The interaction between carrier rugosity and carrier payload, and its effect on drug particle redispersion from adhesive mixtures during inhalation

Abstract

The effectiveness of press-on forces (defined as the adhesive forces between drug and carrier particles) in relation to carrier payload as the result of collisions between carrier particles during the mixing process of an adhesive mixture, has been investigated. Three different carriers of the same size fraction (250–355 μm), but with completely different surface rugosity were studied. It could be shown that this effectiveness depends on the carrier rugosity. The fraction of drug detached from the carrier particles during inhalation appeared to decrease faster with increasing carrier payload for crystalline carriers than for granular carriers. Apparently, increasing the volume of the carrier surface cavities increases the drug mass that can find shelter from the press-on forces during mixing. By measuring the size distribution in the aerosol, it could also be shown that the press-on forces may increase the size of the particles that are detached. This seems to be the result of drug particle re-agglomeration on the carrier surface during mixing. On the other hand, when press-on forces are highly ineffective, an increase in the size of detached particles may also be the result of incomplete break-up of natural drug agglomerates. Finally, it could be shown that when the press-on forces are highly effective, the effect of mixing time is small.