NEWS
Pharma find
Purity and quality of chemical compounds can be monitored and controlled with process analytical technology
THE MANUFACTURE of pharmaceuticals
could be made cheaper
with a new system that monitors
the crystallisation of chemical compounds
used for drugs.
The process analytical technology
(PAT) tool includes a probe,
which collects images of the crystallisation
process inside a
pharmaceutical reactor, and software
to determine the size and
shape of the drug compound crystals.
The information gathered can
give indications on the purity and
quality of the product.
‘The feeling is that if we go to a
culture of full process understanding
we will get cheaper products,’
said Prof Kevin Roberts of Leeds
University’s Institutes of Process
Research and Development and
Particle Science and Engineering.
His research team worked with
industrial scientists at Perdix
Technologies in the Netherlands to
develop and commercialise the
probe, which they combined with
Morphologi, commercially available
image analysis software developed
by the UK’s Malvern Instruments.
Roberts said until now there has
been little effort made to monitor
and control the crystal formation in
pharmaceutical manufacturing.
He said Leeds has developed a
technique that uses powder X-ray
diffraction to analyse crystal forms
of a drug while it is being processed
(The Engineer, 16 June).
‘In general we don’t actually
control the formation of crystals in
the manufacturing process and that
means that product properties of
crystals can be quite variable,’ he
said.
‘So after crystallising the active
pharmaceutical ingredient of a drug
compound you might get a range of
sizes and shapes of crystals.’
Roberts said this means before
the product can be formulated into
a tablet, the particles must be
processed so they attain the same
size and physical properties.
‘Now we want to make the
crystals in such a way they formulate
directly,’ he said.
10
Shapely: software may help determine the size and shape of crystal compounds and could lead to cheaper products
The new In-Situ Particle Viewer
(ISPV) probe would film inside the
reactor so operators can see
exactly what is happening to the
crystals as they are forming. If a
crystal were forming in an irregular
manner, the operator would be able
to adjust the conditions inside the
reactor to correct it.
One parameter they could
change, Roberts said, would be the
rate at which the crystal is cooled.
Roberts said that when the
probe is combined with the
image analysis software it is capable
of revealing information that
pharmaceutical manufacturers
never had before.
Roberts said the part that
makes analysis of crystals so challenging
is that it is difficult to attain
measurements of products that are
not spherical.
‘The image analysis software
automates the process and it can
tell you lots of things about
the crystal, such as the shape
distribution and the distribution
of perimeters of particles,’ he said.
‘If the crystal was breaking up
under the fluid mechanics’ shear
stress inside the vessel you
could see it from the shape
distribution.’
This kind of monitoring and control,
he said, will help the
pharmaceutical manufacturing
process become faster and more
efficient, which will cut waste, save
money and shorten the time it takes
drugs to get to market.
Roberts said increased control
over pharmaceutical manufacturing
processes would be a ‘paradigm
shift almost identical to the semiconductor
industry’.
He said: ‘Essentially we’re
working towards developing highquality
Six Sigma manufacturing
processes for the pharmaceutical
sector, very much mirroring the
approaches already adopted by
high-tech sectors such as microelectronics.’
Leeds worked with a number of
global pharmaceutical companies
on the project, including GSK,
Pfizer and AstraZeneca. The ability
to monitor the crystallisation
process will make an obvious difference
in their industry, Roberts
said, since nearly 80 per cent of
all drug compounds are made
that way.
However, the technique could
also have lesser known applications
outside the pharmaceutical
industry.
‘Crystallisation is also used in
making chocolate, sugar, salt, all
agrichemicals and speciality materials
and dyes pigments,’ he said.
‘It’s a very common technique.’
Roberts added that the global
agribusiness Syngenta and the
UK-based nuclear technology specialists
Nexia Solutions were
involved in the project and are interested
in using the system for their
manufacturing processes.
‘Crystallisation is very important
for manufacturing of nuclear fuel as
well,’ he said.
Siobhan Wagner
the EnGIneeR 29 SEPTEMBER–12 OCTOBER 2008
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