mannitol (ECM).

Figure SM6. Carr’s index (CI) and Hausner ratio (HR) (mean±SD, n=4) obtained from lactose-salbutamol sulphate formulation (no fines) and lactose-salbutamol sulphate formulations containing different fine mannitol particles: spray dried mannitol (SDM), commercial mannitol (CM), cooling crystallized mannitol (CCM), acetone crystallized mannitol (ACM), and ethanol crystallized mannitol (ECM).

Figure SM7. Comparison of SS-SS agglomeration between lactose-SS and lactose-SS-ACM formulations.

Figure SM8. % Coefficient of variation (CV) of salbutamol sulphate (SS) content obtained from lactose-SS formulation (no fines) and lactose-SS formulations containing 4.7% w/w of different fine mannitol particles:spray dried mannitol (SDM), commercial mannitol (CM), cooling crystallized mannitol (CCM), acetone crystallized mannitol (ACM), and ethanol crystallized mannitol (ECM);and % CV in relation to aspect ratio/flatness ratio (AR/FR)(mean±SE) of different fine mannitol particles. Fine mannitol particles with more elongated shape produced more homogeneous DPI formulation.

Figure SM9. Recovered dose (RD) and emitted dose (ED) (mean±SD, n≥3) obtained from lactose-salbutamol sulphate formulation (no fines) and lactose-salbutamol sulphate formulations containing different fine mannitol particles: spray dried mannitol (SDM), commercial mannitol (CM), cooling crystallized mannitol (CCM), acetone crystallized mannitol (ACM), and ethanol crystallized mannitol (ECM).

Figure SM10. Recovery and emission of salbutamol sulphate obtained from lactose-salbutamol sulphate formulation (no fines) and lactose-salbutamol sulphate formulations containing different fine mannitol particles: spray dried mannitol (SDM), commercial mannitol (CM), cooling crystallized mannitol (CCM), acetone crystallized mannitol (ACM), and ethanol crystallized mannitol (ECM).

Figure SM11. Mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of salbutamol sulphate obtained from lactose-salbutamol sulphate formulation (no fines) and lactose-salbutamol sulphate formulations containing different fine mannitol particles: spray dried mannitol (SDM), commercial mannitol (CM), cooling crystallized mannitol (CCM), acetone crystallized mannitol (ACM), and ethanol crystallized mannitol (ECM).

Figure SM12. Amounts of SS deposited on (●) MSLI stage 1, (♦) stage 2, (▲) stage 3, (■) stage 4, and (○) filter in relation to aspect ratio/flatness ratio (AR/FR,mean±SE) of different fine mannitol particles.