Pharmanews November 2014

Pharma & Healthcare News Alsiano No. 20 • November 2014

Contents Ajinomoto expands its cooperation with Alsiano ......1 Curcumin with superior bioavailability..........................2 KiOFiber - the multitasking fibre..........................................3 Jost Chemical: your partner in pharmaceutical & biotech applications . .............4 Excipients: Calcium phosphates..............................5 Formulating very high protein drinks..........................6 Beta-carotene from natural source ........................7 Pharmaceutical excipients present in your daily life . ......8 Reduce the cadmium level of your finished products ......8 Drug delivery technologies for food, feed and pharmaceutical applications ..............9 The Alsiano Healthcare team ......................................10

Ajinomoto expands its cooperation with Alsiano Alsiano is new distributor of Ajinomoto amino acids for the pharmaceutical and healthcare industries in Sweden and Norway We are pleased to announce that Ajinomoto has appointed Alsiano as their distributor in Sweden and Norway. Alsiano has represented Ajinomoto on the Danish market for many years, and in future Alsiano will thus be able also to introduce Ajinomoto’s line of high quality amino acids to the pharmaceutical and healthcare industries in Sweden and Norway.

Ajinomoto Ajinomoto is a leading manufacturer of amino acids and the first company in the world to produce amino acid crystals for infusions, enteral nutrition products and pharmaceutical ingredients. The areas of amino acid applications have been expanded to food, beverage and toiletry products to add nutritional and physiological value to the products. Ajinomoto provides both a full range of the Ajinomoto brand amino acids together with custom blends tailored to the

Publisher: Alsiano A/S Circulation: 550 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.

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needs of customers for pharmaceutical, food, beverage and cosmetics applications. In addition to the excellent quality, which is to be expected from the world’s leading producer of amino acids, the company offers its customers technical and regulatory assistance which is essential to commercialise products containing amino acids.

Flexible packaging sizes Ajinomoto strives to supply the highest quality products and services based on reliable and flexible production. Therefore Ajinomoto is offering amino acids in 10 kg and 1 kg packing sizes.

Yutaka Morota, Sales & Marketing Manager, Amino Acids, AminoScience Division Europe, has the following comments to this change of organisation, “In our experience, working with the pharmaceutical (continues on page 2 >>)

Pharma & Healthcare News Food News

No.120• •February November2004 2014 No.

Alsiano Alsiano

Curcumin with superior bioavailability The unique NovaSOL® technology transforms curcumin into its most bioavailable form making it possible to create highly potent, small-dose products

By Frutarom While the beneficial properties of curcumin and its mechanism of action have been profoundly studied, its limited bioavailability is a major issue. Because of the low absorption of water insoluble compounds, a standard extract needs to be used in very high dosage for efficacy. A unique technology that makes these compounds highly soluble has solved this problem.

The NovaSOL® solubilisation technology gives curcumin unique properties which result in a faster absorption, a very high bioavailability.and longer lasting effect.

A human clinical trial shows the superior bioavailability of NovaSOL® Curcumin compared to a standard extract. This very stable, highly bioavailable solubilisate enhances the effect and the multiple health benefits of curcumin and is effective at much lower dosages. The material results in a clear yellow solution in both water and oil due to its unique micelle structure.

Applications NovaSOL® Curcumin available from Frutarom can be used in a broad variety of applications and products such

>>

as beverages or dietary supplements, especially soft gel capsules. Furthermore, the solubilisates are proven to be very stable and are ready for production use.

Dosage: 670 mg/day – equivalent to approx. 8 g standard curcumin 95%.

Article 403

NovaSOL® Curcumin • Curcuminoids: min. 6% • Liquid curcumin solubilisate

Curcumin The dried, powdered root of the turmeric plant has a long history of use in Ayurvedic treatment of various inflammatory conditions. Curcumin is well known for its potent antioxidant and anti-inflammatory properties and can play a vital role in the prevention of chronic inflammation which is linked to several conditions regarding joint health, brain health, gut and cardiovascular health.

• Unique solution with proprietary technology • Fully water and fat soluble • Clear coloured dissolution • High bioavailability • Supported by clinical data

industry requires, among other things, long term commitment, technical competence and a thorough understanding of the development process in the industry. By appointing Alsiano in Sweden and Norway, we strongly believe that Ajinomoto shall be able to meet these demands.”

Anders Hager, sales director of Alsiano, is pleased with Ajinomoto’s decision and states, “We are very proud that Ajinomoto has chosen us to

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represent them in Sweden and Norway and we consider this decision a token of Ajinomoto’s satisfaction with the work we have performed so far within the Danish pharma and healthcare industry. For Alsiano, the addition of Ajinomoto’s amino acids will make our product portfolio visà-vis our Swedish and Norwegian customers more complete and thus more attractive”.

Article 404

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Alsiano

KiOFiber - the multitasking fibre Digestive health: KitoZyme launches a new unique and natural fibre supplement product based on the patented and clinically proven KiOtransine® technology KiOFiber is a new fibre supplement from KitoZyme based on the unique KiOtransine® - non-animal ChitinGlucan. Chitin-Glucan is a novel patented ingredient of fungal origin that combines two types of polysaccharide chains that are linked covalently in a three dimensional structure.

Intended for use as a daily fibre supplement, KiOFiber features the benefits of both soluble and insoluble fibres. Thanks to its gelling properties, KiOFiber helps maintain a healthy and balanced gut microbiota and promotes digestive wellness leading to an overall feeling of wellbeing.

In addition, KiOFiber supports clean healthy arteries and reduces oxidised LDL-cholesterol.

KiOFiber is particularly well tolerated and has also shown good results on IBS patients proven by clinical trials - see the figure and table. Furthermore, it is appropriate for use in Kosher, Halal and vegetarian products/ diets.

The recommended dosage is 1.5 g per serving taken 3 times a day.

Clinical study in overweight and obese subjects, Pharmascan. Efficacy evaluation IBS subjects, evolution of the frequency ofintestinal symptoms during treatment

Mean change of frequency

By KitoZyme

* p<0.05

% of subjects who “sometimes to never” felt:

D0

D56

Abdominal pain

32%

95%

Bloating

26%

95%

Flatulence

26%

71%

Solutions suited to your needs KitoZyme offers KiOFiber as finished products in different galenical forms: capsules, film coated tablets, sticks and powder, and as ingredient for integration into your recipes (KiOFiber is heat resistant). KiOFiber comes in the following different tastes: • Neutral • Orange • Lemon • Pink grape

Proven safety & efficacy The efficacy of KioFiber has been proven by in vitro and in vivo tests and Gold Standard clinical trials.

The Chitin-Glucan is a natural, selfaffirmed GRAS source and has EU Commission approval as a novel food ingredient. KioFiber is manufactured in accordance with ISO and HACCP guidelines.

Article 405

• Helps relieve occasional constipation, bloating and abdominal pain • Supports clean, healthy arteries • Supports digestive health – improves transit • Reduces oxidised LDL-cholesterol levels

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Jost Chemical: your partner in pharmaceutical & biotech applications High purity inorganic salts meeting stringent quality requirements and guaranteeing full traceability and lot-to-lot consistency

By Jost Chemical

Mitigate Your Risk

Jost manufactures inorganic salts used as biological buffers and process intermediates by the pharmaceutical, biotech and diagnostic industries. The products are used in API synthesis, vaccine manufacturing, fermentation processes and cell culture media.

• US FDA registered manufacturing site

Jost has stringent quality requirements ensuring that they provide customers with high purity, lot-to-lot consistent products that meet your specifications every time. All products are manufactured and fully tested in house.

• Audited regularly by the FDA and customers in the pharmaceutical and biotech industries

Technical support – product solutions High purity - Make sure to use a high purity chemical salt: Jost’s mineral salts are characterised by low levels of vagrant metals (tested using ICP-MS).

Free-flowing - Some chemical salts have a high tendency to agglomerate prior to use, and caking or hardening of inorganic salts causes bottlenecks in your production. Jost Chemical manufactures free-flowing chemical salts without the use of flow agents.

A dry granulation process is used to manufacture free-flowing granules which will improve your efficiency.

• 17,000 m2 facilities • Operates under ICH Q7 bulk pharmaceutical cGMPs

• Products are manufactured to meet USP/EP/BP/JP/ACS and multi-compendial requirements • BSE/TSE free products

Examples of inorganic salts for pharmaceuticals and biotech applications • Ammonium Phosphate Monobasic ACS • Ammonium Phosphate Dibasic NF/ACS • Ammonium Sulfate NF/ACS • Cupric Sulfate Pentahydrate USP • Ferrous Ammonium Sulfate Purified

Traceability Jost Chemical's adherence to GMP manufacturing assures that all finished goods are fully traceable "backwards" to the raw materials and "forwards" into the final packaging and ship-to location for every container comprising the production lot.

Quality documentation and support Jost understands your need for immediate and detailed responses to inquiries for product and technical information. Jost will work with you to meet your specific product requirement and to develop a DMF, ASMF and CEP. Custom packaging Jost offers customised packaging solutions including fiber-free drums and super sacks.

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• Manganese Sulfate Monohydrate USP/EP/ACS • Potassium Carbonate ACS • Potassium Phosphate Monobasic NF/EP/BP/ACS • Potassium Phosphate Dibasic USP/ACS • Potassium Sulfate EP/ACS • Sodium Acetate Trihydrate USP/EP • Sodium Caprylate NF/EP • Sodium Carbonate Anhydrous NF/EP/JP/ACS • Sodium Carbonate Monohydrate NF/ACS • Sodium Phosphate Monobasic Monohydrate USP/BP/ACS • Sodium Phosphate Dibasic Anhydrous USP/EP/ACS • Sodium Phosphate Dibasic Heptahydrate USP/ACS • Sodium Phosphate Tribasic Dodecahydrate ACS • Sodium Sulfate Anhydrous USP/ACS

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Excipients: Calcium phosphates Together with Canberra Chemicals, Alsiano offers a line of calcium phosphates at competitive prices Canberra Chemicals, founded in 1975, is an India-based manufacturer of calcium phosphates with manufacturing facilities that comprise state-of-the-art equipment and a fully equipped laboratory operated by a highly skilled staff.

Canberra manufactures the following types of calcium salts of phosphoric acid: • •

Dibasic calcium phosphate dihydrate/anhydrous Tribasic calcium phosphate

Dibasic calcium phosphate The unmilled granules of dibasic calcium phosphate have excellent flow properties and an ideal compressibility index with a nearly 70% retention at 100 ASTM and fines below 5% at 325 ASTM. This makes it ideal for direct compression tableting formulations. For applications exceeding 45°C, the anhydrous form is preferred.

Tribasic calcium phosphate This is a bulky powder with an ideal Ca/P ratio of 2:1 for better bio-availability in calcium supplements. The crystalline powder is manufactured by a special process that gives it high porosity. This high porosity makes it ideal for application as an anticaking agent.

All Canberra phosphates conform to California Proposition 65 regarding lead and fluorine levels. It is also worth mentioning that for direct compression into tablets, Canberra can offer calcium phosphates with specific particle sizes tailored to the customer’s need.

Applications Canberra calcium phosphates are sold to pharmaceutical companies in India, USA, Western Europe, and other markets. The main scope of application includes: Pharmaceutical • Excipient in direct compression, wet granulation and tableting

• Calcium mineral supplement • Pharmaceutical acids in calcium phosphate preparation Food • Anticaking agent • Calcium mineral supplement Article 407

Canberra Chemicals phosphates • Pure white coloured products free of black particles • Free from fungi, bacteria and other biological impurities • Manufactured under rigid quality standards with strict adherence to GMP and fully tested for all parameters

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Formulating very high protein drinks Sports nutrition: PRODIET FLUID meets the challenge of producing a delicious high protein ready-to-drink beverage while maintaining fluidity similar to that of milk

By Ingredia When it comes to sports nutrition, more and more consumers do not look for efficacy only, but also pleasure and convenience. Ready-to-drink (RTD) beverages are very popular in sports, fitness and diet nutrition, and it is now possible to fulfil all of these expectations.

Many RTD protein beverages typically contain 7-8% standard protein on average formulated with milk protein isolate (MPI) or whey protein and have insipid texture and taste. Raising the protein content is not easy since it tends to thicken the beverage. In addition, most of the proteins used today on the market such as WPI are not heat stable.

PRODIET FLUID PRODIET FLUID from Ingredia is a high quality MPI in spray-dried powder form which contains more than 87% protein on dry matter. It is rich in micellar caseins - 92% compared to 80% in fresh milk. This ingredient allows you to develop successful endproducts by combining outstanding technological and nutritional functionalities.

With PRODIET FLUID, it is possible to reduce the high protein beverage viscosity by up to 88% compared to a similar MPI. Since PRODIET FLUID displays a lower viscosity than standard MPI in a high protein RTD beverage, it makes an increase of the protein content of up to 14% possible, while still maintaining a pleasant and fluid texture similar to that of milk.

Furthermore, the beverage will have a natural milky taste with no off-flavour.

It is very easy to implement PRODIET FLUID in any drink process since it does not require any specific steps or equipment. Moreover, drinks formulated with PRODIET FLUID can undergo UHT treatment for increased shelf life as it offers excellent stability to high temperatures.

High protein beverage concepts Ingredia has conceived a range of 8 original very high protein RTD beverages in line with market trends and consumer expectations. All 8 beverages at 250 ml contain 35g protein (14%). Here is an outline of some of the concepts:

TONE UP: dedicated to consumers willing to take care of their health combined with an active lifestyle.

Helps consumers increase their lean body mass and promotes overall wellness. (continues on page 7 >>)

PRODIET FLUID nutritional advantages • Superior native micellar casein with a chemical index > 120 • All-natural non-denaturated ingredient from fresh milk • Long release amino acids • Sustained feeling of satisfaction • Very rich in BCCA (branched chain amino acids)1,2 • High content of highly bio-available native micellar calcium • Possibility of health claims linked with its protein and calcium content • Clean label - labelled as Milk Protein Isolate (MPI) • Available in a lactose-free version

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Beta-carotene from natural source Vidya Herbs offers a broad range of natural carotenoids for tablets, hard capsules, soft gel and food colouring Vidya Herbs produces natural betacarotene, also known as NBC, from Dunaliella salina and Blakeslea trispora fungus through fermentation. The natural beta-carotene colour range varies from bright yellow over vivid orange to reddish brown in colour.

Vidya Herbs’ range of natural betacarotene is available in: • Micro encapsulated beadlets • DC grade powder • Cold water dispersible (CWD) • Emulsion & oil suspension

Beta-carotene can, for instance, be used in capsules for sun burn protection targeted persons who are sensitive to sun, for boosting skin health and as a natural vitamin supplement.

Beta-carotene Beta-carotene is a strongly coloured red-orange pigment abundant in plants and fruits. It is an organic compound and is chemically classified as a hydrocarbon and specifically as a terpenoid (isoprenoid), reflecting its derivation from isoprene units.

Carotene is the substance in carrots,

NATURAL BETA-CAROTENE

NATURAL MIXED CAROTENE

FORMULATION

APPLICATION

Powder

Tablet & hard capsules

5-30%

5-30%

Beadlets

Tablet & hard capsules

5-30%

5-30%

Oil suspension

Soft gel & food colouring

10-30%

10-30%

Emulsion

Soft gel & food colouring

1-10%

1-10%

SHAPE UP: Makes the consumer experience sustainable weight management. An increase of the protein content of a protein based diet is proven to be efficient4.

>> MUSCLE REPAIR: Studies show that

protein ingestion before sleep improves post-exercise overnight recovery3. This concept provides the consumer with night-long amino acids release to replenish the muscles while sleeping.

RECOVER: Provides the consumer with a dual action for muscle repair: fast acting amino acids from protein hydrolysates combined with a sustained AA release from micellar casein for a longer action. Contains also carbohydrates to provide energy.

Please contact Alsiano for more information about the concepts and Ingredia’s other concepts for RTD high protein beverages.

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pumpkins and sweet potatoes that colours them orange and is the most common form of carotene in plants.

When used as a food colouring agent, it has the e-number 160a. In nature, beta-carotene is a precursor (inactive form) to vitamin A via the action of beta-carotene 15,15’-monooxygenase.

It is deeply coloured, and as a hydrocarbon lacking functional groups, it is very lipophilic.

Article 408

References 1. Lewis J. James et al. Effect of milk protein addition to a carbohydrate-electrolyte rehydration solution ingested after exercise in the heat. British Journal of Nutrition. 2011 2. Antti Mero. Leucine Supplementation and Intensive training. Sport Med. 1999 3. Peter T. Res, B. Groen et al. Protein Ingestion before Sleep Improves Postexercise Overnight Recovery. Medicine & Science in Sports & Exercise, 2012 4. Thomas L. Halton et al. The effects of High Protein Diets on Thermogenesis, Satiety and Weight Loss: a Critical Review. Journal of American College of Nutrition, 2004.

Pharma & Healthcare News

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Pharmaceutical excipients present in your daily life BLANVER launches TABDONE® CL Crospovidone – a new effective super disintegrant agent for solid dosage forms

By Blanver TABDONE® CL Crospovidone is a super disintegrant agent widely used in solid pharmaceutical forms due to its high capillary activity and moisture content without gel formation.

The combination of TABDONE® CL‘s particular properties, chemical structure and particle morphology results in the benefit of a tablet’s rapid disintegration - independent of its size - by swelling without gel formation, thereby promoting accelerated dissolution without blocking or limiting the release of the APIs.

Because of its effectiveness at low levels, TABDONE® CL is ideally suited for use in formulations where there is not much room for a disintegrant.

Applications TABDONE® CL can be used in tablets manufactured by direct compression, wet and dry granulation.

TABDONE® CL characteristics • Promotes rapid disintegration in solid formulations; • High compressibility which is ideal in use with low compressibility APIs; • Presents an anionic character not forming complexes with ionic APIs.

Its porous and granular nature also facilitates low compressible APIs compression, resulting in tablets with higher hardness and less friability.

Recommended use levels Using 2-5% TABDONE® CL in solid formulations will improve the disintegration combining several mechanisms of action.

Regulatory Information CAS: 9003-39-8 For further information about TABDONE® CL, please contact Alsiano.

www.blanver.com

Article 410

Reduce the cadmium level of your finished products New cadmium limits in foodstuffs come into effect from 1 January 2015 The EU Commission has established revisions of cadmium limits in foodstuffs as set out in the Commission Regulation 488/2014 amending the Commission Regulation 1881/2006.

The maximum level of cadmium allowed will be as shown in the table.

Jost Chemical is specialised in producing mineral salts with very low content of metallic contaminants including cadmium. Although this update of the EC regulation still concerns maximum levels in the finished product, the choice of a Jost Chemical’s mineral salt is the guarantee to use an ultra-pure raw material which will pull downward the Cd level of your finished product.

Article 411

3.2

Cadmium

3.2.19

Infant formulae and follow-on formulae • powdered formulae manufactured from cows’ milk proteins or protein hydrolysates • liquid formulae manufactured from cows’ milk proteins or protein hydrolysates • powdered formulae manufactured from soya protein • liquid formulae manufactured from soya protein isolates, alone or in a mixture with cows’ milk proteins

Maximum level (mg/kg wet weight) 0.010 as from 1 Jan 2015 0.005 as from 1 Jan 2015 0.020 as from 1 Jan 2015 0.010 as from 1 Jan 2015

3.2.20

Processed cereal-based foods and baby foods for infants and young children

0.040 as from 1 Jan 2015

3.2.21

Food supplements excl. food supplements listed in point 3.2.22

1.0

3.2.22

Food supplements consisting exclusively or mainly of dried seaweed, products derived from seaweed, or of dried bivalve molluscs

3.0

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Drug delivery technologies for food, feed and pharmaceutical applications Develop new and innovative formulations with SEPPIC’s drug delivery system platform and overcome the challenges of fragile or bad tasting actives

By SEPPIC Pharmaceutical companies need to reformulate old active APIs in order to launch new galenic forms on the market. The purpose of this trend is to overcome competition from generic companies or file new patents.

API should be formulated in such a way that delivery into the body is changed compared to the old formulation.

With food and feed, the problem is somewhat different: All companies are willing to add nutrients or actives that have significantly decreased in, if not disappeared of, our modern alimentation into food supplements.

But these actives are often fragile (vitamins, antioxidants, etc.) or have a very bad taste (metallic salts) or do not withstand stomach conditions (low pH and presence of various enzymes).

To overcome these problems whilst allowing customers to develop new and innovative formulations, SEPPIC provides a drug delivery system platform using proprietary technologies developed with SEPPIC raw materials.

Technologies available for food and feed The following technologies are available to produce capsules that can be used to control delivery of actives whilst making bad taste or odour disappear if required.

Prilling The technology consists in melting a mixture of Seppic’s solid food or feed approved products, adding the active ingredient into the melt and making small liquid droplets, by means of vibrating nozzles or spinning disks.

When droplets fall into fresh air or liquid nitrogen, they become solid and are transformed into spherical solid microbeads containing the active ingredient.

Complex coacervation The technology consists in making a thin shell of 2 polymers (most often gelatin and arabic gum) around a water insoluble core. The core can be oil containing a lipophilic active ingredient or a solid drug. The main advantage of this technology is that the amount of active ingredient in the capsules can be as high as 70-80%. It (continues on page 10 >>)

SEPPIC drug delivery

technologies • Prilling

• Complex coacervation • Adsorption onto porous substrates • Ion exchange resins

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Pharma & Healthcare News

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The Alsiano Healthcare team Pharmaceuticals - cosmetics health & nutrition

Key accounts

Pharmaceuticals - cosmetics health & nutrition

Anders Hager

Lene Aarøe Nissen

Annette Strarup

M.Sc. Chem.

Sales director

B. Chem. Eng. 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: lan@alsiano.com Tel. dir.: +45 8230 0025 Mobile: +45 2270 1002

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

Pharmaceuticals - cosmetics health & nutrition

Quality

Process Technology

Hedvig Åkesson

Niels Kjær Nielsen

Susse Liff Hansen

M.Sc. Agriculture Area sales manager

Area sales manager

Quality manager

E-mail: haa@alsiano.com Tel. dir.: +45 8230 0009 Mobile: +46 708 155 012

E-mail: nkn@alsiano.com Tel. dir.: +45 8230 0072 Mobile: +45 2270 1017

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

Sales support

Sales support

Logistics

Malene Rask Harder

Signe Mørck

Lene Baldasano del Valle

Sales assistant

Sales assistant

Logistics manager

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

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

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

>> can be used for taste masking or for

preventing incompatibilities between several ingredients.

Adsorption onto porous substrates Liquid active ingredient is entrapped into the pores of a solid porous support. If sustained release or enteric capsules are required, additional coating of the obtained capsules is possible. This technology is mainly used to transform liquid into solid and to allow the incorporation of a liquid ingredient into tablets, capsules or sticks.

Additional technology for pharmacy Ion exchange resins Using porous ionic supports such as ion exchange resins allows creating ionic bonds between the support and the drug (if ionisable). These ionic bound bonds are disrupted in the presence of salts contained in the biological fluids (saliva, gastric juice, sweat, etc.). This property can be used to perform taste masking or sustained release.

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Cryogenic prilling pilot