Particle sizing is performed routinely in the pharmaceutical industry for quality assurance (QA), quality control (QC) and
helping to understand the behaviour of particulate systems. Particle shape has, however, received much less attention, even
though its importance has long been recognized by the industry. There are two main reasons for this.
The first involves the availability and accessibility of computing power. Microscopy was, and remains, the method of choice
for particle shape characterization.
Previously, images of particles had to be analysed manually — an exercise that is tedious, slow and prone to errors — and
the information obtained could not be fully utilized because there was neither a theoretical model nor enough computing power
to handle the data. The best practical solution was to reduce the information to some shape factor that captures one aspect
of the shape characteristics, but loses all the others. Such shape factors have frequently been used in conjunction with equivalent
spherical diameters for nonspherical particles. This tradition has prevailed to this day, even though computer power has increased
dramatically.
The second reason is that the industry has, over the years, accumulated a huge amount of historical data collected and stored
as equivalent spherical sizes and simple shape factors. Internal QC procedures and various national and international standards
are all based on such data. To change this tradition, three things need to happen. First, the technology of obtaining shape
information must be available, affordable, easy and fast enough for routine use. Second, the technology that can make full
use of shape information must exist and have demonstrable benefits that outweigh the effort and cost the industry incurs to
make the switch. The third and final push is probably from the actual or anticipated change of law or standards. Although
this is unlikely to happen before the first two become mature enough for practical applications, early adopters of new or
innovative technologies can be, and frequently are, rewarded with a competitive edge. In this article, methods for acquiring shape information are briefly reviewed and ways in which shape information may be used
to model structures at various length scales and to subsequently predict structure-related properties are described. These
generic numerical techniques have been used in sectors other than pharmaceutical. The purpose of this article is to introduce
them and illustrate their capabilities to the pharmaceutical industry.
Particle shape acquisition
A prevailing view regarding particle shape has been that the industry has enough trouble making the most of the size data,
which are much more readily available. Such an attitude is reflected in the market for particle size and shape analysers.
There are currently more than 400 size-analysis instruments, but only approximately 10% are designed to also perform shape
analysis. However, the past few years have seen a rapid increase in the number of commercial particle shape analysers, which
are being updated faster than ever before and many are now 21 CFR Part 11-compliant. This is a clear indication that more
attention is now being paid to particle shape by the industry as a whole.
Almost all instruments, marketed as particle shape analysers (e.g., Sysmex FIPA-3000 and PharmaVision 830 from Malvern; RapidVUE
from Beckman-Coulter; CIS-100 from Galai; and CamSizer from Horiba), are essentially automated optical microscopy systems
equipped with some powder dispersing mechanisms, and image acquisition and analysis capabilities. They offer a quick way to
characterize particle shapes for QA and QC purposes, but fall short on providing detailed three-dimensional (3D) shape information
that enables a quantitative link to be made between properties of individual particles and powder behaviour, because the instruments
only capture and analyse two-dimensional (2D) projections of particles. An up-to-date review of these 2D shape analysers can
be found in an authoritative book by T. Allen.1
There are several commercially available instruments that have been used to obtain 3D shape information of particles. One
such instrument is the X-ray micro tomography (XMT) scanner (e.g., SkyScan 1172). It operates on the same principle as medical
X-ray CT scanners, but with several important differences, including:
- the object, not the X-ray source/detector unit, is rotated
- a micro focus X-ray source with more power output capable of penetrating dense materials is employed
- nearly 1000 times higher spatial resolution (to approximately 1 µm/pixel) can be achieved
- costs only a fraction of a medical scanner.
