Adhesion forces in interactive powder mixtures of a micronized drug and carrier particles of various particle size distributions

The adhesion force between micronized drug particles (Salmeterol Xinafoate) and lactose monohydrate carrier particles in interactive powder mixtures h as been determined. Artificial particle size distributions of the carrier p owder were produced from fine (<20 mu m), medium (greater than or equal to 20 mu m to < 70 mu m), and coarse (greater than or equal to 70 mu m) carrie r particle fractions. Using three different grades of lactose monohydrate, in total 60 different particle size distributions were prepared. These blen ds differed in their mean particle size and amount of fine particle fractio n, and were either mono- or bi-modal. It was found that the adhesion force between drug and carrier particles depended on the mean particle size of th e carrier material and that an increased amount of fines caused a large inc rease in the adhesion force. Preconditioning of the carrier powder by blend ing it alone by a set procedure was found to lead to autoadhesion contact b etween the fine and coarse carrier particles, which resulted in an alterati on of the surface structure of the coarse carrier particles due to corrasio n. However, the degree of change in surface structure depended on the initi al surface roughness of the carrier particles. Corrasion as a means of impr oving the adhesion properties of interactive powder mixtures with respect t o their function as dry powder inhalations was found to be useful only if t he coarse carrier particles had a surface roughness above an apparent rugos ity threshold level of 1.2-1.3 mu m.