Investigating the Effect of the Force Control Agent Magnesium Stearate in Fluticasone Propionate Dry Powder Inhaled Formulations with Single Particle Aerosol Mass Spectrometry (SPAMS)

Martin Jetzer, Bradley Morrical, Marcel Schneider, Georgios Imanidis

A number of researchers are investigating the role of ternary force control agents (FCA’s) in pharmaceutical inhaled products with different analytical techniques. Various application processes such as mechanofusion and particle smoothing have been published to apply FCAs on carrier particles [1–3]. Nevertheless, a thorough mechanistic understanding of the role of FCA’s in dry powder inhalation (DPI) formulations is still largely missing.

In this study, the effect and impact on the formulation containing the FCA MgSt has been investigated in a FP, lactose based DPI formulation. Two different mixing methods of lactose and MgSt have been examined. The aerosol performance in terms of APSD and FPF of the DPI formulations was evaluated with cascade impaction studies with the NGI and analyzed with SPAMS.

High-shear blending of the lactose carrier together with the FCA magnesium stearate (MgSt) lead to a shift of the aerodynamic particle size profile (APSD)  of the active drug fluticasone propionate (FP) and the total number of particles to a higher number of smaller particles. The blending method applied to pre-blend the excipients strongly impacts the APSD and fine particle fraction (FPF) of FP. Both SPAMS and Next Generation Impactor (NGI) confirmed an increase of FPF for FP when adding MgSt to the formulation by high-shear mixing. Low-shear mixing of the excipient-blend did not increase the pharmaceutical performance of FP. The analytical techniques NGI and SPAMS successfully demonstrated that it is possible to distinguish changes in the formulation of DPI powders blended with different amounts of MgSt.

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