Transcript Prof. David Woolfson Medical Device Issues School of Pharmacy

Medical Device Issues
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Pharmacy
Prof. David Woolfson
Devices
Medical Device
A device implanted permanently or temporarily in
the body for a mechanical/structural purpose.
Usually manufactured by extrusion or injectionmoulding (polymeric devices)
Drug Delivery Device
A device intended to deliver a drug for prophylactic
or therapeutic purposes. Usually, such devices
control the rate at which the drug is made available
to the body (controlled release devices
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Hybrid device
A medical device with a primary
mechanical/structural function and a secondary
drug delivery function, either for device protection or
targeted drug delivery.
Devicerelated
problems
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
Insertion pain & tissue trauma

Haemocompatibility

Device encrustation - morbidity

Device-related Infection - mortality

>250,000 device-related infections/year in the
UK cost >£100million due to longer
hospitalisation and more aggressive treatment

There is now substantial interest in bioactive
medical devices that encompass a drug
delivery function
Foley
urinary
catheter
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Catheter
issues
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
Urinary catheterisation is frequently employed in
clinical and domiciliary care of patients.
Catheterisation may be short or long-term
(indwelling, Foley-type) or intermittent (Nelatontype)

Catheter blockage due to encrustation with
complex inorganic salts, resulting in device
failure due to obstruction of flow, remains a major
problem in longer-term use, as does devicerelated infection

Tissue trauma due to insertion, and also upon
removal, is a further problem with most types of
catheterisation

Surface formation of microbial biofilm, leading to
UTI
Endotracheal
tube
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ET TUBES from ICU PATIENTS at (clockwise)
4h, 8h, 12h
Biofilm
formation
Surface of
endotracheal tube
retrieved from
an ICU patient
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4h
24h
48h
5d
Ureteral
stents
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from GORMAN SP et al BRITISH JOURNAL OF UROLOGY
73 (6): 687-691 1994
Cardiovascular
stents
angioplasty balloon
mounted stent
stent in situ
Drug-Eluting Stents (stainless steel, nitinol)
The drug-eluting stent is basically a bare metal
stent that is then coated with a slow-to-moderaterelease drug formulation, sometimes embedded
in a polymer. It is hoped that this will prevent or at
least reduce restenosis, reclosure of the coronary
artery, one of the biggest limitations of
angioplasty and causes for repeat procedures
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Medical
Devices economics
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
The rapid evolution of clinical medicine exerts a
continuing demand on manufacturers

Manufacturers with a high cost base must add
value to their lower-end products by making
significant technological advances in order to
compete with commodity suppliers, e.g. in
continence care, respiratory, cardiovascular
sectors

Real clinical improvements are needed to
demonstrate cost-savings to healthcare systems
and justify higher reimbursement costs for
healthcare systems

Manufacturing and design improvements (e.g
smooth device surface) not sufficient - bioactive
devices ultimately required
Medical
Devices polymers
poly(vinyl chloride)
plasticised or unplasticised
poly(styrene)
crystalline or amorphous (tacticity)
[ CH2
CH2
]n
poly(ethylene)
HDPE or LDPE
poly(urethane)
HDPE or LDPE
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silicone repeat unit
crosslinked to form an elastomer
Device
coatings
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
Device coatings can add lubricity,
biocompatibility, and antimicrobial action to
device surfaces. Coatings can be used to
release drugs or make implanted devices more
visible to imaging systems

Many device coatings are hydrophilic polymerbased formulations, usually hydrogels

Enhanced device lubricity is one major reason
for coating, e.g catheters and guidewires can be
spray coated with a thin layer of
polytetrafluoroethylene (PTFE)
Bioactive
coatings
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
Coatings may be applied to non-polymeric
devices fabricated from stainless steel, platinum
or nitinol (nickel titanium)

Drug delivery coatings that render a device
‘bioactive’ are now of major interest. Typically, a
drug in a carrier hydrogel coating is released as
the hydrogel imbibes water from surrounding
biological fluids and swells

Coating technologies presently include dipcoating, spray-coating, co-extrusion and chemical
grafting to polymers, whereby the drug is added
to the coating mix pre-process

Relevant active agents include non-antibiotic
antimicrobials, antibiotics and inorganic metallic
elements such as silver
Controlled
release
mechanisms

diffusion controlled
• reservoirs (membranes)
• matrices (monoliths)
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• bioerosion/degradation

chemically controlled

solvent activated

externally ‘smart’ controlled • e.g. sensor-based
• pendant chain
• osmotic pressure
• swelling
Diffusion
controlled
systems
Matrix (monolithic)



drug uniformly
distributed
through polymer
matrix
no danger of drug
dumping
first-order kinetics
Q
Q
√t
t
Reservoir




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drug core surrounded by nonbiodegradable polymer
properties of drug and polymer govern
diffusion rate
‘drug-dumping’ if membrane ruptures
zero-order kinetics from ‘constant
activity’ source
Q
t
Effect of bioactive agents released from silicone
Bioactive
biomaterials
Miconazole nitrate Nalidixic acid Gentamicin sulphate Ampicillin
30
25
20
Zone of Inhibition
(mm)
15
10
5
Ampicillin
0
Gentamicin sulphate
1
2
3
Nalidixic acid
4
5
6
Miconazole nitrate
7
Time (days) of Repeated Microbial Challenge
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8
NewLEIF
opportunities
in bioactive
biomaterials
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
Alteration of surface topologies (nanoengineering)

Direct implantation on devices surfaces
(polymeric, metallic) of inorganic elements
with antimicrobial properties, e.g silver ,
without the need for coating

Surface implantation on preformed devices
of organic compounds (MW < 500) with
antimicrobial activity through generation of
highly charged species

Laboratory and clinical assessments of
efficacy