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

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Controlled Release Technology

Comparison of Polymer and Ceramic

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Why Controlled Drug Delivery?

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

not in control Toxicity level Therapeutic Traget

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Controlled release Too low level

Time

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 Physics
Crystalline phase amorphous phase

Crystalline phase
SAXS: Long period size variation Molecular and microstructure unstable

Mass Loss

Time
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Characteristics of Polymer
Bulk PGA SAXS Results: Long Range Period Crystalline phase amorphous Crystalline phase amorphous Crystalline phase amorphous
Crystalline phase amorphous Crystalline phase

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
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Case I: Bioceramics

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Drug Loaded Micro Foam - DLMF

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

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Freeze Granulation Technology

Controlled particle size and porosity for loading drugs

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Drug Loaded Micro Foam - DLMF

good stability good control

Controlled release from a model ceramic DLMF

drugs and other active ingredients

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good potential for

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 Pores

Water-Glass
Drug

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Sol-Gel Water-Glass
0.4

Acid catalysed reaction

Drug in solution (mg/ml)

SA1
SC1

0 0 0.5 1 1.5 2 2.5 3 3.5

Time (hour)
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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

In-house Atomiser

Molten feed flow (chamber pressure)

Nozzle diameter Argon gas flow through disc at nozzle

Product

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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
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