Surface Modification of Micronized Drug Powders to Improve Aerosolization via Mechanical Dry Powder Coating

Objective: To improve the efficiency of aerosolisation in an air flow of two model micronized drug powders by dry mechanical modification of particle surfaces. Method: Two model drugs, micronized salbutamol sulphate (SS) and salmeterol xinaofoate (SX) powders were dry coated with magnesium stearate using a mechanofusion approach. The powder resuspension and de-agglomeration behaviours were evaluated from a simple inhaler device actuated with a standard airflow, using a real-time particle sizer (Spraytec) to assess the aerosols generated. The work was further supported by examining aerodynamic behaviour using an in vitro twin stage impinger. Results and Discussion: The Spraytec results indicated that a substantial improvement in de-agglomeration efficiency during the aerosolization could be achieved for micronized drug particles, with a decrease of D₅₀ from 8.1 µm to 5.0 µm for SS and from 7.7 µm to 4.5 µm for SX, after the mechanofusion processing. The fine particle fraction values from the in vitro assessment were also increased significantly from 51% to 69% for SS and from 59.9% to 73.1% for SX. Conclusions: This study is part of a programme to better understand the flow and aerosolisation changes afforded by dry coating of a range of materials, and indicated that the aerosolisation performance of carrier-free powder formulations can be substantially improved by reducing the intrinsic cohesion of the powder via appropriate particle surface modification.