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

xiang.zhang@ceram.com

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?

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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)

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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

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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

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Case I: Bioceramics

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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

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Freeze Granulation Technology

Controlled particle size and porosity for loading

drugs

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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

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Case II: Sol-Gel Water-Glass

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Sol-Gel Water-Glass

Drug embedded in solid water glass matrix

Water-Glass Drug

Drug embedded within a porous matrix

Water-Glass

Drug

Pores

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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

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Case III: Normal Water-Glass

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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.

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Not Pure Research; a Manufacturer Too

Product

In-house Atomiser

• Molten feed flow (chamber pressure)

• Nozzle diameter

• Argon gas flow through disc at nozzle

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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