Powder Flow: Powder characterization techniques for dry powder inhaler applications

At the very heart of dry powder inhaler technology lies a demanding powder engineering challenge. Particles in the sub-5 micron range - the ideal for deposition in the lung - tend to be cohesive, making them difficult to handle and disperse. Achieving efficient dispersion of the active to a respirable size is a primary goal of formulators. However, addressing manufacturing issues at an early stage is also beneficial. Accurate and precise manufacture is vital for consistent drug delivery, a critical step being the extraction of a very small, representative dose into a capsule or blister pack. Developing formulations that disperse efficiently during inhalation and which process well is a daunting task but certain tools can help. One such is the powder rheometer which combines bulk, shear and dynamic powder testing to give the fullest insight into the nature of a DPI formulation.

Fine particle dose (FPD) is the amount of active that, on the basis of size will tend to penetrate into the lung, and is a commonly applied in vitro measure of delivery efficiency. Developing a formulation that disperses easily and effectively is the key to achieving a high FPD since with most DPIs the energy available for aerosolization of the dose is simply that provided by the inhaling patient. As many DPI formulations use a carrier to improve flowability characteristics, this dispersion step is complex and involves stripping the active from the larger excipient particle.

The mechanisms of DPI dose dispersion are not yet fully understood but, because it proceeds via a process of fluidization, the response of the powder to air is pertinent. One of the unique features of dynamic powder characterization - measurement of the powder in flow - is that it enables the testing of powders in an aerated or fluidized state. With non-cohesive powders, air flowing upwards through the sample separates and lubricates the individual particles. Consequently flow energy, a dynamic parameter, decreases rapidly with increasing air flow rate. More cohesive materials on the other hand resist the flow of air, which ultimately tends to channel through the bed rather than uniformly fluidizing it.

Recent research has demonstrated a direct correlation between aerated flow energy and FPD for DPI formulations. Formulations that present a relatively high resistance to flow when aerated produce a higher FPD than those with lower aerated flow energy. Visualization studies suggest that this is because formulations with a greater resistance to flow ultimately fluidize via a single highly energetic event rather than dispersing less successfully through a more gradual process of erosion.

While aerated flow energy is a good powder descriptor for studying dispersion behavior, research has shown that for DPI manufacture, and more specifically dosing, flowability and compressibility more accurately reflect in-process performance. Consistent dosing relies on filling a known volume - a die or dosator, for example - with powder of constant bulk density. Poorly flowing powders result in incomplete filling while those that are relatively compressible inhibit compression of the powder plug to the defined bulk density.

This analysis highlights the need for multi-faceted powder measurement in the development of truly optimal DPI formulations. Product use and manufacture place very different demands on the formulation and meeting these builds robust performance into the product from the outset. Universal powder testers such as the FT4 powder rheometer deliver data that quantify diverse aspects of powder behavior in a reproducible, cost and time efficient manner. Such instruments are therefore a productive solution for this especially demanding application.

Introduction

Following Tim Freeman's articles on Powder Flow,

understanding powder behaviour to optimise process performance, increase productivity and improve quality.

Author Biography

Tim Freeman, Managing Director, Freeman Technology

Tim Freeman is Managing Director of powder characterisation company Freeman Technology for whom he has worked since the late 1990s. He was instrumental in the design and continuing development of the FT4 Powder Rheometer® and the Uniaxial Powder Tester. Through his work with various professional bodies, and involvement in industry initiatives, Tim is an established contributor to wider developments in powder processing.

Tim has a degree in Mechatronics from the University of Sussex in the UK. He is a mentor on a number of project groups for the Engineering Research Center for Structured Organic Particulate Systems in the US and a frequent contributor to industry conferences in the area of powder characterisation and processing. A past Chair of the American Association of Pharmaceutical Scientists (AAPS) Process Analytical Technology Focus Group Tim is a member of the Editorial Advisory Board of Pharmaceutical Technology and features on the Industry Expert Panel in European Pharmaceutical Review magazine.  Tim is also a committee member of the Particle Technology Special Interest Group at the Institute of Chemical Engineers, Vice-Chair of the D18.24 sub-committee on the Characterisation and Handling of Powders and Bulk Solids at ASTM and a member of the United States Pharmacopeial (USP) General Chapters Physical Analysis Expert Committee (GC-PA EC).

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