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A presentation comparing polymers and ceramics used in controlled release technologies. The characteristics of polymers and the synthesis of bioceramics are presented, together with drug load micro foam and freeze granulation technologies. The current research and developments made by Ceram in this field are also presented.Courtesy of Dr Xiang Zhang, Ceram.
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by Ceram
New Concept Controlled-Release Technology
Water Glass and Bioceramic
as
Drug Delivery Vehicles
BIO-Europe Spring 2011, Milan
14-16 March 2011
Dr Xiang C Zhang
This work by Ceram is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License
by Ceram
Controlled Release Technology
Comparison
of
Polymer and Ceramic
by Ceram
• The pharm market: ~$200 billions/year
• New drug development: very difficult, slow and costly
• Available drugs: plenty of drugs on the market but the ways to deliver
drugs are not safe or effective in most circumstances
• Controlled Release Technology (CRT): offers a new way to deliver drugs to
make them safer and more effective: for example
• Maintain a therapeutic level for
prolonged periods of time
• Varying release rates in control
• Long life drug and/or targeting
drug Controlled release
not in control
Time
Toxicity level
Too low level
The
rap
eu
tic
Tra
ge
t
Why Controlled Drug Delivery?
by Ceram
CRT and Polymer
Polymers are mostly investigated and employed as drug carriers/delivery
vehicles; common technology:
• Encapsulation: surrounding drug molecules with a solid polymer shell
Polymer Drug
• Entrapment involves the suspension of drug molecules within a polymer
matrix
Polymer Drug
• Drug release mechanisms: diffusion, erosion (surface, bulk or both of them)
by Ceram
Characteristics of Polymer
For example: Polyglycolide or Polyglycolic acid (PGA) biodegradable for the
controlled release of small and medium-sized biologically active
compounds
Chemistry
Mass Loss
Time
SAXS: Long period size variation
Molecular and microstructure unstable
Crystalline phase
Crystalline phase
Physics
amorphous
phase
by Ceram
Characteristics of Polymer
Other features:
• Polymer degradation starts from amorphous phase, both crystalline and
amorphous phase changes, etc
• Not a well-known fact: polymer degrades from the centre of the ‘bulk’
polymer, also accompanying changes in pH values
Bulk PGA SAXS Results: Long Range Period
amorphous
amorphous
amorphous
Crystalline phase
amorphous
Crystalline phase
Crystalline phase
Crystalline phase
Crystalline phase
by Ceram
Case I: Bioceramics
by Ceram
Design Microstructure:
• Type of ceramic: HA, substituted X-HA, Silica, alumina, etc
• Size and size distribution of ceramic powders
• Type of binders: organic, inorganic and hybrids
• Particle size and porosity control: Ceram has over 20 years’ experience
using:
• Freeze Granulation Technology: This technology allows us to produce a
range of particle sizes and pore sizes from nano to micro, even mm scale
Drug Loaded Micro Foam - DLMF
by Ceram
Freeze Granulation Technology
Controlled particle size and porosity for loading
drugs
by Ceram
Drug Loaded Micro Foam - DLMF
Controlled release from a
model ceramic DLMF
good stability good control g
oo
d p
ote
ntia
l fo
r
dru
gs
an
d o
the
r a
ctiv
e in
gre
die
nts
by Ceram
Case II: Sol-Gel Water-Glass
by Ceram
Sol-Gel Water-Glass
Drug embedded in solid water glass matrix
Water-Glass Drug
Drug embedded within a porous matrix
Water-Glass
Drug
Pores
by Ceram
Sol-Gel Water-Glass
0
0.4
0 0.5 1 1.5 2 2.5 3 3.5
Dru
g in
so
lutio
n (
mg
/ml)
Time (hour)
SA1
SC1
Acid catalysed reaction
by Ceram
Case III: Normal Water-Glass
by Ceram
Extensive Glass Experience
Freeze dry granulates made by
atomising a ‘fine glass powder in
water suspension’ and then
quenching in liquid nitrogen.
After sublimation, a porous glass
granulate is made. This is then
gently sintered, to encourage the
fine powder particles to ‘neck’.
The result? A stronger granulate
capable of absorbing drugs and
other active ingredients as a
vehicle for controlled release
technology.
by Ceram
Not Pure Research; a Manufacturer Too
Product
In-house Atomiser
• Molten feed flow (chamber pressure)
• Nozzle diameter
• Argon gas flow through disc at nozzle
by Ceram
Current Research
Bioceramic & Healthcare Materials and Forming Technology
• multi-element-substituted hydroxyapatite (HA)
• skincare
• emulsion: zeta potential for drug, bone ceramic, shampoo studies…
• nano ceramic powder
Implantable Devices
• degradation in bioactive resorbable composites: Poly(alpha-hydroxy
acids) and calcium phosphate
• bioactive PEEK
• hip & knee: toughened ceramics
• bioactive low shrinkage cement
• new ceramic polymer hybrid
Controlled Release Technology
• controlled release bioglass (cosmetic)
• soluble glass for drug release
• bioceramic for controlled release technology