Handle with care
UK universities seek new technique for handling nanoparticles in drug processing
PHARMACEUTICAL companies
may be able to use a more
environmentally friendly drug
processing method if researchers in
the West Midlands can successfully
develop a new technique for
handling nanoparticles.
Teams at Birmingham and
Warwick universities are hoping to
solve the problem of capturing and
preserving the properties of
nanoparticles produced during
supercritical fluid (SCF) precipitation
processes by combining it with
fluidised bed technology.
‘If you produce a drug substance
in the nanoparticle form, it is
impossible to get such a material to
flow; it agglomerates very easily and
is very difficult to handle and deal
with. We have got what we think is
a novel way of turning that into a
form that can be handled, using fluidised
bed technology,’ said
Warwick’s Prof Jonathan Seville.
Fluidised beds are widely used
in many industries as reactors, dryers,
agglomerators and coaters.
They are used in the pharmaceutical
industry for coating liquids on to
tablets and capsules, rather than
for handling powdered active drug
substances collected from SCF
processes. Fluidisation in the
process occurs when a fluid, usually
a gas, flows upwards through a
bed of solid particles and causes
them to be suspended, which
makes them easier to handle.
The SCF process involves
dissolving a drug in a supercritical
fluid, a fluid above its thermodynamic
critical point that possesses
properties of gas and liquid. By
adjusting the pressure, nanoparticles
from the drug can be
precipitated from the SCF.
‘We would normally use supercritical
carbon dioxide, which
means high pressures, typically
hundred of bars, but not necessarily
high temperatures,’ said Seville.
‘The supercritical fluid process on
the whole operates not much
above ambient temperature, unlike
a lot of conventional processes.’
Supercritical CO 2 is a good
solvent for certain kinds of drug
substances. While it may be possible
to dissolve some substances
directly in the supercritical CO 2,
insoluble drug substances would
have to be dissolved in another solvent,
such as ethanol, and the
supercritical CO 2 then used as an
antisolvent, resulting in a crystallisation
process.
According to Seville, SCF
processes have a number of
advantages over conventional crystallisation
processes.
‘When you precipitate out the
drug, it is a shock process, so
where most crystallisation
processes are quite slow, this is a
very fast precipitation — it happens
in fractions of a millisecond. The
result is you get very small and uniform
particles,’ he said.
Moreover, Seville said it is
sometimes possible to get a
different polymorphic form (substances
with the same chemical
composition but different crystal
structures) of the drug, which could
result in some drugs having more
active properties.
‘This sort of process has advantages
in producing potentially a
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Better for the environment: the new technique could capture and preserve the properties of nanoparticles for drug coating
the EnGIneeR 21 APRIL–4 MAY 2008 11
better product, but it also has very
strong environmental advantages
because most drug processing
involves large quantities of organic
solvents, most of which are environmentally
damaging and can
sometimes have toxicity problems
of their own,’ he added.
It is not unusual to have 100kg
of waste material for every kilogram
of active ingredient produced. With
the SCF technique, however, the
waste-cleaning element is avoided
because it is only CO 2 being used,
which can be recompressed or
recycled.
Conventional crystallisation can
be laborious in comparison,
because it involves dissolving the
drug in a solvent at temperature,
then cooling it to produce crystals.
The result is a varied distribution of
crystal size and sometimes imperfect
crystals, which can break up in
subsequent processing. They also
require washing to remove the solvent,
which is a process that may
be repeated several times to get the
desired product.
‘The washing stage is quite a
difficult one, whereas we have no
problem with that because if you
reduce the pressure, the CO 2 will
simply turn into a gas and come
off,’ said Seville.
While it is possible to achieve
the nanoparticulate drug substances
in the conventional
method, Seville said it was more
problematic because the bigger
particles have to be milled in air jet
mills, which fires them at each other
at very high velocity.
The main problems include the
particles not being uniform in size,
and the high-speed impact can
change the form of the drug and
make it less effective in the body.
As well as defining a technique
for handling the nanoparticles from
SCF particle production, the project
will cover the characterisation of
the products from the fluidised
beds and their conversion into
tablets or other forms of dosage.
It will not just be the pharmaceutical
industry that would benefit
from the project’s achievements,
however, as the researchers
said the new technology would
also help manufacturers of food,
toners, coatings, chemicals and
catalysts.
Anh Nguyen
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