Controlled Release

1
Controlled Release
Drug released In one shot
Conventional system
Disintegration

• Some consequences
• Antiobiotics-5 pills per day
• Anti-malarials-take pills everyday for upto 2
  months
• Contraceptive pills in humans-daily
• Diabectics-regular insulin injections

The alternative Slow release
Time 0 Time t
Time tfinal
The drug is released either by diffusion
or degradation
The final is exhausted
A device is produced containing the drug
2
Examples

• Nicotine patches for transdermal delivery
• Contraceptives for pets! Not in the UK though
• Slow release niacin
• Slow release insulin
• Etc etc.

3

• films with the drug in a polymer matrix
  -monolithic devices)
• the drug contained by the polymer -reservoir
  devices
• polymeric particles (microparticles, microspheres
  or nanoparticles) reservoir and matrix devices
• drug contained by a polymer containing a
  hydrophilic and/or leachable additive
• enteric coatings -ionise and dissolve at a
  suitable pH
• Polymers with attached 'pendant' drug molecules
• Release rate is controlled dynamically eg, the
  osmotic pump

4
Drug in a matrix
Drug mixed in with matrix
1) Polymer degrades
Degradation from surface first drug released as
polymer degrades
Polymer matrix is either 1) a
degrading polymer or 2)
a swollen polymer-a hydrogel
Drug diffuses out over time Hydrogel restricts
diffusion
5
Reservoirs

• Eg capsules

Drug dispersed or dissolved In another medium
Permeable or degrading membrane
Drug diffuses through the membrane
6
Polymer particles
Nano particles 30-300 nm
Microparticles 0.5-50 mm
Sub-micron particles 300nm-1000 nm
Not definitive size ranges but this is usually
what is meant by these terms
Various physical methods for incorporating drugs
eg pan coating, air-suspension coating, spray
drying etc.
7
Example of a chemical method
Interfacial polymerisation-the Nylon rope trick
Polymer film forms at the interface
Di Acid chloride
diamine
Drugs trapped in particle
8
Polymer drugs- in cancer
Water soluble polymer
Degradable linker
Drug
Targeting group
The drug is inactive while attached to the
polymer
Linker degrades and releases drug
Polymer binds to cell
9
Sterilization
A critical aspect in all healthcare Unknown until
the pioneering works in the 19th
century Materials dependent
Plastics/rubbers-degradation is an issue
Metals, ceramics No real issues-they will
intense heat treatment
Sterilization Destruction of pathogens-necessary
for any surgery Disinfection a lower grade
sterilization- spores are not killed
10
Typical disinfectants
Alcohols-methanol, ethanol etc. Surfactants
Generally disrupt bacterial membranes
eg
11
Surfactant molecules
Surfactants mix with membrane lipids
Membranes rupture
Cytoplasm leaks and bacterium dies
12
The method depends on the degradation properties
of the polymer
13
Dry heat -not good for plastics -poor thermal
conductivity-good for metals Autoclaving- uses
steam-lower temperatures than dry heat -good
penetration -used in hospitals for multi use
devices -but problems with sensitive
polymers eg polyesters Irradiation- very
common- both g or b- -high through puts
-issues with polymer degradation Gaseous
chemicals -ethylene oxide - OK most
plastics -chlorine dioxide-relatively new
14
Here is a general guide for a range of polymers
used in medical devices