Adhesion forces in interactive mixtures for dry powder inhalers--evaluation of a new measuring method.

Dry powder inhalers mostly contain carrier based formulations where micronized drug particles are adhered to coarse carrier particles. The performance of the dry powder inhaler depends on the inhaler device, the inhalation manoeuvre and the formulation. The most important factor influencing the behaviour of the formulation is the adhesion force acting between the active ingredient and the carrier particles, which can be measured using different methods, for example the centrifuge technique or atomic force microscopy. In this study the tensile strength method, usually applied to determine cohesion forces between powder particles of one material, is optimized for adhesion force measurements between powder particles of unlike materials. Adhesion force measurements between the carrier materials lactose or mannitol and the drug substance salbutamol sulphate using the tensile strength method and the atomic force microscopy show higher values with increasing relative humidity. Consequently, the fine particle fraction determined using the Next Generation Impactor decreases with increasing relative humidity as a result of the enhanced interparticle interactions.