Title of Invention

"STABLE COATED MICROCAPSULES"

Abstract THE PRESENT INVENTION PROVIDES A PROCESS FIOR THE PREPARTION OF A MICROENCAPSULATED COMPOSITION CONTAINING LIPOPHILIC COMPOUNDS COMPRISING OF THER FOLLOWING STEPS (1) PARTICEL SIE REDUTION OF THE LIPOPHILIC CIMPOUND IN THE PRESEBN E OF A SURFACE ACTIVE AGENT;(11) PPRE4PARINMG A SOOLUTION OF ALKLI METAL ALGINATER ;(III) COMBINING THE SOLUITIOONS OF STEP (1) AND STEP (11). (IV) ADDING DROPWISE THJE SOLUTION OBTAINED FROM STAGE (III) TO A SOLUTION OBTAINED FROM STAGWE (III) TO A SOLUION CONTAINING CA2+ OBTAING BEADLETS, AND REMOVING THE FORMEDE BEADLETS FROM SAID SOLUTION ;(V) RINMSING THJE BEADLETS WI9TH AND ACIDIC SOLUTION AND DRYING ;(VI) COATING THE BEADLETS OBTAINED FROM STEP (V) TO OBTAIN THE MICROCAPSULES. THE PRESET INMVENTION, INM ONE ASPECT, RELATES TO A MICROENCPSULATED COMPOSITION OCMPRISING OF ONE OR MORE LIPOPHILIC OMPOUND ENVFELOPED BY A SURFACTANT WHICH IS ENCAPSULATED IN AN LAGINATE MATRIX AND FURTHER COATED WITH AN OUTER COATING, WHERIN TH4 PARTICLE SIZE OF THE LIPOHILIC SUBSTRANCE IS NOT GREATER THAN 20 AM;.
Full Text STABLE COATED MICROCAPSULES
FIELD OF THE INVENTION
The present invention relates to microencapsulated compositions of lipophilic
compounds, having improved stability and to a method for preparing said composition.
BACKGROUND OF THE INVENTION
Processes for encapsulating oils and oil soluble substances are well known in the art.
US 4,389,419, for example, which is incorporated herein by reference, relates to a
process for encapsulating oils and oil-soluble substances in multi-compartmentalized,
mechanically stable microcapsules. The process comprises the steps of first forming an
emulsion consisting of a continuous phase comprising an aqueous solution of an alkali
metal alginate and optionally a water-soluble, alcohol-insoluble filler such as a
polysaccharide, and a dispersed phase of an oleophilic substance such as one or more
vitamins dissolved in an oil. The emulsion is then formed into droplets which are
thereafter immersed in an alcoholic solution of multivalent cations, to produce a shape-
retaining alginate matrix filled with precipitated polysaccharide and enclosing plural oil
droplets. The vitamins are thereby protected from oxidative degradation and can be
handled like conventional crystalline solids.
Algin is a polysaccharide found in brown algae. Alginates and their derivatives have
become significantly important hydrocolloids and are applied in a wide variety of
industrial fields.
Algin is a polysaccharide that contains ß-(l ?4)-D-mannuroic acid of structure I:
and a-(1?4)-L-guluronic acid of the structure II:
Algin is a heterogeneous polymer consisting of the following three types of molecular
blocks:
a) M-block, consisting of only M-M linking;
b) G-block, consisting of only G-G linking; and
c) Random block, M and G randomly linked.
Calcium alginate gel beads are used to entrap a wide variety of substances. The
entrapment with calcium alginate is particularly favored because of the mild conditions
employed and the nontoxicity of the reactants. Typically, the procedure simply involves
dropping a 1-2% solution of sodium alginate into a 1-2% solution of calcium chloride.
The alginate solution may be pumped through a small orifice, such as a needle, or
rotating plate or vibrating droplets feeder and allowed to free-fall, producing a spherical
bead, which gels upon contact with the calcium source. The beads then remain in the
calcium bath until hardened.
Islets of Langerhans, the cells producing the insulin in the pancreas, may be entrapped
in an alginate polycation microcapsule to allow small molecules such as glucose and
other nutrients to diffuse freely, while preventing the passage of large molecules and
cells. Physico-chemical properties of the microcapsules, such as shape, size and
permeability, can be controlled (Goosen et al., Applied Biotechnology and
Bioengineering, 10, 87-98, 1984).
According to US 4,389,419, "...the amount of oil used may range broadly between 1%
and close to 30%. However, at the higher end of the range, the stability of the oil-in-
water emulsion is decreased, and the quality of the microcapsule is reduced." (column 3
lines 5-9).
BASF Health and Nutrition publication dated 10.97 reports a process for
microencapsulation using gelatin. In this report, the mean particle size of the final
product is approx. 250µ and the concentration of the active ingredient is up to 50%.
However, the BASF process involves the use of gelatin, which is an undesirable
limitation. Gelatin is purified mainly from pigs and cows which are susceptible to The
Mad Cow disease and the Foot and Mouth disease.
U.S. 6,146,671 discloses a method for protecting a heat and/or oxygen-labile compound
by encapsulation in a protective matrix of alginate and an additional polymeric material,
which provides a single layer coating system. U.S. 6,146,671 farther suggests the use of
gelatin as a preferred protective polymer. Recently, the market is looking for materials
which are not derived from animals which are susceptible to Mad Cow Disease.
In view of the above, the need for a stable, GMO-free, vegetable source alginate
microcapsule having a high lipophilic compound content, small particle size with
improved bioavailability, remains.
It is therefore the objective of the present invention to provide a microencapsulated
formulation of lipophilic compounds which contains a relatively high Iipophilic
compound content with improved bioavailability and stability.
SUMMARY OF THE INVENTION
The present invention provides a process for the preparation of a composition containing at
least one microencapsulated lipophilic compound comprising:
(i) particle size reduction of the lipophilic, compound in the presence of (1) a surface active
agent and (2) water or a water miscible solvent or a mixture thereof, to provide a first
composition comprising an emulsion or suspension of surface active coated lipophilic
particle in said water or water miscible solvent or mixture thereof;
(ii) providing a solution of alkali metal alginate;
(ui)combining said first composition and the alkali metal alginate solution to provide a
second composition;
(iv) adding dropwise the second composition to a solution containing Ca2+, thereby obtaining
beadlets having a second coating of Calcium alginate, and removing the formed beadlets
from said solution;
(v) rinsing the beadlets with an 0.1% to 10% acidic solution and dying said beadlets to obtain
dried beadlets; and
(vi) coating the dried beadlets with a third coating material to obtain microcapsules
containing said lipophilic compound, said coating material being of vegetable origin and
being selected from the group consisting of cellurose derivatives, waxes, fats, proteins
and polysaccharides.
compounds is not greater than 20 µm, and rinsing the alginate beadlets with an aqueous
acidic solution before the final drying of the beadlets, provides a microcapsule wherein
the lipophilic compound displays improved bioavailability.
The lipophilic compounds suitable for the present invention are lipophilic compounds
which are sensitive to heat or oxygenating conditions. Non-limiting examples of
lipophilic compounds are carotenoids (e.g., lycopene, beta and alpha-carotene, lutem,
astaxanthin, zeaxanthin), vitamin A, vitamin E, vitamin D, omega 3, omega 6 oils and
mixtures thereof. Further lipophilic compounds suitable for the present invention are
lipophilic compounds which have a taste or smell which is required to be masked, e.g.,
bitter tasting vitamins and fish oil. Throughout the description the term lipophilic
compounds encompasses the foregoing definition and mixtures of said compounds.
According to a particular embodiment of the process of the present invention, a solution
containing 0.01% to 5% of a surfactant agent, 0.1% to 5% of a lipophilic compound,
wherein said lipophilic compounds are selected from among a group comprising of
lycopene, beta-carotene, lutein ,alfa-carotene, astaxanthin, zeaxanthin, vitamin A,
vitamin E, vitamin D, omega 3 and omega 6 oils, or mixtures thereof, and 0% to 20% of
a filler is prepared. Said solution is processed for size reduction of the particles of the
lipophilic compounds. Wherein the lipophilic compound is in solid form said solution is
processed in a grinder and wherein the lipophilic compound is in liquid form said
solution is processed in a high shear mixer. The processing of the lipophilic compound
with a surface active agent (surfactant) creates a coating of the surfactant around the
particles of the lipophilic compound, i.e. a primary protective layer. Following size
reduction, a separate alkali metal alginate solution is prepared by dissolving an alkali
metal alginate in water to provide a solution containing 0.5% to 10% of an alkali metal
alginate, preferably 1.5% sodium alginate in water. The alkali metal alginate solution is
mixed with the solution containing the lipophilic compound. The resulting solution is
homogenized to provide a substantially homogenous emulsion or dispersion which is
added drop-wise to a solution containing 0.2% to 5% of Ca2+, preferably 1.5% calcium
chloride. The drop-wise addition is carried out such that the drops are not bigger than
1000 µm. Thus, upon contact of the drops with the Ca2+ solution, beadlets of lipophilic-
compound-containing alginate is formed. This creates a second protective layer for the
lipophilic compound. The size of the beadlets can be controlled by controlling the size
of the droplets. Preferably the size of the drops is adjusted so as to provide beadlets in
the size range of about 100 µm to 450 urn. The beadlets are than separated from the
solution by conventional separating means, e.g., screening, and rinsed with an aqueous
acidic solution. The acidic solution is preferably a 0.1% to 10% solution of an acid
selected from among a group comprising of citric, aspartic, acetic, ascorbic, lactic,
phosphoric or hydrochloric acid. More preferably, said acidic solution is a 2.5%
solution of citric acid or phosphoric acid in water. The rinsing with an acidic solution
effects shrinkage of the beadlets and improves the bioavailability of the
microencapsulated lipophilic compound. The beadlets are then dried according to
drying methods known in the art, preferably, by fluidized bed drying. "Drying" meaning
lowering the water content below 10%. The dry beadlets are then coated with a coating
material in a fluidized bed apparatus, according to the coating technique described in
U.S. Patent No. 4,710,384, incorporated herein by reference. Hence, a third coating
layer is provided. Suitable coating materials for the final coating stage are cellulose
derivatives, waxes, fats, proteins or polysaccharides. Non-limiting examples of cellulose
derivatives suitable for coating material are: ethyl cellulose, hydroxy propyl cellulose,
hydroxy propyl methyl cellulose and methyl cellulose. Waxes can be carnauba wax,
candelila wax and beeswax. Fats can be hydrogenated vegetable oils, e.g. soybean and
palm oil, mono and diglycerides, stearic, palmitic acids. Proteins can be albumins, zein,
soy proteins or milk proteins. Polysaccharides can be starches, maltodextrins, pectins,
xanthan gum, gum Arabic or carrageenan. According to a particular embodiment of the
present invention, wherein there is no restriction regarding the use of products derived
from animals, gelatin may be applied as a suitable protein for the third layer coating.
The operation of size reduction in stage (i) of the present invention may be effected in a
liquid medium. The liquid medium may be water or other water miscible solvents
wherein non-limitive examples of suitable liquids are alcohols e.g., methanol, ethanol,
iso-propanol, acetone and ethyl acetate. Accordingly, the liquid is added to the solution
of stage (i) which contains the lipophilic compound and surface active agent.
According to yet a further embodiment of the present invention, the drying and final
coating are carried out in one step in a fluidized bed apparatus.
According to a particular embodiment of the present invention when the lipophilic
compound is in liquid form, stage (i) of the process is carried out so that the drop size of
the lipophilic compound is reduced to a size not greater than 20 µm, preferably in the
range of 3 µm to 7 µm, and the solution obtained from stage (i) is an emulsion or
suspension.
In yet a further preferred embodiment of the present invention the lipophilic compound
is selected from among a group consisting of beta-carotene, lycopene, alpha-carotene,
lutein, astaxanthin, zeaxanthin, vitamin A, vitamin E, vitamin D, omega 3 and omega 6
oils, wherein the microcapsule contains 0.1% to 40% of said lipophilic compound or
mixtures thereof.
Suitable fillers for use in stage (i) and/or (ii) of the process are selected from among a
group comprising of polysaccharides e.g., pectin, starch, carrageenan, gum Arabic,
xanthan gum, carboxymethyl cellulose, methyl cellulose, hydroxypropyl cellulose,
proteins from soybean, corn, milk or whey.
The term "surfactant agent" refers to any substance which has emulsifying, colloidal,
stabilizing or dispersing qualities. Non-limiting examples of suitable surfactants can be
non-ionic, anionic or cationic surfactants, e.g., alcohol alkoxylates; alcohol ethoxylates;
alkylphenol alkoxylates; alkylphenol ethoxylates; alkyl polysaccharides; block
copolymers e.g., ethoxylated polypropylene oxides, alcoxylated ethylene diamine; esters
e.g., glycerol mono and distearate, glycerol mono and dioleate; ethoxylated sorbitan
esters and sorbitan esters, different proteins e.g. protein from soybean, corn or whey.
According to a particular embodiment of the present composition, the
microencapsulated lipophilic-cornpound-containing composition contains 0.1% to 40%
of a lipophilic compound selected from among beta-carotene, lycopene, alpha-carotene,
lutein, astaxanthin, zeaxanthin, vitamin A, vitamin E, vitamin D, omega 3 and omega 6
oils or mixtures thereof, wherein the particle size of the lipophilic compound is not
greater than 10 µm, preferably between 2 µm and 5 µm. Said composition further
comprises a surfactant, an alginate matrix which incorporates the surfactant-coated
lipophilic compound and a coating which coats the lipophilic-compound-containing
alginate matrix. The coating material is selected from among a group comprising of
cellulose derivatives, waxes, fats, proteins and polysaccharides.
The microencapsulated compositions according to the present invention are suitable for
tablet preparation, hard shell capsule filling and incorporating in different foods.
According to a particular embodiment of the present invention, the lipophilic
compounds or mixtures thereof employed herein may further comprise fillers,
excipients or additives. Examples of suitable fillers are starch, pectins, carraginanes,
xanthan gums, proteins, polyethylene glycols, cellulose derivatives (e.g., methyl
cellulose, hydroxypropyl cellulose and ethyl cellulose) and other polysaccharides.
The microcapsule prepared according to the present invention comprises of three
protective layers which protect the lipophilic compounds. The first protective layer is
created by the surfactant; the second protective layer is created by the alginate matrix
and the third layer is the final coating layer.
According to a further aspect of the present invention The present process is suitable for
encapsulating lipophilic compounds which have a taste or smell which is required to be
masked. This is particularly important for introducing lipophilic compounds into food
stuff and beverages wherein said lipophilic compound has a taste or smell which is
offensive to the consumer or does not correlate with the taste or smell of the food stuff
and beverage. For example masking the taste of a bitter tasting lipophilic compound
wherein said lipophilic is added to a sweet or salty food. This effect is achieved by the
present process without inhibiting the bioavailability of the lipophilic compound.
The present invention is advantageous in that it provides microcapsules of lipophilic
compounds with improved stability, relatively high content of the lipophilic compound
and improved bioavailability of the lipophilic compound. These advantages are
achieved by the process which provides a three layer coating of the lipophilic compound
and by the small particle size of said compounds. The advantages of the present
composition are also found it the improved mechanical properties of the microcapsules
which is achieved by the third layer coating. Thus, the microcapsules of the present
invention are also tablet grade, i.e. suitable for use in tableting. Furthermore the
compositions of the present invention are gelatin free. Due to the fact that the common
use of gelatin is obviated according to the present invention, the product of the present
invention is from vegetable origin.
EXAMPLES
Example 1
Encapsulation of Beta-Carotene by the present invention was done as follows:
In the first step the following ingredients were taken:
(a)
1. Natural beta-Carotene crystals (DSM ) - 36.6g.
2. Decaglyceryl monooleate - 17.4g.
3. Sucrose palmitate - 17.4g.
4. Water - 580.0g.
All ingredients were mixed and grinded together to form a homogenous suspension with
particle size less than 5 microns.
In the second step the following ingredients were dissolved:
(b)
1. Sodium Alginate - 180.0 gr.
2. Starch (from Peas) - 120.0 gr.
3. Water - 11420.0 gr.
The two solution were mixed together to form a homogenous suspension. The
suspension was fed through a dispenser, installed above a 1.5% Calcium chloride
solution in water. The spherical droplets, upon entering the solution, gel to form Beta-
Carotene alginate matrix beads when retained in the solution for 5 to 30 minutes. The
beadlets were collected by filtration and washed in 2.5% citric acid in water. The
beadlets were dried and then coated in a fluidized bed dryer and coater. The coating
material was made from the following ingredients:
(c)
1. Hydroxypropylcellulose - 70.0g.
2. Methanol - 177.0g.
3. Acetone - " 369.0g.
This process yielded coated dry spherical beads containing encapsulated ß-Carotene.
The particle size of 85% of the beads was between 150 microns and 425 microns.
Example 2
The process of Example 1 is repeated with a different composition of solution (b):
1. Sodium Alginate - 180.0 g.
2. Pectin (high ester) - 120.0g.
3. Water - 11420.0g.
Example 3
Encapsulation of Lycopene was performed as follows:
The following material were ground and homogenized together at 40°C until the particle
size of the lycopene was in the range of 2-5 urn:
(a)
1. Natural tomato oleoresin (20% Lycopene, Lycored)* - 139.0g.
2. Ethanol - 150.0g.
3. Decaglyceryl monooleate - 22.7g.
*Particle size of lycopene 50-110 µm
A second solution was made at 70°C:
(b)
1. Sodium Alginate - 180.0g
2. Sucrose palmitate - 22.7g.
3. Starch (from Peas) - 120g
4. Water - 12000.0 g
Solution (a) was added to solution (b) and mixed to form a homogenous suspension.
The dropping and coating processes are repeated, as in Example 1, with the coating
solution containing:
(c)
1. Hydroxypropylcellulose - 95.9gr.
2. Methanol - 242.0gr.
3. Acetone - 506.0 gr.
This preparation yielded coated dry spherical beadlets encapsulating lycopene with
particle size of 70% of the beadlets between 150 and 400 microns.
Example 4
Encapsulation of DHA (Docosahexaenoic acid) oil was performed in the following way:
The following ingredients were homogenized together in a high sheer mixer to provide
a fine emulsion:
(a)
1. DHA oil from algae (40% DHA) - 220g.
2. Sorbitan monolaurate - 8.0g.
3. Water - 1000.0g
A second solution was prepared from the following materials:
(b)
1. Sodium alginate - 75.0g.
2. Starch (from Peas) - 150.0g.
3. Water - 9000g.
The two solutions were mixed together to form a homogenous suspension. The
dropping filtering, washing, drying and coating was performed as in Example 1. The
coating solution was made from the following ingredients:
(c)
1. Hydroxypropyl cellulose - 85.0g.
2. Methanol - 215g.
3. Acetone - 447.0g.
The process produced coated dry spherical beads of encapsulated DHA.
Example 5 - Improved Bioavailability and Stability - Comparative Test
The microcapsules prepared by the present invention were tested for stability
and bioavailability. Stability tests were done by incubating the microcapsules in pure
oxygen atmosphere for 10 to 40 days at room temperature (25°C) and then assay the
microcapsules for their lipophilic compound content. Bioavailability was checked using
a USP type 2 dissolution apparatus. The microcapsules were incubated in gastric fluid
(0.1M HCl) for one hour at 37°C with the paddles rotating at 75RPM. Then the pH was
raised to 7 with the addition of tri-sodium phosphate 0.2M solution. In addition, cholic
acid 0.1% and SDS (sodium dodecyl sulfate) 0.1% were added to simulate an intestinal
fluid. After another three hours the solution was sampled and filtered. The filtrate was
assayed for the concentration of the lipophilic compound. The bioavailability was
estimated by the percent of the lipophilic compound from the microcapsules that was
dissolved in the simulated intestinal fluid.
Microcapsules prepared according to Example 1 were examined for
bioavailability which was found to be 86%. A similar preparation in which the beta-
carotene was not ground in the presence of the surfactant the bioavailability was 4%.
This shows the importance of the first layer of coating and the particle size of the
lipophilic compound in the bioavailability of the lipophilic compound.
When the microcapsules that were made as in Example 3 were tested for
stability the lycopene content of the microcapsules was reduced in ten days in oxygen
atmosphere by 7%. Similar microcapsules that were not washed in acidic solution but
prepared similarly otherwise their Lycopene content was lowered by 25% in ten days in
oxygen atmosphere. This shows the importance of the acidic wash for the stability and
bioavailability of the lipophilic compound.
Example 6: Tableting of the microcapsules
The suitability of the beadlets for tableting, i.e. tablet grade was evaluated by tablet
compression in a Korsch EKII single punch tablet press. The beadlets (30g) were mixed
with 190g of microcrystalline cellulose, 2.25g of magnesium stearate and 2.25g of
sodium starch glycolate. The mixture was compressed in the tablet press using a 12mm
die producing tablets of 680mg in weight with strength of 12kg. Using beadlets
produced in Example 1 and 3 gave tablets spotted with dark red spots. When these
tablets were put in oxygen atmosphere, as mentioned above, no reduction in the
concentration of beta-carotene (Example 1) or Lycopene (Example 3) was observed
after 10 days. In comparison, beadlets that were not coated with hydroxypropyl
cellulose were produced. These beadlets were identical to those made in Example 1 and
3 but were not coated with solutions (c) in each example. When these beadlets were
compressed into tablets with the same composition, the tablets were stained orange
indicating that the beta-carotene and the Lycopene were leaking out of the uncoated
beadlets. In addition, these tablets show reduction in beta-carotene concentration (-30%)
and in Lycopene concentration (-36%) in 10 days in oxygen atmosphere. This shows the
importance of the third coating layer for the stability of the microencapsulated lipophilic
compound and for its suitability to tablet compression.
While embodiments of the invention have been described by way of description, it will
be apparent that the invention may be carried out with many modifications, variations
and adaptations, without departing from its spirit or exceeding the scope of the claims.
It should be understood that some modification, alteration and substitution is anticipated
and expected from those skilled in the art without departing from the teachings of the
invention. Accordingly, it is appropriate that the following claims be construed broadly
and in a manner consistent with the scope and spirit of the invention
We Claim:
1. A process for the preparation of a composition containing at least one
microencapsulated lipophilic compound comprising:
(i) particle size reduction of the lipophilic, compound in the presence of (1) a surface
active agent and (2) water or a water miscible solvent or a mixture thereof, to
provide a first composition comprising an emulsion or suspension of surface
active coated lipophilic particle in said water or water miscible solvent or mixture
thereof;
(ii) providing a solution of alkali metal alginate;
(iii)combining said first composition and the alkali metal alginate solution to provide
a second composition;
(iv) adding dropwise the second composition to a solution containing Ca2+, thereby
obtaining beadlets having a second coating of Calcium alginate, and removing the
formed beadlets from said solution;
(v) rinsing the beadlets with an 0.1% to 10% acidic solution and dying said beadlets
to obtain dried beadlets; and
(vi) coating the dried beadlets with a third coating material to obtain microcapsules
containing said lipophilic compound, said coating material being of vegetable
origin and being selected from the group consisting of cellurose derivatives,
waxes, fats, proteins and polysaccharides.
2. A process as claimed in claim 1, wherein the particle size of the lipophilic
compound is reduced to a particle size not greater than 20 µm.
3. A process as claimed in claim 2 wherein the particle size of the lipophilic
compound is reduced to a particle size not greater than 10 µm.
4. A process as claimed in claim 1, wherein the alkali metal alginate is sodium or
potassium alginate.
5. A process as claimed in claim 1 wherein a filler is added to stage (i).
6. A process as claimed in claim 1, wherein the lipophilic compound is selected
from the group consisting of lycopene, beta and alpha-carotene, lutein,
astaxanthin, zeaxanthin, vitamin A, vitamin E, vitamin D, omega 3 oils, omega 6
oils and mixtures thereof.
7. A process as claimed in claim 1 wherein a filler is added to stage (ii).
8. A process as claimed in claim 1, wherein the lipophilic compound containing
alginate beadlets are in the size range of 100 to 425 µm.
9. A process as claimed in claim 1 wherein the acidic solution is an acidic aqueous
solution of an acid selected from the group consisting of citric, aspartic, acetic,
ascorbic, lactic, phosphoric and hydrochloric acids.
10. A process as claimed in claim 1, wherein the third coating is said cellulose
derivative comprising hydroxypropylcellulose.
11. A microencapsulated composition comprising of one or more lipophilic
compounds enveloped by a surfactant agent, encapsulated in an alginate matrix
providing beadlets of size about 100 µm to 450 urn, and further coated with an
outer coating of vegetable origin, wherein the particle size of the lipophilic
substance is not greater than 20 urn, said composition being made by the process
as claimed in claim 1.
12. A composition as claimed in claim 11 wherein the lipophilic compound is
selected from the group consisting of lycopene, beta and alpha-carotene, lutein,
astaxanthin, zeaxanthin, vitamin A, vitamin E, vitamin D, omega 3 oils, omega 6
oils and mixtures thereof.
13. A composition as claimed in 11 wherein the particle size of the lipophilic
compound is not greater than 10 µm.
14. A composition as claimed in 13 wherein the particle size not greater than 5 µM.
15. A composition as claimed in claim 15 wherein the size of the microcapsules is in
the range of 50 µm to 950 µm.
16. A composition as claimed in claim 15 wherein the size of the microcapsules is in
the range of 100 µM to 450 µm.
17. A composition as claimed in claim 11 comprising 0.1% to 40% of a lipophilic
compound or mixtures thereof.
18. A composition as claimed in claim 11 wherein the outer coating is a material
selected from the group consisting of cellulose derivatives, waxes, fats, proteins
and polysaccharides.
19. A composition as claimed in claim 17 wherein the outer coating is
hydroxypropylcellulose.
20. A composition as claimed in claim 11 wherein said composition is tablet grade.
21.A method for incorporating lipophilic compounds in food stuff comprising of
encapsulating the lipophilic compound according to the process as claimed in
claim 1 and adding the encapsulated composition to food stuff.
22. A method for masking the flavor and/or smell of lipophilic compounds comprising
encapsulating the lipophilic compound according to the process as claimed in
claim 1.
The present invention provides a process for the preparation ofa microencapsulated composition containing lipophilic
compounds comprising of the following steps:(i) Particle size reduction of the lipophilic compound in the presence of a surface active
agent;(ii) Preparing a solution of alkali metal alginate.(iii) Combining the solutions of step (i)and step (ii).(iv) Adding dropwise the
solution obtained from stage (iii) to a solution containing Ca2+, obtaining bead lets, and removing the formed beadlets from said
solulion;(v) Rinsing the beadlets with an acidic solution and drying;(vi) Coating the beadlets obtained from step (v) to obtain the
/microcapsules.The present invention, in one aspect, relates to a microencapsulated composition comprising of one or more lipophilic
compound enveloped by a surfactant which is encapsulated in an alginate matrix and further coated with an outer coating, wherein
the particle size of the lipophilic substance is not greater than 20m.

Documents:

201-kolnp-2004-granted-abstract.pdf

201-kolnp-2004-granted-assignment.pdf

201-kolnp-2004-granted-claims.pdf

201-kolnp-2004-granted-correspondence.pdf

201-kolnp-2004-granted-description (complete).pdf

201-kolnp-2004-granted-form 1.pdf

201-kolnp-2004-granted-form 18.pdf

201-kolnp-2004-granted-form 2.pdf

201-kolnp-2004-granted-form 3.pdf

201-kolnp-2004-granted-form 5.pdf

201-kolnp-2004-granted-gpa.pdf

201-kolnp-2004-granted-letter patent.pdf

201-kolnp-2004-granted-reply first examination report.pdf

201-kolnp-2004-granted-specification.pdf


Patent Number 218674
Indian Patent Application Number 00201/KOLNP/2004
PG Journal Number 15/2008
Publication Date 11-Apr-2008
Grant Date 09-Apr-2008
Date of Filing 16-Feb-2004
Name of Patentee BIO-DAR LTD
Applicant Address YAVNE TECHOLOGY PARK , P.O. BOX 344 81103 YAVNEM ISRAEL.
Inventors:
# Inventor's Name Inventor's Address
1 BLATT YOAV 6 TARAN STREET 76248 RE4HOVOT ISRAEL
2 PINTO RIKA 11 PINLASS STREET 62265 TEL-AVIV ISRAEL
3 SAFRONCHIK OLEG 3/16 ADAR STREET ASHDOD, ISRAEL
4 SEDLOV TANYA 25/6 MIVTSAH MOSHE 84496 DEER SHEVA ISRAEL
5 ZELKHA MORRIS 10 HADAR STR5EET OMER ISREAL
PCT International Classification Number B01J13/02
PCT International Application Number PCT/IL02/00689
PCT International Filing date 2002-08-21
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 09/935,050 2001-08-23 U.S.A.