Influence of fine lactose and magnesium stearate on low dose dry powder inhaler formulations.

The behaviour of dry powder blends for inhalation, depending on the amount of fine lactose particles smaller than 10microm and the presence of magnesium stearate (MgSt), was studied in this work. A laser light diffraction method was developed to determine accurately size and volume fraction of these fine lactose particles in coarse carrier lactose (x(50) approximately 220microm). A linear relationship between measured volume fraction undersize at 10microm Q(3)(10microm) and added fine lactose could be established. Aerodynamic particle size distribution analysis of lactose showed that the fine lactose was attached to the coarse particles. In the presence of MgSt this interaction was increased. Consequently, the number of free active sites on the carrier surface was reduced and the investigated drug (formoterol fumarate dihydrate) was more effectively delivered. Addition of fine lactose and MgSt improved the aerodynamic performance the drug, as determined by resulting fine particle fraction, by 3% (for each 1% of added fine lactose) and 10%, respectively. Stability tests indicated that added MgSt was the most relevant of the studied parameter to achieve a stable aerodynamic performance. Its ability to protect the moisture uptake into the system was considered as rational for this effect.