Powder Flow: Powder characterization techniques for capsule filling

Capsules are widely used to provide metered doses for oral and pulmonary drug delivery. For oral administration fill weights are typically in the range 50 to 500 mg but for dry powder inhalers, dose size is far smaller, principally within the range 0.5 to 15 mg. These smaller volumes, in combination with the fine particle size of inhaler formulations, are particularly challenging. Capsule filling success relies on characterizing powders in a way that allows for a correlation between measured properties and the powder’s behavior in the dosing equipment. Research has shown that bulk, shear, and dynamic powder properties all influence capsule filling performance, so powder testers with all three methodologies are uniquely applicable.

Commercially applied capsule filling technologies include: dosing plate and tamping pin; dosator and pin; and vacuum drum. The mechanics of equipment operation are different in each case but in terms of process steps there are many similarities. In basic terms, capsule filling involves the extraction of powder from a bulk supply into a confined space of known volume, compaction of the dose to ensure a complete fill at consistent bulk density, and transfer of the compacted plug to an appropriate receptacle.

Dynamic measurements directly quantify the ease with which a powder flows. Basic flow energy (BFE) characterizes flow under compacting motion while specific energy (SE) reflects how easily the powder flows when unconfined. Studies have shown that both parameters are relevant to capsule filling processes, during which powders initially flow under low stress into an empty space or die, but are then subject to compaction, as more powder is squeezed into the die in order to achieve the desired fill. Direct correlation has been observed between BFE and SE, and dose weight consistency, a key indicator of process performance.

During compaction, the compressibility of the powder is important. Compressibility is a bulk parameter that defines how the volume of a powder sample changes with applied pressure. With a highly compressible powder a compacting force tends to act locally, consolidating the powder most densely in the region directly beneath the point of application of the force; dose density is inconsistent. Less compressible powders, in contrast, give more homogeneous compression as the applied axial force is more efficiently transmitted through the dose. Such powders are therefore easier to compact to consistent bulk density during the filling process, supporting the attainment of uniform dose weight.

Finally, shear testing offers insight into the strength of the powder plug, and of likely interactions between the powder and processing equipment surfaces. Conventional shear test data quantify the cohesivity of the sample, while wall friction data, which are derived using a similar technique, allow the comparative investigation of the likelihood of powder adhesion to the processing surface. An ideal formulation exhibits sufficient cohesivity to form a stable powder plug for transfer, but has sufficiently low interaction with the processing equipment to avoid contamination of the equipment surface.

This last point illustrates the importance of balancing powder properties to achieve optimal process performance. For capsule filling, powder testers that deliver shear, bulk and dynamic properties provide the comprehensive data set needed to formulate and design towards this balance and can therefore be a cost-  and time-efficient choice.

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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