An insufficient understanding of (statistical) interactions between variables in the formulation and dispersion of adhesive mixtures for inhalation leads to a low utility of studies concerning these processes. Drug detachment from lactose carriers is described in a basic manner to improve the understanding of the interplay between variables. It is suggested that the effect of any variable on drug detachment depends on how it alters the so-called energy ratio distribution during
inhalation and on the initially detached drug fraction. Therefore, interactions between the effects of component and process variables on the detached drug fraction and any inhalation variable that alters the initially detached drug fraction (e.g. inhalation flow rate) are always to be expected. In addition, interactions between variables arise if one variable affects the way in which another variable alters the energy ratio distribution. This may occur if these variables have a
non-additive effect on drug detachment through the same so-called ‘principal factor(s)’ of the mixture, or if one variable affects the relevance to drug detachment of changes in the principal factors that are caused by another. It follows that multi-order interactions between variables are very likely to occur. Anticipating these interactions will increase the utility of future studies and the efficacy of quality by design approaches to the development of dry powder inhalation products.