Interparticle interaction in powder inhalates

Carrier particles are used in dry powder inhalers (DPIs) for the therapy of asthma bronchiale and COPD to improve the flowability of active pharmaceutical ingredient (API) particles used for pulmonary application. In order to reach the tiny airways of the deep lung the API has to exhibit an aerodynamic diameter of 1 m to 5 m. Particles of this size are rather cohesive and show poor flow properties and dosing. To overcome this problem the API is attached to the carrier in a mixing process and adheres by van der Waals forces. During inhalation it is essential that the API detaches again from the carrier, otherwise it would impact together with the carrier in the upper airways or throat. So, interparticle interactions play a key role in this kind of formulations. On the one hand they have to be high enough that uniform dosing is possible and on the other hand low enough that drug detachment from the carrier surface during inhalation is guaranteed. The aim of this work is tailoring interparticle interactions via surface modification of glass beads as carrier particles. Glass beads were used as model carrier because of the various options to modify their surface chemically as well as physically, without affecting other factors that also influence interparticle forces like particle shape and size. Via chemical and physical surface processing, glass beads with different surface roughness could be generated. Hydrofluoric acid treatment leads to golf ball like structure with large surface irregularities, mechanical treatment of glass beads by friction and impaction in a ball mill leads to roughnesses only visible at large magnifications of the SEM. By using grinding materials with different hardness and varying the processing time surfaces with different shades of roughness could be generated. By contrast chemical surface treatment with sodium hydroxide (NaOH) tends to smooth the glass beads surface. By chemical surface treatment with different silanes also the surface chemistry and polarity of the glass beads could be changed. Adhesion force measurements between spray dried salbutamol sulphate particles and the modified glass beads showed that interparticle interactions can be tailored by the use of different surface modifications. By implementation of these data in the simulations of the collaboration partner (Prof. Martin Sommerfeld, Mechanical Process Engineering, Martin-Luther-University, D-Halle) the prediction of drug detachment of the API from the carrier should be possible when the adhesion force is known.