The influence of particle size distribution and surface roughness of carrier particles on the in vitro properties of dry powder inhalations

The influence of the amount of fine carrier particles, the shape of the par ticle size distributions, and the surface roughness of the coarse carrier p articles on the aerodynamic properties of interactive powder mixtures from Salmeterol Xinafoate and lactose monohydrate have been investigated. In a f urther set of experiments, the influence of preconditioning the carrier pow der by blending was compared with the performance of an unconditioned powde r. A higher amount of fine carrier particles in interactive mixtures was found to improve the aerodynamic properties of dry powder inhalations. Fine carr ier particles may form agglomerates with the micronized drug and deposit in the air stream according to the aerodynamic properties of the agglomerates , rather than that of the single particles. However, this effect also appea rs to be linked to the surface roughness of the more coarse carrier particl es. A smoother surface of the coarse carrier particles may lead to formatio n of autoadhesion layers around them, which can cause embedment of the micr onized drug particles and thus hinder detachment during inhalation. The results obtained using preconditioned lactose monohydrate powders as op posed to unconditioned lactose monohydrate powders suggest that preconditio ning by blending can be disadvantageous or of no importance in terms of the aerodynamic behavior of dry powder inhalations for some lactose monohydrat e batches, while it improves these properties for others. The surface rough ness of the coarse carrier particles influences the effect that preconditio ning has on the performance of dry powder inhalations. The data suggest tha t carrier materials with relatively smooth surfaces are indifferent to prec onditioning in terms of the aerodynamic properties of the dry powder inhala tions, whereas carrier powders with comparatively rough surfaces lose their ability to function as carrier particles for a micronized drug in a dry po wder inhalation. The results indicate that a rugosity of the carrier partic les of about 1.3 mu m is optimal in terms of the function of a dry powder i nhalation if preconditioning is sought.