The permeability of a powder bed reflects its particle size distribution, shape, packing, porosity, cohesivity, and tensile strength in a manner relevant to powder fluidization. The relationship between the permeability and the performance of carrier-based dry powder inhalation (DPI) mixtures has, however, aroused controversy. The current study sought to gain new insights into the relationship and to explore its potential applications. We studied eight lactose materials as DPI carriers. The carriers covered a broad permeability range of 0.42–13.53 D and moreover differed in particle size distribution, particle shape, crystal form, and/or porosity. We evaluated the performance of inhalation mixtures of each of these carriers and fluticasone propionate after aerosolization from an Aerolizer®, a model turbulent-shear inhaler, at a flow rate of 60 L/min. Starting from the high permeability side, the inhalation mixture performance increased as the carrier permeability decreased until optimum performance was reached at permeability of ~ 3.2 D. Increased resistance to air flow strengthens aerodynamic dispersion forces. The inhalation mixture performance then decreased as the carrier permeability further decreased. Very high resistance to air flow restricts powder dispersion. The permeability accounted for effects of carrier size, shape, and macroporosity on the performance. We confirmed the relationship by analysis of two literature permeability–performance datasets, representing measurements that differ from ours in terms of carrier grades, drug, technique used to determine permeability, turbulent-shear inhaler, and/or aerosolization flow rate. Permeability provides useful information that can aid development of DPI mixtures for turbulent-shear inhalers. A practical guidance is provided.

CONCLUSIONS

Permeability is a useful measurement that can be used to predict the performance of carrier-based dry powder inhalation mixtures aerosolized by turbulent-shear inhalers. The current study tested eight lactose materials as dry powder inhalation carriers. Starting from the high perme- ability (low resistance to air flow) side, the inhalation mixture performance increases as the carrier permeability decreases until optimum performance is reached. Below the maximum-performance permeability, the inhalation mixture performance decreases as the carrier permeability further decreases. The relationship between the permeability of a carrier and the performance of the carrier-based inhalation mixture was prominent although it was challenged by using carriers different in terms of particle size distribution, content of fines, particle shape, crystal form, and/or porosity. It accounted well for effects of carrier size, shape, and macroporosity on the performance. The findings were further confirmed by analysis of two permeability–performance literature datasets. A practical guidance for formulation development was provided. The types and the magnitudes of adhesion forces in inhalation mixtures and dispersion forces generated in inhalers during aerosolization may quantitatively affect the relationship suggested by the current study. Investigation of the relationship parameters for different inhalers and for different coarse excipient (carrier)–fine excipient–drug combinations is the subject of future studies.

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