Summary

Mannitol is a suitable alternative to lactose in dry powder inhalation formulation. To tune the fine particle fraction, the addition of fines to saturate active sites, reduce press-on forces or form API-fines-agglomerates could be considered. Furthermore, the addition of a coating agent like magnesium stearate (MgSt), which makes the surface of the carrier particles hydrophobic and reduces the strength of agglomerates, could also be an option. The following study evaluates the effect of the addition of fines, the addition of MgSt and a combination of both to a mannitol carrier-based formulation. Two different model APIs were used, budesonide and salbutamol sulphate. Powder rheological measurements were performed to get a closer look into the flowability and a better understanding of the volumetric dosing process. The aerodynamic performance of the formulations was examined by using three different inhaler devices (one capsule-based inhaler and two reservoir-based inhalers). All three optimisation methods increased the inhalable fraction but to a different extent. The addition of fines increased the respirable fraction, but it was found that the sole mixing of MgSt achieved significantly higher FPFs. By reducing the interparticle forces, the API was able to get dispersed better from the carrier and formed agglomerates were easier to destroy. With a further addition of fines a shift in the deposition profile to a higher mass median aerodynamic diameter was recognized. Thus, the deposition profile can be tailored by the addition of fines.