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

Abstract

The adhesion force between micronized drug particles (Salmeterol Xinafoate) and lactose monohydrate carrier particles in interactive powder mixtures has been determined. Artificial particle size distributions of the carrier powder were produced from fine (< 20 μm), medium ( 20 μm to < 70 μm), and coarse ( 70 μm) carrier particle fractions. Using three different grades of lactose monohydrate, in total 60 different particle size distributions were prepared. These blends differed in their mean particle size and amount of fine particle fraction, 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 the carrier material and that an increased amount of fines caused a large increase in the adhesion force. Preconditioning of the carrier powder by blending it alone by a set procedure was found to lead to autoadhesion contact between the fine and coarse carrier particles, which resulted in an alteration of the surface structure of the coarse carrier particles due to corrasion. However, the degree of change in surface structure depended on the initial surface roughness of the carrier particles. Corrasion as a means of improving the adhesion properties of interactive powder mixtures with respect to their function as dry powder inhalations was found to be useful only if the coarse carrier particles had a surface roughness above an apparent rugosity threshold level of 1.2-1.3 μm.