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 mu m-200 mu m and active pharmaceutical ingredient (API) particles in the size range of 0.5 mu m-5 mu m 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 <40 mu m. The experiments are performed using the Novolizer (R) as DPI device. Electrostatic charge measurements are conducted using an open-end Faraday cup. The study revealed that the netcharge increases with an increasing amount of carrier fines and an increasing air flow rate. Further the netcharge decreases with increasing particle size and the presence of APL Finally investigations on the dependence of tribo-charging on the number of actuations of the device revealed that the netcharge arising on adhesive mixtures released in 50 consecutive doses from the DPI is almost the same for each dose at an air flow rate of 60 l/min whereas at 90 l/min there is a noticeable trend of decreasing netcharge over the number of actuations. (C) 2012 Elsevier B.V. All rights reserved.