The inclusion of a small amount of fine particle excipient in a carrier-based dry powder inhalation system is a well researched technique to improve formulation performance and is employed in the pharmaceutical industry. The removal of intrinsic fines from a lactose carrier has been found to decrease formulation performance, whereas adding fines of many different materials into formulations increased performance. Changing the particle size of these fines, the amount added and the technique by which they were prepared also affected formulation behaviour. Despite this body of research, there is disagreement as to the mechanism by which fines improved formulation performance, with two main hypotheses presented in the literature. The first hypothesis suggested that fines prevent the drug from adhering to the strongest binding sites on the carrier, whilst the second proposed that fine particles of drug and excipient form mixed agglomerates that are more easily dispersed and deaggregated during aerosolisation. The evidence in support of each hypothesis is limited and it is clear that future research should aim to produce stronger mechanistic evidence. The investigation of interparticulate interactions using techniques such as atomic force microscopy and inverse gas chromatography may prove useful in achieving this aim.

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The in situ generation of excipient fines affect bulk powder properties of DPI formulations, which directly affects fluidization and aerosolization behaviour of DPI formulations. The study suggests an alternative mode of action by which fines increase DPI formulation performance.