Creating tomorrow’s solutions

Colloidal anhydrous siliCa i Pharma

hdK®

Pharmaceutical Factbook

welCome to the waCKer Family oF PharmaCeutiCal ProduCts

HDK® is a registered trademark of Wacker Chemie AG.

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WACKER has been producing and refining its brand of HDK® colloidal anhydrous silica for over 40 years. Our integrated closed-loop technol-ogy, statistical process control and highly efficient reactor dynamics produce exceptionally pure grades of inorganic, colloidal anhydrous silica. These grades are especially well suited for pharmaceutical appli-cations.

Fascinatingly Versatile Although HDK® colloidal anhydrous silica is an established and highly successful product, WACKER continues to push forward with its R&D to seek new poten-tial solutions for further boosting product performance and quality. The extensive selection of both hydrophobic and hydrophilic HDK® grades and HDK® dispersions offers highly versatile and comprehensive solutions for a wide range of pharmaceutical applications.

Focused on Quality With our long experience in the control and vertical integration of the colloidal anhydrous silica manufacturing process, we are able to provide ultra-high purity products which are consistent from batch to batch, allowing our customers to enjoy uniform production performance.

With competence centers in the major regions of the world, we are here to support your requirements.

The HDK® production sites are certified worldwide in accordance with the ISO 9001 and ISO 14001 standards, which are a constituent part of WACKER’s Group certification.

Unparalleled SupportBy spending about 5–6 % of sales on R&D, we are determined to support you with innovative research laboratories, scientific knowledge and advanced ana-lytics. This dedication makes WACKER one of the most research-intensive chemical companies worldwide.

the BasiC Colloidal anhydrous siliCa reaCtion ProCess – Purity oF the highest Class

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Isolated primary particles do not exist as individual units outside the flame

Particle diameter 5 – 50 nm 100 – 500 nm >> 1 μm

1,200 – 1,500 °CSiCl4 + 2H2 + O2 SiO2 + 4HCl

SiO 2

SiO 2

SiO 2

SiO 2Air

HDK® colloidal anhydrous silica – formation in a flame

Reactor Molecules Protoparticles Primary particles Aggregates Agglomerates

WACKER has been producing colloidal anhydrous silica for the world market for more than 40 years, and has con-tinually optimized its production pro-cesses ever since. HDK® is produced at multiple sites by an integrated, efficient and environmentally compat-ible process that saves energy and raw materials.

Hydrophilic HDK® with a Large Surface Area The production parameters are res- ponsible for the excellent properties of hydrophilic, pure and odorless HDK®.

Colloidal anhydrous silica is formed by hydrolysis at over 1,000 °C. This is achieved by introducing chlorosilanes into an oxyhydrogen flame, producing SiO2 primary particles about 5–50 nanometers (10–9 m) in size. In the flame, the primary particles fuse together permanently to form large units, or aggregates (100–1,000 nm in size). That is to say, individual primary particles only exist in the reaction zone itself.

On cooling, the aggregates mechanically entangle to form agglomerates, known as tertiary structures. The aggregates have sizes in the range of microns. HDK® has a very high specific surface area (BET) because of the small diameters of its primary building blocks. The primary particles that are fused together in the aggregates finally arrange themselves into agglomerates. This inherently large surface area-to-mass ratio causes intense interparticulate interactions, which are the result of attractive disper-sion and dipolar forces. And that is precisely the reason for the outstanding properties of HDK®.

hdK® Colloidal anhydrous siliCaProduCt range

ConsistenCy and Purity

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Standard Grades

Specific surface area (BET) [m2/g] Hydrophilic HDK® Hydrophobic HDK®

~ 50 HDK® D05

~ 100 HDK® C10

~ 130 HDK® S13 HDK® H13L

~ 150 HDK® V15 HDK® H15, HDK® H17

~ 200 HDK® N20 HDK® H18, HDK® H20

HDK® N20 Pharma HDK® H2000

~ 300 HDK® T30 HDK® H30

~ 400 HDK® T40

HDK® dispersions and further special grades are available upon request

WACKER only authorizes HDK® Pharma grades for use in pharmaceutical applications. The use of other grades is not supported by WACKER.

Typical analytical data of HDK®

Trace element impurities

Element Measured levels(mg/kg)

Element Measured levels(mg/kg)

Ag < 2 K < 2

Al < 2 Mg < 2

As < 2 Mn < 2

Ba < 2 Mo < 2

Bi < 2 Na < 2

Ca < 2 Ni < 2

Cd < 2 Pb < 2

Co < 2 Sn < 2

Cr < 2 Sr < 2

Cu < 2 Ti < 2

Fe < 2 Zn < 2

Ge < 2 Zr < 2

Hg < 1

Total < 20

Inorganic impurities

Element Measured levels(mg/kg)

Cl < 100

Standard tests: • BET surface area • Sieve residue • pH in a 4 % aqueous dispersion

Typical general properties: Tap density: approx. 40 grams/liter Loss on drying (2 hours at 105 ºC): < 1.5 % SiO2 content: > 99.8 %

Analytical methods for elements: • Flame AES and ICP • “<” indicates the detection limit has been reached

The figures are only intended as a guide and should not be used in preparing specifications.

hdK® – exCellent as an exCiPient For oPtimum Quality

Whether your primary goal is gaining a competitive edge, maximizing your product’s capabilities or optimizing your production processes, HDK® colloidal anhydrous silica is the right choice. We understand your needs precisely and develop integrated solutions to fit your particular market or product application.

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A typical tablet contains:

Active ingredient

Filler/diluent

Lubricant, glidant & anti-adherent

Flavorings & colorings

Binder

Disintegrant

BinderHDK® helps hold a tablet together

LubricantHDK® helps improve release properties

SorbentHDK® helps as a moisture scavenger and adsorbs some liquid active ingredients

Filler/diluentHDK® helps manage tablet dosage

DisintegrantHDK® helps control disintegration

GlidantHDK® helps free-flow

hdK® – CertiFied Quality

Pharmaceutical RegulationsColloidal anhydrous silica is approved as an excipient in pharmaceutical appli- cations. HDK® N20 Pharma complies with pharmaceutical monographs and the specifications given in the corresponding monographs “silica, colloidal anhydrous” of the European Pharmacopeia and “colloidal silicon dioxide” of the US Pharmacopeia. HDK® N20 Pharma meets the purity requirements for “light anhy-drous silicic acid” in the monograph of the Japanese Pharmacopeia 16th edition (March 2011), as well as the purity requirements for “colloidal anhydrous silica” in the monograph of the British Pharmacopeia 2008, Volume II.

HDK® N20 Pharma is in compliance with regulation Title 21, Code of Federal Regulations part 314.420 as interpreted in “ Guidelines for Drug Master Files” (HEW FDAO 79-3072).

HDK® N20 Pharma is fully registered a US Type IV Drug Master File.

Additional Information

European UnionColloidal anhydrous silica may be used as a direct food additive in accordance with Regulations (EU) No. 1129 and 1130/2011 (superseding Directive 95/2/EC).It is also approved as an additive in plastic food contact materials in compli-ance with Regulation (EU) No. 10/2011 (superseding Directive 2002/72/EC).

HACCPHDK® N20 Pharma is certified for HACCP.

KosherHDK® N20 Pharma is Kosher certified for use in Kosher milk and meat products.

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PerFormanCe attriButes

Solids and Powders – Tablets, Capsules, Powders • Improves product free-flow properties by reducing aerated density • Improves compaction properties of tablets and capsules by coating larger raw materials • Facilitates compression by reducing particle interaction • Acts as a spacer between particles, distributed as a mono-particulate layer on the powder surface (reduces surface roughness) • Improves solubility of certain APIs • Adsorbs moisture from hygroscopic materials • Adsorbs liquids. Can convert liquids into powders depending upon loading level • Reduces incompatibility between different components of a preparation by encapsulating powdery substances • Improved disintegration in dissolving tablets • Prevents formation of powder bridges

Gels, Suppositories and Transdermals • Modifies and controls viscosity • Stabilizes suspensions • Stabilizes suppositories • Improves gel clarity • Improves and controls thickening • Improves uniformity of raw material distribution in formulated products

Liquids, Creams, Suspensions • Modifies and controls viscosity • Stabilizes gels and creams • Stabilizes suspensions and emulsions • Improves and controls thickening • Prevents hard settling, sedimentation and striation in formulated products • Enhances suspension and stops hard packing / settling in aerosols

Production Process and End Product • Incorporates cutting-edge expertise and production technologies • Synthetic origin - not of animal origin thus infection with

bovine spongiform encephalopathy(BSE) not expected to be present

- not of plant origin thuscontamination with geneticallymodified organisms (GMO) not expected to be present

• Substances such as herbicides, organic solvents, animal products, fungicides, insecticides, aflotoxins, dioxins, and furans are not added intentionally • Does not form a culture medium for microbes

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PaCKaging

Pallets with Paper BagsHDK® is available in multilayer valved paper bags which contain 10 kg of product. The bags are delivered on palettes which are shrink-wrapped with a polyethylene foil to protect the HDK® against moisture. This allows the product to be stored without any moisture uptake. If the shrink foil is damaged or single bags are removed, care must be taken to protect the remaining bags/individual bags against moisture by either wrapping in plastic or other appropriate measures.

•Palletized and shrink-wrapped for good product protection, storage and handling

•Three-ply paper for added strength•Bags are disposable

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EXPERTISE AND SERVICE NETWORK ON FIVE CONTINENTS

All figures are based on fiscal 2011.

• Sales and production sites, plus 20 technical centers, ensure you a local presence worldwide.

AUSWAHL EUROPA

WACKER is one of the world’s leading and most research-intensive chemical companies, with total sales of €4.91 billion. Products range from silicones, binders and polymer additives for diverse industrial sectors to bio-engineered pharmaceutical actives and hyperpure silicon for semiconductor and solar applications. As a technology leader focusing on sustain-ability, WACKER promotes products and ideas that offer a high value-added potential to ensure that current and future generations enjoy a better quality of life based on energy effi ciency and protection

of the climate and environment. Spanning the globe with five business divisions, operating 25 production sites, WACKER is currently active in over 100 countries. The Group maintains subsidiaries and sales offi ces in 29 countries across Europe, the Americas and Asia – including a solidly established presence in China. With a workforce of 17,200, WACKER sees itself as a reliable innovation partner that develops trailblazing solutions for, and in collaboration with, its customers. WACKER also helps them boost their own success. Our technical centers employ local

specialists who assist customers world-wide in the development of products tailored to regional demands, supporting them during every stage of their complex production processes, if required.WACKER e-solutions are online services provided via our customer portal and as integrated process solutions. Our customers and business partners thus benefi t from comprehensive information and reliable service to enable projects and orders to be handled fast, reliably and highly effi ciently.

Visit us anywhere, anytime around the world at: www.wacker.com

double_A4_e_europa_020412.indd 1-2 03.04.12 14:54

EXPERTISE AND SERVICE NETWORK ON FIVE CONTINENTS

All figures are based on fiscal 2011.

• Sales and production sites, plus 20 technical centers, ensure you a local presence worldwide.

AUSWAHL EUROPA

WACKER is one of the world’s leading and most research-intensive chemical companies, with total sales of €4.91 billion. Products range from silicones, binders and polymer additives for diverse industrial sectors to bio-engineered pharmaceutical actives and hyperpure silicon for semiconductor and solar applications. As a technology leader focusing on sustain-ability, WACKER promotes products and ideas that offer a high value-added potential to ensure that current and future generations enjoy a better quality of life based on energy effi ciency and protection

of the climate and environment. Spanning the globe with five business divisions, operating 25 production sites, WACKER is currently active in over 100 countries. The Group maintains subsidiaries and sales offi ces in 29 countries across Europe, the Americas and Asia – including a solidly established presence in China. With a workforce of 17,200, WACKER sees itself as a reliable innovation partner that develops trailblazing solutions for, and in collaboration with, its customers. WACKER also helps them boost their own success. Our technical centers employ local

specialists who assist customers world-wide in the development of products tailored to regional demands, supporting them during every stage of their complex production processes, if required.WACKER e-solutions are online services provided via our customer portal and as integrated process solutions. Our customers and business partners thus benefi t from comprehensive information and reliable service to enable projects and orders to be handled fast, reliably and highly effi ciently.

Visit us anywhere, anytime around the world at: www.wacker.com

double_A4_e_europa_020412.indd 1-2 03.04.12 14:54

wacker Chemie agHanns-Seidel-Platz 481737 München, GermanyTel. +49 89 6279-1741 info@wacker.com

www.wacker.com

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The data presented in this brochure are in accordance with the present state of our knowledge, but do not absolve the user from carefully checking all supplies immediately upon receipt. We reserve the right to alter product constants with the scope of technical progress or new developments. The information given in this brochure should be checked by preliminary trials because of conditions during processing over which we have no control, especially where other companies’ raw materials are also being used. The information provided by us does not absolve the user from the obligation of investigating the possibility of infringement of third parties’ rights and, if necessary, clarifying the position. Recommendations for use do not constitute a warranty, either express or implied, of the fitness or suitability of the product for a particular purpose.