The role of fine excipient particles in adhesive mixtures for inhalation

Abstract

Despite the fact that adding fines improve the drug dispersion performance during inhalation, the scarcity of mechanistic insight into the formulation process, independent of the aerosolization, has kept the dispute on the underlying improvement mechanism open. We therefore simulate ternary formulations (carrier, drug, fines) in a vibrational cell to explore the mixing mechanism and the effect of particle size and loading ratio of fines on formulation performance. Results suggest that the buffer theory is a critical contributory mechanism since it curtails the carrier's collision rate and, therefore, decreases agglomerate breakage. Consequently, relatively larger drug aggregates are formed over the carrier, which eventually experiences greater detachment forces. A simple dispersion test is performed to evaluate drug detachment rate at wall-collision. An excess of cohesive fines, or using larger fines, diminishes the rotational kinetic energy of coarse particles by lumping them together. This reduces drug agglomerate breakage and leads to poor mixing.