Pharma & Healthcare News November 2012 by Alsiano A/S

Pharma & Healthcare News Alsiano No. 16 • November 2012

Contents AEROPERL® 300 Pharma a versatile carrier for liquid low solubility AP ....................1 New natural solution for skin moisturisation and beauty .....................................3 Beautify your lilfe!..................4 Synergized® Berry PowderTM. .5 Innovative injectable excipients ................................6 SEDOX® - plantain extract.......7 The Alsiano Healthcare team ........................................8

AEROPERL® 300 Pharma - a versatile carrier for liquid or low solubility API AEROPERL® 300 Pharma is a granulated form of colloidal silicon dioxide that enables incorporation of liquids into solid dosage forms and may assist in increasing bioavailability of low solubility APIs By Evonik AEROSIL® 300 Pharma is a high purity amorphous anhydrous colloidal silicon dioxide for use in pharmaceutical products. Unlike the well known AEROSIL® Pharma glidants, AEROPERL® 300 Pharma consists of bead-like mesoporous granules with a particle size of 30-40 μm on average. The high specific surface area of 300 m2/g, coupled with the mesopore volume of approx. 1.6 ml/g makes AEROPERL® 300 Pharma a versatile and highly absorptive carrier. Advantages of AEROPERL® 300 Pharma include: High tapped density and nearly spherical shape: AEROPERL® 300 Pharma is easy to handle, even when loaded with more than its weight in liquid. Hydrophilic nature: AEROPERL® 300 Pharma is an efficient desiccant. For example, AEROPERL® 300 Pharma may be used in cost efficient

Publisher: Alsiano A/S Circulation: 600 copies Editor-in-chief: Anders Hager Coordinator, text, lay-out: Dorthe Andersson Pharma & Healthcare News is published twice a year and distributed to customers and other interested parties. Reproduction of articles appearing in Pharma & Healthcare News requires prior consent of the author. Alsiano is not responsible for the content of articles written by external authors.

moisture activated dry granulation (MADG) processes to assist in absorbing and distributing the small amount of water used. High absorption capacity and high surface area: AEROPERL® 300 Pharma may help to increasie the solubility of poorly soluble APIs. AEROPERL® may also assist to avoid costly and time consuming API crystallisation. AEROPERL® 300 Pharma is manufactured and packaged in a closed production system according to GMP guidelines established for bulk pharmaceutical excipients by the International Excipients Council (IPEC/GMP) and fulfils requirements of Ph. Eur. as well as USP/ NF. Due to its high bulk density, AEROPERL® 300 Pharma does not fulfil the “volume test” of the JP, but complies with all other JP parameters. (continues on page 2 >>)

Pharma & Healthcare News Food News

No.116• •February November2004 2012 No. and hydrophobic, as well as granulated types. In addition to AEROPERL®300 Pharma, Evonik’s range of colloidal silicon dioxide for pharmaceuticals comprises

AEROPERL® 300 Pharma

>> Applications • Carrier for liquid and pasty (active) ingredients, converting these ingredients into free-flowing powders • Adsorbent • Desiccant in moisture activated dry granulation, supporting pharmaceutical producers to save costs in wet granulation processes Properties • Dust-free and easy to handle • High purity, very low metal contaminations • Excellent flow both loaded and unloaded

AEROSIL® Pharma colloidal silicon dioxide for pharmaceuticals Cost-effective and reliable manufacturing methods are an absolute must for today’s pharmaceutical industry. This is just one reason why AEROSIL® colloidal silicon dioxide has become one of the most important and frequently used pharmaceutical excipients. Improving flow properties of starting materials required for modern tablet and capsule manufacture is just one example of the advantages gained by using AEROSIL® fumed silica. It can also considerably improve the manufacturing as well as properties of many other drug forms. AEROSIL® colloidal silicon dioxide has been used in the pharmaceutical industry for almost 50 years. Since the introduction of AEROSIL® 200 Pharma, Evonik has expanded its pharma product portfolio with special pharmaceutical grades available in different surface areas, hydrophilic

AEROSIL® 200 Pharma High purity amorphous anhydrous colloidal silicon dioxide for use in pharmaceutical products (tested according to USP/NF, Ph. Eur. and JP). For all types of dosage forms. • Free flow and anti-caking agent to improve powder properties • Reduce weight variability in direct compression tabletting processes • Improves tablet properties such as hardness and friability • Rheology additive, thickens liquids and renders them thixotropic • Improves distribution of active pharmaceutical ingredients AEROSIL® 200 VV Pharma Compacted version of AEROSIL® 200 Pharma that can be used in solid dosage forms. AEROSIL® 200 VV Pharma has the same high purity as the noncompacted version but requires considerably less space on storage. tested according to USP/NF and Ph. Eur. • Good handling and application properties due to densification • Reduced dust generation • Free flow and anti caking agent to improve powder properties • Improves the mechanical stability and weight consistency of solid dosage forms AEROSIL® 300 Pharma High purity amorphous anhydrous colloidal silicon dioxide for use in pharmaceutical products with a very high specific surface area (tested according to USP/NF, Ph. Eur. Monograph 0434 and JP). Especially suitable for semi-solid and liquid dosage forms. • Used as viscosity increasing agent to thicken and thixotropize liquids • Improves storage and temperature stability of semi-solid and liquid dosage forms

Alsiano Alsiano • Improves distribution of active pharmaceutical ingredients • Free flow and anti-caking agent to improve powder properties AEROSIL® R 972 Pharma Hydrophobic colloidal silicon dioxide of high purity. (tested according to Ph. Eur. and USP/NF monographs). Especially suitable for solid dosage forms and emulsions. • Easy to mix glidant for improving powder flow, especially suitable for very hygroscopic and/or cohesive powders • Rheology additive for thickening of polar pharmaceutical oils to create thixotropic gels. • Stablilises dispersions of other insoluble solids in oils, thereby increasing storage stability • May be used to adjust release behavior of active ingredients All our AEROSIL® and AEROPERL® pharma grades are manufactured and packaged in a closed production system according to GMP guidelines established for bulk pharmaceutical excipients by the International Excipients Council (IPEC/GMP). Article 376

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New natural solution for skin moisturisation and beauty CERAMOSIDESTM from Seppic is a new range of ingredients for nutri-cosmetics with clinically proven and visible results in just 15 days

Superior and clinically proven efficacy CERAMOSIDES™ has been tested in several studies, including in vitro tests and human clinical studies. Two clinical studies have demonstrated • superior efficacy on skin moisturising and anti-ageing • quick action - visible results within 2 weeks • results perceived by subject • low level of use A double blind clinical study on 60 women has been conducted, using well-recognised methods like corneometry, trans-epidermal waterloss (TEWL), skin elasticity and profilo-

After 15 days CERAMOSIDES™ significantly improved skin moisturisation index by 23% versus placebo and by 36% versus placebo after 60 days. The subjects having dry skin at the beginning of the study had a very moisturized skin after 60 days. These results can be correlated with the strong reduction of trans-epidermal water loss that could be observed after 15 days (-16% versus placebo) and after 60 days (-19% versus placebo) - see figure. Significant results were also seen on the reduction of wrinkles, which were reduced by 8% (versus placebo) after 15 days and by 19% (versus placebo)

CERAMOSIDES™ - a product you can trust • all natural dietary ingredient • 100% wheat from European origin, manufactured in France • no additives or GMOs • guaranteed gluten-free • contains rare lipids extracted from wheat flour selected to guarantee the best quality

Skin moisturisation (Corneometry) Moisturisation index (C.u.)

CERAMOSIDES™ is a patented extract containing a natural complex of ceramides and digalactosyl diglycerides (DGDG). This complex has been selected for its strong efficacy on skin moisturisation, allowing a rapid action with a low daily dose. As CERAMOSIDES™ contains polar lipids, particularly ceramides, it provides an interesting source for the organism to restore ceramides deficiency in the stratum corneum.

metry measurements. The subjects were selected with carefully chosen inclusion criteria, including a dry skin condition. During 60 days, the subjects ingested daily a capsule containing either a placebo or CERAMOSIDES™ in oil form (70 mg/ day) or in powder form (30 mg / day). Parameters concerning skin moisturisation and aspects were recorded at the beginning of the study, after 15 days, after 30 days and after 60 days. All data were analysed using recognised statistical analysis methods.

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Trans-epidermal water loss (TEWL) TEWL (g/h/m2)

By Claire Notin, Seppic

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CERAMOSIDESTM powder CERAMOSIDESTM oil Placebo

after 60 days. The anti-aging action of CERAMOSIDES™ was also shown by a significant increase in skin elasticity. In addition, the appearance of the skin was improved: the skin was significantly smoother and significantly less rough. These results are all the more interesting as they were extremely quick (only 15 days) and perceived by the subject. (continues on page 4 >>)

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Beautify your life! Brand new pearl gloss product from Kolb By Kolb KOLB offers to make your life more beautiful with SYMPATENSTM-PEARL. The new product provides you with the listed benefits in your personal care formulations: Boost to beauty Provides shampoos, shower gels, hand soaps and hand liquid soaps with a luxurious, pearlescent shine. Easy to process Processing at room temperature. A pearlescent effect is visible at 0.5% concentrations. Increased product concentration gives increased effect. Recommended concentration is 1-3%.

>> CERAMOSIDES™ mode of action Orally ingested, ceramides are partially digested and components from these ceramides reach the skin where they participate in the synthesis of new ceramides and consequently contribute to skin moisturisation. This was shown using radio-labeled ceramides in rats (UEDA 2009). DGDG of this lipid complex contribute to the specific efficiency of CERAMOSIDES™ by improving ceramide metabolism and absorption. This synergistic effect among lipids in the complex increases the power of CERAMOSIDES™. Thanks to this patented innovation, CERAMOSIDES™ offers quick visible results at a low daily dose. A unique solution for a variety of formulations and applications CERAMOSIDES™ provides strong complementary actions and creates a synergistic effect bringing its unique results on the skin within 15 days. CERAMOSIDES™ is available in two different forms, as an oil or as an hydro-dispersible powder. This innovative natural ingredient can be incorporated in any nutri-cosmetics formu-

Ready to use Can be used directly in existing as well as in new product formulations. SYMPATENSTM-PEARL extends Kolb`s personal care portfolio of established top basics • Sympatens-TRH/400 (INCI: PEG-40 Hydrogenated Castor oil) • Sympatens- GMC/070 (INCI: PEG-7 Glyceryl Cocoate) • Kotilen-L/1 (INCI: Polysorbate 80) • Kotilen-O/1 VL (INCI: Polysorbate 20)

lations like soft gel and hard-shell capsules, tablets, sticks and beverages to improve skin moisturisation, to reduce skin roughness, improve skin elasticity and to offer an anti-aging effect. CERAMOSIDES™ can be used for moisturising products • anti-ageing products • moisturising UV products • sensitive skin products • eye dryness/vaginal dryness products

and top performers: • Sympatens-O/2500 G (INCI: Sorbitan Stearate (and) Methyl Glucose Sesquistearate) • Sympatens-W/4500 (Sorbitan Oleate (and) Polyglyceryl-3 Polyricinoleate) Article 377

Because of the oral delivery pathway CERAMOSIDES™ provides global benefits to the skin - including both face and body - in just one easy daily step. CERAMOSIDES™ is a trendy solution which perfectly matches the demand of today’s modern consumers! Article 378 LAFFORGUE, Epidermal lipids and the stratum corneum,Réalités Thérapeutiques en Dermato-Vénérologie, 2008 ;179 : 2 UEDA, Drug Metab. Pharmacokinet, 2009 ; 24 (2): 180–184 2 JUNGERSTED JM et al. Lipids and skin barrier function – a clinical perspective. Contact Dermatitis, 2008 ; 58 : 255-62 1

Ceramides, a key role in skin moisturisation The principal function of the skin is the role as barrier between the inner and the outer. The skin is a barrier to different things like water and electrolytes loss and to avoiding desiccation of the organism. The skin consists of three layers: hypodermis, dermis and epidermis. The function of water barrier is assured by the outer part of epidermis, the stratum corneum, which is the most external layer of the skin1. The stratum corneum can be compared to a “brick wall” structure composed of specific cells (keratinocytes

differentiated into corneocytes) and an intercellular matrix contain ing lipids. The lipidic composition of the stratum corneum can explain the function of water barrier. The most of these lipids are ceramides or glycospingolipids, and that explains why ceramides can be considered as key factors in the skin protection against water loss1. Studies have shown that correlations exist between the decrease of ceramides content in the stratum corneum and physiological changes such as skin dryness, ageing, atopic dermatitis2.

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Synergized® Berry PowerTM Berry PowerTM contains a highly targeted selection of the most potent berries offering the greatest diversities of goodies By Synergy Production Laboratories The certified organic, freeze-dried Berry Power™ blend from Synergy Production Laboratories contains the whole fruits and juices of twelve of the most potent and medically compelling berries available. All of our berries are organically grown, hand harvested, cold temperature-processed and then precisely formulated, blended, and vacuum packaged at our award-winning, certified organic and kosher facility. The result, Berry PowerTM, comprises the true "superfruits," which research reveals to be so much more than just "antioxidantrich." Customers are no longer just interested in plain old antioxidant claims; they are looking for specific health effects and a change in certain health parameters. Medical research on the various berries in Berry PowerTM reveals a mountain of positive studies showing their multifaceted health benefits, from cardiovascular protection to eye

Synergized® Berry Power™ Synergy Production Laboratories’ best-selling certified organic, proprietary powdered blend of 12 fresh freeze-dried berries (including whole berries, seeds and juice) represents the purest, most comprehensive and potent berry blend powder in the industry. • • • • • • • • • • • •

Wild Bilberry Black Currant Aronia Wild Lingonberry Pomegranate Wild Blueberry Concord Grape Sour Cherry Wild Elderberry Wild Cranberry Red Raspberry Black Raspberry

health to inflammation prevention and much more. And each berry in Berry PowerTM has its own special blueprint, so to speak, with different health-promoting qualities and unique types of phytochemicals including flavonoids, quercetin, anthocyanins, catechins, salicylic acid, chlorogenic acid, ellagic acid and many others. A perusal of the studies indicates that many of these compounds have been shown to play a significant and positive role in the following: • Cellular DNA protection • Detoxifying toxins through Phase 2 enzymes • Estrogen-balancing metabolism • Digestive, respiratory, skin cancer protection • Allergy modulation • Memory and cognition enhancement • Immune function/regulation • Conserving and recycling of Vitamin C • Vascular support • Heart disease reduction • Stroke risk reduction • Eye health (including macular degeneration) And that’s just the short list. See the potential? Variety is the ‘health’ of Life Research shows that the powerful health benefits of berries work synergistically and are far more effective when a full spectrum of fruits and berries is consumed all together as opposed to single berries, berry isolates, or berry blends with just a few ingredients. In a very recent study published in Nutrition, Metabolism and Cardiovascular Disease in August 2012, researchers discovered the definite link between ongoing anthocyanin consumption from fruits and vegetables

and reduction of inflammation associated with disease processes. Of great interest, results also indicated that the anthocyanins had synergistic effects, meaning that the sum of the effects was greater than the effects of the individual anthocyanins. “Hence, incorporating plant-based foods rich in different anthocyanin compounds in the diet is likely to be more beneficial than consuming a single anthocyanin supplement,” researchers added. Synergy Production Laboratories created Berry Power™ to pack a strong phytonutrient punch with a full rainbow of the most beneficial, scientifically noteworthy phytochemicals available. The complexity of the formula reflects the complexity of phytonutrients that exist in nature. Far from a random assortment of berries, Berry Power contains a highly targeted selection of the most potent berries offering the greatest diversity of goodies. (continues on page 6 >>)

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Innovative injectable excipients Seppic strengthens its position as the world leader in injectable excipients by dedicating an entity to the development of new innovative products By SEPPIC SEPPIC, member of Air Liquide Healthcare, is a global manufacturer of innovative speciality ingredients for pharmaceutical and healthcare applications as well as the cosmetic, nutrition and industrial markets. Among all these businesses, SEPPIC has dedicated an entity to the development of innovative injectable excipients, the mission being to deliver a healthier future. SEPPIC provides injectable excipients produced under the most stringent quality standards (GMP part II). By following these standards, SEPPIC ensures the quality of its customer’s drug products. High performance excipients for pharmaceuticals For the past thirty years, SEPPIC has been supplying excipients to the pharmaceutical industry. SEPPIC has developed a specific range of surfactants, produced under GMP Part II guidelines,

and complying with the most current Pharmacopoeias (EP /USP-NF/ JP). These surfactants, well known for their solubilising and/or emulsifying properties, are dedicated to parenteral and ocular formulations. The products are marketed under the trade names of Montane™ PPI for the sorbitan esters range and Montanox™ PPI for the polysorbates range. Leader in innovation SEPPIC constantly innovates in order to meet its customer’s needs in terms of quality, regulatory issues and formulation. As a world leader in injectable excipients, SEPPIC continues to strongly invest in R&D in order to propose better solutions for a better health. Among recent innovations, Sepiclear™ PPI is a new range of powerful solubilisers based on lipoaminoacid and dedicated to poorly soluble actives for injectable application.

>> True superfruits still trending up Market trends indicate that consumers are seeking real fruit and vegetable formulas containing tried and true ingredients that are organic, whole and natural rather than engineered or isolated.

Excellent customer service and technical support Seppic’s team of experts in chemical synthesis, formulation, analysis is available to assist you throughout your drug development process. They provide customised services from formulation through product launch and guarantee full confidentiality for each project. Article 379 Cocoa

Application suggestions: • Superfood formulas • Fruit/berry powders • Beverages and natural energy drinks • Nutrition bars • Whole food based capsules/ tablets • Antioxidant formulas • Anti-aging formulas • Skin care formulas • Cardiovascular formulas

Synergy Production Laboratories has taken out all the guesswork by expertly creating a full spectrum, potent and effective organic berry and fruit formula that captures all the beneficial phytonutrients and whole food benefits that health-oriented customers are actively seeking. And Hibiscus it's yummy too! Article 380

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SEDOX® – plantain extract Re-discover the ancient herb with the many good properties By Epo Srl

activation of anti-oxidative enzymes, by suppressing the activation of NDkB17 pathway and by inhibiting the biosynthesis of other pro-inflammatory factors. In a recent study1, an etha-nolic spissum extract of plantain was examined in vitro for antispasmodic activity. Results showed that luteolin and verbascoside (CPG) inhibited the contractions of the guinea-pig ileum induced by acetylcholine. Anti-inflammatory properties of CPGs have been proved in animal studies and in vitro2,3.

SEDOX® is an extract of plantain (Plantago lanceolata L.) standardised in verbascoside and manufactured by ethanolic extraction. Plantain is well suited for cough relieving products as in Europe it has traditionally been used for medicinal purposes especially for treatment of cough, asthma, whooping cough, and bronchitis. Plantain has been approved by the German Commission E for the treatment of the flogistic conditions of the upper respiratory airways and is today a commonly used extract in natural remedies in Germany. Furthermore, plantain extract can also be applied in different final pro-ducts from nutritional supplements to cosmetics thanks to its excellent antioxidant properties. Plantain contains the following active components:

Cough soothing, expectorant & antibacterial Mucilage contributes to the lenitive and cough soothing properties of plantain. Many other mucilage extracts like marshmallow, mallow, Iceland moss, linden, etc. are also used to soothe inflammatory conditions of mouth and throat mucosae, displaying a demulcent and protective action.

• Mucilage – polysaccharides • Iridoids – bicyclic monoterpenes, mainly aucubin and catalpol • Tannins and polyphenols – e.g. caffeoyl phenylethanoid glycosides (CPG incl. verbascoside) • Flavonoids - luteolin

Antioxidant & free radical scavenging The antioxidant and free radical scavenging properties of plantain are due both to luteolin1 and to CBGs, especially to verbascoside4. These properties have been tested on SEDOX® at Ambrosialab Srl by different analytical methods, such as the FRAP, the DPPH radical and the ORAC assays. In all tests, SEDOX® showed a good antioxidant and ... (continues on p. 8 >>)

SEDOX® offers the following properties: Anti-inflammatory & antispasmodic The anti-inflammatory and antispasmodic properties depend on flavonoids and CPGs. Luteolin displays specific anti-inflammatory effects by

The antibacterial action of plantain appears to be due to aucubigenin, the iridoid agylcone obtained by enzymatic hydrolysis during the drying process of plantain leaves. A few clinical trials have been carried out to support the anti-inflammatory, broncholytic and expectorant properties of plantain. Their positive results confirm the traditional use.

About EPO EPO, established in 1933, is an Italian manufacturer of a wide range of plant extracts including Bilberry 1%, Lemon balm 2%, Iceland moss ¼ and Butcher’s broom 5%. The product range comprises dry powdered extracts, fluid extracts, mother tinctures and glycolic extracts. The plants selected by EPO come from cultivations in complete harmony with nature and must pass an accurate examination in their quality control laboratory to check their botanical identification, their quali-quantitative composition and the absence of contaminants. All the extractive processes, concentration and drying used by EPO are set up and optimised in such a way as to fully respect the integrity of the phyto complex. EPO’s entire production cycle is validated and characterised by the use of the most modern technology available in order to ensure a minimum impact on the environment. A dynamic and efficient service, in combination with the high technical level of their products, makes EPO not only a trustworthy source, but indeed a reference point in the botanical extracts sector. EPO is UNI EN 9001-2008 certified.

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The Alsiano Healthcare team Pharmaceuticals - cosmetics health & nutrition

Key accounts

Pharmaceuticals - cosmetics health & nutrition

Anders Hager

Henrik A. Petersen

Annette Strarup

M.Sc. Chem. Sales Director

M.Sc. Pharm. Senior area sales manager

B.Sc. (Hons.) Chem. Eng. Area sales manager

E-mail: ahg@alsiano.com Tel. dir.: +45 8230 0026 Mobile: +45 2618 8545

E-mail: hap@alsiano.com Tel. dir.: +45 8230 0009 Mobile: +45 2067 1231

E-mail: ask@alsiano.com Tel. dir.: +45 8230 0049 Mobile: +45 2270 1015

Pharmaceuticals - cosmetics health & nutrition

Sales support

Lene Aarøe Nissen

Malene Rask Harder

Signe Mørck

B. Chem. Eng. Area sales manager

Sales assistant

E-mail: mrh@alsiano.com Tel. dir.: +45 8230 0007

E-mail: sm@alsiano.com Tel. dir.: +45 8230 0042

leave

rnity E-mail: lan@alsiano.com mate n o Tel. dir.: +45 8230 0025 Mobile: +45 2270 1002

Logistics

Quality Lene Baldasano del Valle

Susse Liff Hansen

Logistics manager

Quality manager

E-mail: lb@alsiano.com Tel. dir.: +45 8230 0015

>> radical scavenging effect (4000 units ORAC/ 100g) with a double mechanism of action, reducing and radical quenching, and a good degree of homogeneity among the results on different batches. The total polyphenol content has been determined by Folin-Ciocalteau assay with the same good results.

E-mail: slh@alsiano.com Tel. dir.: +45 8230 0017

• Nutritional supplements – lozenges, mixtures, pastilles • Natural remedies – tinctures, pastilles • Cosmetics – anti-ageing cream, cream for sensitive skin, eye gel References Sellinger et al., Planta Medica, 2008, 14, 1667-77 Murai et al., Planta Medica, 1995, 61, 479-480 Vigo et al., Journal of Phamacy and Pharmacology, 2005, 57-3, 383-391) 4 Chiou WF et al., Journal of pharmacy and pharmacology, 2004, 56-6, 743-748 1

Applications Plantain’s many properties including anti-inflammatory, expectorant and antioxidant makes it well suited for a wide range of products including:

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