Packing and flow performance of binary adhesive mixtures for inhalation of different drug loads and their relationships to aerosolisation

TL;DR

This study examines how the mechanical properties of adhesive mixtures affect their performance in drug delivery, finding that certain properties correlate with how well the drug disperses.

Contribution

The study identifies two groups of mechanical test methods and their distinct correlations with drug dispersibility, revealing insights into adhesive blend performance.

Findings

Packing density and shearing properties showed fluctuating relationships with drug load.

Shearing properties correlated with dispersibility, while permeability did not.

Blend architecture and adhesion layer structure influence both mechanical and dispersion properties.

Abstract

The aim of this study was twofold. First, to examine the mechanical properties (packing and flow) of a series of adhesive mixtures, consisting of two different lactose carriers and varying concentrations of budesonide, using a range of test methods. Second, to investigate if any of the test methods correlate with the dispersibility of the mixtures, i.e. the fine particle fraction and mass median aerodynamic diameter. The mechanical properties assessed included packing, shearing, permeability and compressibility. Dispersion data were generated using an impactor operated at two pressure drops (0.5 and 4 kPa). To explore correlations between the mixture properties, Principal Component Analysis and Pearson correlation were used as statistical tools.

The different test methods yielded different property-drug load relationships, which can be classified into two groups: First, packing density and shearing properties, and second, permeability and compressibility. The methods in the first group produced markedly fluctuating property-drug load relationships, characterised by two distinct waves. This type of property-drug load relationship was similar to that observed in the dispersion experiments, and significant correlations were found between shearing properties and dispersibility. Thus, any correlations between mechanical and dispersion properties depend on the choice of the test method used. The underlying cause of this co-variation is the parallel effect of both the blend architecture and the structure of the adhesion layer on mechanical and dispersion properties.

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•Packing and flow methods could be classified into two groups.•Correlation between mechanical properties and dispersibility depended on methods.•Dispersibility and shear properties had a similar dependency of blend architecture.•Permeability correlated to pore diameter but not to dispersibility.•Blend state is critical for several performance aspects of adhesive blends.

Packing and flow methods could be classified into two groups.

Correlation between mechanical properties and dispersibility depended on methods.

Dispersibility and shear properties had a similar dependency of blend architecture.

Permeability correlated to pore diameter but not to dispersibility.

Blend state is critical for several performance aspects of adhesive blends.

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