Triboelectric characteristics of mannitol based formulations for the application in dry powder inhalers

Abstract

Abstract Inhalation powders may be charged by triboelectrification upon aerosolization and release of the powder from the inhaler device due to frequent contacts and high impact velocities between the particles and the inhaler material. This is particularly challenging in dry powder inhaler (DPI) technology where usually adhesive mixtures of carrier particles in the size range of 50 μm–200 μm and active pharmaceutical ingredient (API) particles in the size range of 0.5 μm–5 μm are used. In these adhesive mixtures it is crucial that the API particles adhere to the coarser carrier particles to ensure good flowability and dosing behavior. However during aerosolization the API particles should detach from the carriers in order to reach the deeper lung. This means that the performance of such adhesive mixtures used in DPI devices is strongly affected by inter-particle forces which are further affected by electrostatic charge. Sign and magnitude of the arising charge is on the one hand influenced by the contacting material, relative humidity and impact velocity and on the other hand by particle characteristics like particle size, particle shape and surface roughness. For these reasons the aim of this work is to investigate which factors actually influence the charging process during powder aerosolization and release from the inhaler and how it can be controlled. In the present study the influence and interactions of four practice-relevant factors is checked using statistical design of experiments. These are the carrier particle size, the aerosolization air flow rate, the API content in the adhesive mixtures and the addition of carrier fines