The Importance of Interactions Between Carrier and Drug Particles for the Application in Dry Powder Inhalers

The design of formulations intended for inhalation is a major challenge since many different factors need consideration in order to guarantee major drug delivery. This becomes especially important in dry powder inhalation. Balanced inter-particle interactions between carrier and drug particles are key factors for an optimal aerodynamic performance. This work combines an experimental approach utilising spherical glass beads as model carrier and simulations of device properties as well as particle-particle interactions to gain deeper understanding of processes during inhalation and their effect on aerodynamic performance. Surface roughness modification of the carrier proved to influence the effective drug loading of distinct drug particles. Moreover, surface topography had a major impact on the aerodynamic performance as micron-sized indentations drastically reduced the fine particle fraction (FPF). This could be linked to their ability of sheltering drug particles from the airstream during inhalation. Nano-scale roughness on the other hand led to a significant increase of the FPF. The impact of the inhalation device itself was also taken into account. The conducted numerical calculations (CFD) have provided more insight into carrier particle transport and drug detachment in the case of carrier-based formulations. A multi-scale approach was adopted to numerically analyse the performance of inhaler devices. First, the motion of carrier particles through a swirl-type inhaler was simulated to provide information on flow stresses acting on carrier and on wall collision statistics. Fully resolved simulations of carrier covered by hundreds of drug particles in connection with measured adhesion properties showed that flow-induced drug detachment will only be possible if the van der Waals force between carrier and drug is very weak (i.e. requiring surface modification). However, in the considered swirl-type inhaler the wall collision number of carriers is quite high, being the reason for an efficient drug detachment through inertia. A developed wall collision detachment model revealed that almost 100% of the drug powder is detached within the inhaler, which does not correspond to experimental observations. Consequently, also drug powder deposition on the inhaler walls needs to be accounted for, in order to allow correct predictions of the emitted dose.