PARTICLE COATING - TTC Technology Training Center

PARTICLE COATING:
NUTRACEUTICALS AND PROBIOTICS
Glatt TTC Workshop
Binzen, Germany
June 26-28, 2002
PREAMBLE
The industry workshop, the fifty-third in the Glatt series, attracted fifty participants,
predominantly from industry, including both users and producers of materials and technologies
for the food and life science industries. Attendees from Europe, the Americas, Africa, Asia and
Australia included academics and representatives from SMEs. The Workshop included
seventeen presentations related to markets, materials and technology, with a practical session
demonstrating granulation, hot melt coating, pellet coating and microcapsule production. The
workshop, which focused on food applications, was held in the Black Forest, just north of Basel.
The networking opportunities were interspersed with some excellent local cuisine as well as a
wine-tasting evening, particularly a variety of reds made from grapes harvested from vines which
are over one hundred years old.
GENERAL OVERVIEW
Gabrie Meesters (DSM, The Netherlands): Trends in the Food and Life Science
Industry There are two parallel trends, one in which consumers now spend less time cooking per
day, down to an average of 20 minutes, from 90 minutes fifty years ago. Given this, the
chemical industry sees an opportunity for higher margins in life and food sciences and is
transforming itself into a service provider. The food market is $2.8 trillion per year, with
another trillion not passing through supermarkets. Half of this market is the US and EU, with a
total of 25% of world food consumption on processed “food services”. Only 17% of food
consumption is in Asia, with the majority of “demand” in the raw ingredient category.
However, in the developing world there is a demand for prenatal and infant nutrition, given the
birthrate. The ingredient producers include Kerry Group, CSM, Roche, DSM, Rhodia, CP Kelco.
They sell to manufacturers such as Best Foods, Nestlé, Philip Morris, PepsiCo, Coca Cola, Mars
and Dannon. The top 10 ingredient and food manufacturers have 32% and 18% of the market.
The manufacturers sell to retailers, of which the largest is Walmart ($152B per annum), at times
passing through blenders. The food market also sees many synergies between businesses with
very different products designed to provide a fast or convenient service, including the gasoline
stations which now sell hot meals which can be purchased close to the home.
Meesters notes that there is an increasing demand for innovative ingredients. This
requires technologies which adapt to regional or national markets. Another important driver for
food development is the aging of the population. These demands require supply chain exchange
of information related to application know-how. Other tendencies include the concentration of
retails and the movement of food service providers into the retail market. Ingredient
manufacturers and food manufacturers are also merging, within their respective domains, with
the dietary supplement market expanding rapidly.
Food safety and hygiene is changing the structure of the food market, with meat
replacers increasing rapidly in sales. Issues for the consumers include the consumption of
hormones, genetically modified seeds as well as disease transmission. Food safety also impacts
on equipment (e.g. spray dryer) design and operation, with the need to consider the frequency of
cleaning as well as if wet or dry cleaning will be employed, both of which offer disadvantages.
Engineers must also consider that the selling price of coated enzymes, for example, is 100-1000
times lower than pharmaceuticals, though the demands for high quality, consistent, coated
materials, or pellets, remain constraints. This, therefore, requires combined technical solutions
including spray and fluidized bed drying with feed-foreword/feed-back control. Particle
specifications include density, strength, shape, moisture content and stability, both on average as
well as the distribution of these statistics within and between batches.
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PRODUCT DEVELOPMENT AND DESIGN
Tage Affertsholt (3A Business Consulting, Denmark): EU Health Claim Regulations
The EU defines a medicinal product as a substance or combination of substances
presented for treating or preventing disease in humans or animals, or restoring, correcting or
modifying physiological functions. Spurred by various national agencies related to food and
health, often regulated by different agencies, the EU is now discussing norms for labeling.
There are also proposals for directives on food supplements and fortified foods, both submitted
in mid 2000. Pan-European claims should come into force in mid 2004.
The EU commissioner for Health and Consumer Protection, David Byrne, recently stated
that the “prevention of a disease and (the) reduction of the risk factors of a disease are clearly
not the same, and we must be careful to avoid such confusion. Therefore, the development of
“biomarkers”, or indicators, which are both validated and predictive, as cholesterol and blood
pressure are for cardiovascular diseases. The use of these markers is expected to increase the
growth rate of functional foods and nutraceuticals, up to 10-20% per annum.
Claude Champagne (Agriculture Canada, Quebec): Challenges in the use of Coated
and Non-Coated Cultures in the Development of Foods Containing Probiotics
Probiotics are live microbial supplements, which beneficially affect the host by
improving the intestinal microbial balance. Benefits include facilitated digestion, a lower
incidence of diarrhea, lower cholesterol levels and incidents of colon cancer, as well as an
increase in the non-specific host resistance to pathogens. In the US, 60% of yogurts now
contain probiotic cultures.
Champagne reduced the development of functional foods into seven challenges:
1. Choice of strain
• In addition to cost and quality, religious influences are becoming increasingly more
important. Most strains are, for example, Kosher. Furthermore, the stability in dry and
frozen form is also an issue, as is stability in acidic conditions and compatibility with
other cultures and growth in milk. Oxygen tolerance for growth is almost always
important.
2. Concentration of the active ingredient
• There is a need for clinical data, along with an appreciation that there are significant
differences between people. Dosages vary from 10 6 to 10 9 CFU/mL.
1. Toxicity
• The issues of overdose, particularly in non-healthy individuals, are issues to resolve.
2. Incorporation into food
• The concentration after cold storage for long periods does not always correlate with the
initial level, implying that detailed studies are needed to select strains. Probiotics are also
quite sensitive to sugar level.
• To help the probiotics survive, in cheese for example, higher temperature coagulation of
cheddar and gouda has been advocated.
• Entrapment of culture in polysaccharides can significantly increase strain survival during
frozen storage. Cryoprotectants, such as mannitol and glycerol, within the bead, also
promote survival. Furthermore, beads of 30 micrometers or larger result in longer
probiotic survival.
3. Active component analysis
• Some strains are not easy to detect with typical analytical methods.
4. Storage stability
• Some fruits and extracts can kill the probiotic population.
• Lipid coating can improve stability.
5. Effect on sensory properties
• Examples of advantages include the reduction of undesirable side-flavors..
• Alginate beads can liberate some off-flavors.
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Denis Poncelet (ENITIAA, Nantes, France): Methods for the Encapsulation of
Nutraceuticals
Poncelet, the president of the Bioencapsulation Research Group, compared
immobilization methods for nutraceuticals. Spray-based methods include spray drying, jetcutting
and centrifugal extrusion. These compete with emulsion-based coacervation
technologies, film coating via fluidized beds or pan coating, and multi-lamellar vesicles. Film
coating, which remains relatively uncommon, has the advantage of permitting room temperature
processing. For large-scale applications, the static mixers are able to produce emulsions on the
order of seconds, versus minutes for emulsions agitated mechanically. These techniques, which
do not produce monodisperse spheres, can produce ton-sized quantities, as opposed to gram-tokilogram
levels for the balance of the methods.
David Hunkeler (AQUA+TECH, Switzerland): New Materials and Characterization
Methods
Encapsulation and coating materials differ in price by seven orders of magnitude, with
the value derived by the extent of purification as well as the retailing of batches proven for given
applications. Hunkeler’s second theme was the extreme sensitivity of microbead and
microcapsule properties to very minor changes in process conditions (e.g. reaction time, buffer
concentrations). Microcapsule mechanical properties were also shown to correlate with
membrane volume, with permeability decoupled via the use of coatings. Therefore, the control of
capsule quality (e.g. size and permeability distributions within and between batches) by advances
in downstream processing and the application of oligocations is an important in moving toward
reproducible up-scaled sterile systems. Overall, Hunkeler predicted a market opportunity for the
retailing of marine polysaccharides with specific properties (e.g. endotoxin and protein levels,
microstructure, viscosity) and guaranteed application efficacy. The later would include batches
tested and proven for applications in food, pharma/biotech and clinical transplantation.
EXCIPIENTS
Jörg Brunemann (Syntapharm, Germany): The Most Popular Excipients for Spray
Coating Film coating with carbohydrates, lipids, proteins, terpenes (e.g. shellac) and pigments
was reviewed. Typically, spray coating on nutraceuticals utilizes cellulose ethers which have the
advantage of solubility in cold water. However, the film elasticity, at least in the case of methyl
cellulose, requires the addition of a plasticizer such as stearic acid. Interestingly, elasticity tends
to correlate with stickiness.
“Biogums” such as Gum Arabic are very low viscosity polysaccharides which render it
suitable as a coating agent. The biogums, including xanthan, Guar gum and Locust Bean gum
all dissolve, or disperse, well in cold water and are good thickeners, where they function better
than as coating agents. Lipids are used for moisture protection and are sprayable at
temperatures as low as 30 o C. In contrast, waxes, such as Carnauba, have a polishing effect and
a higher melting point. Shellac, provides very dense films and is excellent for taste and odor
masking as well as humidity protection. Shellac’s main disadvantage is a loss of solubility of
the coating with storage if sprayed with alcohol, though it is now available in aqueous solutions,
solubilized with ammonium carbonate.
Ian Marison (Swiss Federal Institute of Technology): Excipients for Liquid
Encapsulation
“Liquid Core” capsules have been applied in medical, pharmaceutical, food and
bioconversion applications. Excipients include polyelectrolytes of natural and synthetic origin,
crosslinked polymers as well as those gelling thermally (e.g. collagen) or photopolymerizing.
An innovative modification to the standard microcapsule chemistry involved the treatment of
alginate-poly-L-lysine capsules with sodium hydroxide. The resulting dense membrane had
improved durability. Marison, in association with Inotech, encapsulated yeast cells and showed
that the solvent does not influence the cells, with the capsules stable in the fermenter. He also
revealed that autoclaved capsules are smaller and much weaker than the non-purified parents.
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Frank Runge (BASF Fine Chemicals, Germany): Formulation of Nutraceuticals for the
Food and Supplement Industry
Micronutrients as food supplements include vitamins, both water- and fat-soluble,
Carotenoids as well as nutraceuticals, such as Omega-3 fatty acids and lycopene. BASF is
preparing oil-in-water emulsions containing 1-micrometer droplets as a means of encapsulation.
Spray agglomeration is preferred to spray drying or spray-formulation/cooling, though the latter
results in solid “beadlets” of 200 micrometers in diameter. Spray-formulation is carried out at
lower temperatures (less than 70 o C) which are misted through the top of a fluidized bed tower
and coated with a fine powder matrix. The stabilizer, typically gelatin, acts as a matrix and
supports the micronutrients. It is subsequently coated in a starch or silica outer layer. The
resulting core-shell beadlets are quite mechanically stable, even to tablet compression, also
providing a good oxygen barrier. They can also have micronutrient loadings on the order of 25-
75%. The BASF system is essentially the opposite of the Glatt coating, where an emulsion is
coated onto a powder.
Carotenoid nanoparticles are produced by milling, precipitation, intense emulsification or
mixed micelle systems. The former two lead to solids. The precipitation process requires a
dissolution of the Carotenoid in hot alcohol (200 o C) at high pressures (50 bars). This is mixed,
rigorously, with a protective colloid, in a continuous process resulting in a precipitation
generating a core of Carotenoid with a colloidal shell.
For beverage applications, colloid stability is the key and the adsorption of emulsifiers,
polymers or polyelectrolytes are common. The natural polyions, such as Gum Arabic or
modified starch, provide the best stability, provided the high molar mass polymers are properly
hydrated.
Friedrich Heinze (National Starch/ICI, Germany): Functional Nutraceutical
Carbohydrates
At least 55%, and as much as 75%, of human energy need is derived from
carbohydrates. The ideal nutritional scenario requires a variety of starches with different
degradation rates in the small intestines and colon. The “resistant” starch intake has been
shown to correlate well with lower incidence of colon cancer. However, EU consumption is
currently at 4 grams per day, tenfold lower then is recommended, though vegetarians eat over 20
g per day. Resistant starches come from unmilled whole grains, fruits, vegetables, green bananas
as well as cooked potatoes. In addition to food supplement, resistant starch is envisioned for
satiety and obesity control.
Glycemic carbohydrates focus on the small intestine. They are used, for example, to increase the
availability of carbohydrates and reduce the peak of the gycemic response following eating.
They are also advocated as sports foods, reducing the pasta intake prior to very strenuous
activities.
PROCESS TECHNOLOGY
Caroline Mähr (Technology Transfer Center, Bremerhaven, Germany): Encapsulation
in Food Technology
The German food industry is characterized by SMEs with only 2.4% of the 6000 firms
having more than 500 employees. The Food industry, the fourth largest German economic
sector, has a growth of 1% per annum, despite quite extensive new product introduction. This is
due, in part, to a reduction of disposable income allocated to nutrition, down from 22% in 1990
to 15% a decade later. The Technology Transfer Center (TTZ) in Bremerhaven is a non-profit
center geared to assisting these SMEs with product innovation. It has five institutes, one of
which, BILB, is dedicated to food process and product development, including encapsulation.
TTZ functions based on queries from firms, providing accelerated product or process
development via an outsourced research development. They also identify partners, write
proposals, and carry out the scientific and administrative co-ordination. At present TTZ
participates in fifty European grants. Bremerhaven has also launched a Biocenter for food and
biotech startups.
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Sebastian Pfûtze (Glatt, Germany): Continuous Fluid Bed Coating
Spray granulation is a process where there is a solid incipient used as a starter onlyd,
though their is a larger fraction of powders produced from the liquid itself. It can be contrasted
with coating technology where the incipient always serves as a core. Spray granulation is
preferred for sizes below above 200 micrometers. Typically, the viscosity at the particle has to
be low for good spreading and an even coating. This implies a low solid concentration in the
spray liquid. The final particles are sieved, with the smaller fractions recycled back to the inlet of
the continuous bed. The oversized particles are milled, with, again the smaller fraction fed back.
Importantly, all particles grow at the same rate, implying no change in the breadth of the particle
size distribution with time.
Pfûtze noted that agglomeration is lower for bottom (Wurster) spray fluidized beds than
for top spray based systems. He also mentioned that there is very similar coating properties in
batch and continuous fluidized beds. However, for the latter, the ratio of the mean mixing and
residence times are important influences on the breadth of the particle size distribution.
As an example of the productivity of the continuous beds, a 7.5 m 2 bottom bed area can
produce 5 Tons per hour of product.
Klaus Eichler (Glatt, Germany): Technological and Qualitative Evaluation of Bottom,
Top and Tangential Spray Coating
Eichler compared the advantages and disadvantages of the various spraying techniques.
Key parameters include the spreadability of the droplet on the substrate as well as the ratio of the
droplet to substrate size (must be much less than unity). The spreadability is extremely sensitive
to the bed temperature.
Top spray is a counter-current process, which results in an inhomogeneous coating. It is
useful as a barrier coating, though perhaps not for taste masking. Top spray has the advantage
of having the shortest processing times. Bottom spray prevents these handicaps by reducing the
distance between the spray tip to the surface. This permits smaller spray droplets, whose size is
governed by the air volume through the nozzle’s orifice. Wurster is the most reliable process,
batch to batch, as well as having a very uniform droplet size distribution. The Wurster also has
the advantage of being able to uniformly coat non-spherical, and highly irregular, particles.
Tangential coating (rotating discs) are basically horizontal Wurster’s with essentially
identical coating properties. This technology is usually used to add high quantities of coating
material, up to 300-800% per hour. Its a dry powder coating which basically accumulates in a
snowball effect by rolling up on the disk. However, it is less versatile than the Wurster and has
a high risk for agglomeration.
Muriel Jacquot (ENSIA, Nancy, France): Spray Coating of Enzymes
Lactoperoxidase, thiocyanate and hydrogen peroxide, is a natural “LPS” system present
in raw milk and is, therefore, advocated as an alternative to chemical preservatives for transport to
the dairy. Jacquot is using LPS, in microbeads, to protect the surface of foods, such as fish.
The bead includes a core of acacia gum with glucose, loaded with thiocyanate and spray dried.
Enzymatic coatings are added via fluidized bed with bottom spray. This reduces the risk of
allergy during handling of powders and the health risks associated with dusts. The encapsulated
system had very good flow- and handle-abilities and showed less than 25% losses in activity
over ten months, rendering it a low cost industrial alternative.
David Hunkeler
AQUA+TECH Specialties S.A.
Route de St. Eloi, CH-1350 Orbe
Switzerland
david.hunkeler@aquaplustech.ch
Klaus Eichler
Glatt TTC
Binzen, Germany
klaus.eichler@glatt.de
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