(752c) The Influence of Crystals, Particles and Powders On the Performance of Dry Powder Inhalers

Dry powder inhalers (DPIs) are an attractive means of delivering drugs to the lung. The fluidization, entrainment and de-aggregation of a DPI formulation is a complex relationship between the patient’s inspiratory effort, the air flow field generated within a device and the cohesive properties of the powder bed.

The inter-relationship between factors including particle size, particle shape, distribution of interparticulate and mechanical forces govern the performance and efficacy of DPI drug delivery systems. However, quantitative measurements of these properties and their under-lying relationships remain difficult to discern.

This presentation will focus on some key developments in understanding the relationships between the governing properties of DPIs and how these properties can be harnessed to develop designer formulation systems for DPIs.

INTRODUCTION

The ability to modify the flowability, deaggregation and dispersion of particles in a well-defined particle size range is a key requirement for the delivery of therapies to the lungs using dry powder inhalers (DPIs). The de-aggregation and dispersion of particles from DPIs is controlled by interfacial forces, and therefore governs the performance and efficacy of medicaments delivered to the lung by DPIs.

Several physicochemical factors can directly influence these properties, amongst which the mesoscopic surface structure of particulates plays a dominant role. However, quantitative measurements of these effects are difficult to discern, particularly as the size of particles approaches the micrometer dimensions. However, quantitative colloid-probe atomic force microscopy (AFM) measurements of the spatial distribution of the interactive forces, over and upon contact with the substrate surface have allowed changes in solid-state properties to be directly related to particle adhesion. Furthermore, this approach has enabled the ability to relate particle adhesion to the performance of DPI drug delivery systems.

Another critical component of delivery of dry powders to the lungs is related to the powder fluidisation process within the delivery device. The process of fluidization is related to many factors such as particle size, particle shape, bulk density and powder flowability. The influence of each of the components on the fluidization process is complex, however the development of a fluidisation energy measurement has provided a significant insight into specific relationship between powder flow, cohesive properties of the powder and DPI performance.

The presentation will specifically focus on the current limitations in the processing of sub-10mm particulates for DPIs, highlighting the direct influence of particle shape, surface morphology and interfacial properties on particle interactions. In addition, key developments in particle engineering techniques in modifying the particle architecture and surface geometry will be explored. The presentation will also focus on how rheometric properties of granular materials may be a critical tool in the development of powder-based formulations for inhaled drug delivery.