Recent advances in the fundamental understanding of adhesive mixtures for inhalation

Author(s):

Floris Grasmeijer, Niels Grasmeijer, Paul Hagedoorn, Henderik Willem Frijlink and Anne Haaije de BoerPages 5900-5914 (15)

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.

Keywords:

Carrier particle size distribution, carrier surface roughness, cohesion-adhesion balance, drug content, fines, interactive mixtures, ordered mixtures, powder dispersion.

Affiliation:

University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

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