The Mechanism of Magnesium Stearate to Modify Aerosol Performance in Dry Powder Inhaled Formulations

Martin Jetzer^1,2, Bradley Morrical¹, Marcel Schneider¹ & Georgios Imanidis²

¹Novartis Pharma AG – Global Development, Novartis Campus, Lichtstrasse 35, Basel, 4056, Switzerland

²University of Basel, Department of Pharmaceutical Sciences, Klingelbergstrasse 50, Basel, 4056, Switzerland

Summary

The potential of the force control agent (FCA) magnesium stearate (MgSt) to enhance the aerosol performance of lactose-based dry powder inhaled (DPI) formulations was investigated in this study. Two different blending methods of lactose and MgSt (0.5% w/w) have been examined. The in vitro aerosol performance in terms of aerodynamic particle size distribution (APSD) and fine particle fraction (FPF) of the fluticasone propionate (FP) and salmeterol xinafoate (SX) DPI formulations were evaluated with the Next Generation Impactor (NGI) and also with single particle aerosol mass spectrometry (SPAMS). Furthermore, the electrostatic behaviour of the FP and SX formulations was investigated. The aim was to generate insights in electrostatic charge generation during powder manufacturing and capsule actuation in the inhalation device (i.e. unit dose capsule inhaler) and its effect on the aerosol performance.

The dispersion of MgSt in the binary mixture with lactose carrier strongly depends on the blending method, and the particle interactions between drug and carrier particles are substantially affected by the choice of blending technique. Measurements of the dynamic electrostatic charge show that there is a significant difference in electrostatic charge between the different formulations tested. This affects particle detachment from the carrier and thus impacts aerosol performance for FP. SX did not show significant electrostatic effects for any of the blends. Compared to blends with pure lactose, low-shear blending of MgSt increases the FPF of the adhesive model drug SX, while high shear blending significantly increases FPF of both SX and FP. This allows fine control of aerosol performance of a DPI by an adequate choice of the blending technique.