Title:Recent advances in the fundamental understanding of adhesive mixtures for inhalation
Volume: 21
Issue: 40
Author(s): Floris Grasmeijer, Niels Grasmeijer, Paul Hagedoorn, Henderik Willem Frijlink and Anne Haaije de Boer
Affiliation:
Keywords:
Carrier particle size distribution, carrier surface roughness, cohesion-adhesion balance, drug content, fines, interactive mixtures,
ordered mixtures, powder dispersion.
Abstract: Adhesive mixtures for inhalation are the most widely used type of formulation in dry powder inhalation
products. Although they have been the subject of active research, the relationships between properties of the starting
materials, the mixing and dispersion processes, and the dispersion performance of this type of formulation are
generally poorly understood. Interactions between relevant variables have been mentioned as an important cause.
By reviewing the effects on mixture dispersion performance of the most widely studied formulation variables we
try to find out whether or not the understanding of adhesive mixtures has improved in recent years. We furthermore
propose an approach that may potentially accelerate the process of understanding. General conclusions concerning
the effects of the variables considered cannot be drawn, because inconsistent findings are reported throughout the
literature for all of them. These inconsistencies are indeed largely the result of interactions between variables of the
formulation and dispersion processes. Mechanisms for most of the observed effects and interactions have been proposed, but they often
remain unproven and, therefore, speculative. We have attempted to condense the knowledge from the literature into a theoretical framework
that is intended to help explain the interplay between variables. According to this framework, only few mixture properties are key
to understanding the effects of and interactions between formulation variables. Therefore, we suggest that the development or optimisation
of techniques to accurately characterise these mixture properties could be an effective approach to further the fundamental understanding
of adhesive mixtures for inhalation and enable their rational engineering.
