Performance tuning of particle engineered mannitol in dry powder inhalation formulations.

Abstract

Typically, smooth lactose particles are used as carrier in dry powder formulations for inhalation. Two classical approaches to improve their aerodynamic behaviour are the addition of fines (milled lactose) or magnesium stearate (MgSt). Mannitol (Parteck® M DPI) as an alternative carrier was used in this study. It has an irregular particle size distribution and a large and rough surface. This could be challenging for the detachment of micronised drug upon inhalation and it is unclear whether classic strategies for the optimisation of aerodynamic performance can be applied. In contrast, its rough surface could be an advantage in terms of drug load. To address these questions, the mannitol carrier was blended with two different drugs using various concentrations up to 50%. Self-produced mannitol fines and MgSt in different amounts and in combination were added. Blends were investigated regarding their in vitro aerodynamic performance, dosing behaviour and powder rheology. An addition of up to 30% drug load was possible while retaining good flowability and constant dosing behaviour. Despite the rough and indented carrier surface of the mannitol carrier, the addition of fines or MgSt increased the inhalable fraction, but higher concentrations of fines, as used for lactose blends, were necessary.