[Pharmwaste] New green methods for coating drugs in plastics

[Tenace, Laurie]

I've always said that we can expect drug delivery systems to change, making
some of the problems with pharmaceuticals in the environment decrease. Here
is a new drug delivery system that looks like it is one small step in that
direction. Better drug delivery means better metabolism, smaller quantities
of drug used because of better metabolism, and probably better tolerance by
the patient which could also result in fewer unfinished prescriptions and
less disposal - in this case, drug manufacturing would also use fewer toxic
solvents. 

http://www.news-medical.net/?id=29883


New green methods for coating drugs in plastics 
Medical Research News 
Published: Friday, 14-Sep-2007    

Green chemistry is being employed to develop revolutionary drug delivery
methods that are more effective and less toxic - and could benefit millions
of patients. 
Chemists at The University of Nottingham are developing new methods for
coating drugs in plastics, using methods that do not damage the latest
generation of delicate 'biopharmaceutical' drugs which are at the cutting
edge of modern medical treatment. 

Conventional methods of coating drugs can use high temperatures and harsh
solvents - damaging the active components of biopharmaceuticals before they
have even reached the patient. But using green chemistry techniques pioneered
at Nottingham, the bioactive elements of the drug remain completely
effective, so the patient receives the maximum benefit of the therapy. The
plastic is designed to release the drug over a controlled period of time;
minimising the number of injections a patient will need, and maximising the
effect of the drug. 

The principles of green chemistry herald a radical new approach that is
'benign by design' - both in terms of the process itself, its impact on
patients and on the environment. Green chemistry promises to make the
chemical industry cleaner and safer, while producing better, purer products
in the process. 

In a presentation at the British Association for the Advancement of Science
Conference in York on September 12, Professor Steve Howdle outlined the green
chemistry processes being pioneered at The University of Nottingham,
particularly the use of supercritical fluids to replace conventional solvents
such as benzene and chloroform. 

Professor Howdle's research focuses on exploiting the unique properties of
supercritical carbon dioxide (CO2). A supercritical fluid is a solvent, with
physical properties between those of a gas and a liquid. At near-room
temperature and under modest pressure, supercritical carbon dioxide blurs the
boundaries between liquid and gaseous states. 

The process can be used to make polymer drug coatings, using biodegradable
plastics, just like those used in dissolvable surgical stitches. The polymer
is used to encapsulate the drug before it is injected into the body. 

Conventional chemical processes often use high temperatures or volatile, and
potentially toxic, solvents such as chloroform, benzene, and other volatile
organic compounds (VOCs). Solvent residues may remain in the product after
manufacture and these can be toxic to the patient and to the environment -
requiring special handling and recycling measures to prevent them from
escaping into the atmosphere. 

They can also cause degradation of the drug. Many bioactive drug compounds
are adversely affected by high temperatures and conventional solvents, which
can destroy up to 50 per cent of the drug molecules intended to help the
patient. 

But the clean green chemistry techniques being developed at Nottingham aim to
remove these conventional solvents from the process altogether. Because
supercritical fluids can be used to support solvent-free chemical processes,
creating new techniques that would be difficult or impossible to achieve in
normal solvents or by conventional processing. 

Professor Howdle's research has demonstrated that biodegradable polymers can
be plasticised at near room temperatures using supercritical CO2. 

The low temperature means delicate bioactive components, such as growth
factors or proteins, can be mixed into the plasticised polymer without any
loss of activity. 

The process overcomes a major obstacle to the development of new drug
delivery devices because it means that patients will be able to receive
biopharmaceuticals which do not survive conventional chemical processing
because they are either solvent or sensitive to heat. 

Professor Howdle said: "Many very potent new drugs based on proteins are
being discovered all the time. But a major problem the pharmaceutical
industry faces is that they have to be wrapped up in plastic to be delivered
to the patient, so that there is controlled release of the drug over time. 

"Many of these new proteins are fragile and are damaged by high temperatures
and harsh solvents used in conventional processes. Our process works in CO2
at close to room temperatures so the molecule is not damaged by the mixing
process, and we don't use normal solvents we don't have toxic residues left
behind in the product and potentially ending up in the patient. 

"The plastics are solids but when they are put under high pressure from CO2,
they turn into liquids - they melt, and under these conditions, the bioactive
drugs can be mixed in. So we take particles of the drug and wrap every single
one up in biodegradable polymer, for injection under the skin." 

Once injected, the polymer begins to degrade and the drug starts to be
released and is picked up by the bloodstream - but this is a gradual process,
occurring over the course of several days or a week. This provides a
controlled release of the drug prolonging the length of time over which
active therapeutic is released at the delivery site. 

The polymer used is a biodegradable plastic based on lactic acid, which is a
natural compound produced in the body that the body is able to get rid of in
the usual way. It is used in dissolvable stitches and has been used in the
pharmaceutical industry in various guises for 30 years. 

Compared to conventional methods for giving drugs to patients, controlled
drug delivery via injection has many advantages including reduced dosing
frequency and toxicity, improved efficiency and convenience and therefore
increased patient compliance. 

Professor Howdle added: "Biodegradable polymers are particularly attractive
for use in drug delivery, as once introduced into the body they require no
retrieval or further manipulation and are degraded into soluble, non-toxic
by-products. Different polymers degrade at different rates within the body
and therefore polymer selection can be tailored to achieve desired release
rates. 

"Thus the process allows for gradual, controlled release of a drug, reducing
side effects and improving quality of life. For the patient, it could mean
the end of twice-daily injections - in favour of an injection once a week." 

Drug encapsulation techniques using green chemistry techniques are currently
in advanced tests at spin-out company Critical Pharmaceuticals Ltd. - set up
in 2002 by Prof Howdle and colleagues - and expected to proceed to clinical
trials soon. Since the drugs and polymers being used have already been
approved separately, the process is likely to be available for patients
sooner than might otherwise be expected with an entirely untested process. 

As well as new methods of drug delivery, the use of supercritical fluids
offers cleaner, residue-free processes that can be harnessed to produce other
new polymer materials ranging from enhanced bullet proof plastics through to
detergents and coatings and even porous scaffolds for tissue engineering.
 
 

Laurie J. Tenace
Environmental Specialist
Florida Department of Environmental Protection
2600 Blair Stone Road, MS 4555
Tallahassee, Florida 32399-2400
PH: (850) 245-8759
FAX: (850) 245-8811
Laurie.Tenace at dep.state.fl.us 

Mercury web pages:
http://www.dep.state.fl.us/waste/categories/mercury/default.htm

Unwanted Medications web pages:
http://www.dep.state.fl.us/waste/categories/medications/default.htm




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