U.S. patent application number 14/285108 was filed with the patent office on 2014-09-11 for novel preparation of an enteric release system.
This patent application is currently assigned to Intercontinental Great Brands LLC. The applicant listed for this patent is Intercontinental Great Brands LLC. Invention is credited to Ahmad Akashe, Anilkumar Ganapati Gaonkar, Les Lawrence, Amado R. Lopez, Ronald L. Meibach, Dana Sebesta, Yan Wang, James D. White.
Application Number | 20140255501 14/285108 |
Document ID | / |
Family ID | 42668066 |
Filed Date | 2014-09-11 |
United States Patent
Application |
20140255501 |
Kind Code |
A1 |
Akashe; Ahmad ; et
al. |
September 11, 2014 |
Novel Preparation Of An Enteric Release System
Abstract
Hydrophobic liquids are microencapsulated by an enteric matrix
in an environment substantially free of organic solvents, the
process including forming an emulsion of the enteric material and
hydrophobic liquid in water, the emulsion titrated with an acid to
form a particulate precipitate of the microencapsulated hydrophobic
liquid in an enteric matrix.
Inventors: |
Akashe; Ahmad; (Mundelein,
IL) ; Gaonkar; Anilkumar Ganapati; (Mumbai, IN)
; Lawrence; Les; (Plainfield, IL) ; Lopez; Amado
R.; (Chicago, IL) ; Meibach; Ronald L.;
(Deerfield, IL) ; Sebesta; Dana; (Plano, IL)
; Wang; Yan; (Northfield, IL) ; White; James
D.; (Hanover Park, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Intercontinental Great Brands LLC |
East Hanover |
NJ |
US |
|
|
Assignee: |
Intercontinental Great Brands
LLC
East Hanover
NJ
|
Family ID: |
42668066 |
Appl. No.: |
14/285108 |
Filed: |
May 22, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13475645 |
May 18, 2012 |
8765030 |
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14285108 |
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12479454 |
Jun 5, 2009 |
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13475645 |
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Current U.S.
Class: |
424/490 ;
424/489; 424/757 |
Current CPC
Class: |
A61K 31/015 20130101;
A61K 31/015 20130101; A61K 36/48 20130101; A61K 31/045 20130101;
A61K 8/11 20130101; A61K 8/645 20130101; A61Q 13/00 20130101; A61K
8/927 20130101; A61K 31/045 20130101; A61K 9/5015 20130101; A61K
9/5063 20130101; A61K 2800/412 20130101; A61K 31/31 20130101; A23P
10/35 20160801; A61K 9/5052 20130101; A61K 2300/00 20130101; A61K
2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 31/05 20130101; A61K 9/0095 20130101; A61K 31/05 20130101;
A61K 31/31 20130101 |
Class at
Publication: |
424/490 ;
424/757; 424/489 |
International
Class: |
A61K 36/48 20060101
A61K036/48; A61K 9/50 20060101 A61K009/50; A61K 31/05 20060101
A61K031/05; A61K 31/015 20060101 A61K031/015; A61K 31/045 20060101
A61K031/045 |
Claims
1.-30. (canceled)
31. A composition comprising: a hydrophobic liquid; and an enteric
matrix configured to microencapsulate the hydrophobic liquid
therein, wherein the hydrophobic liquid is dispersed throughout the
enteric matrix.
32. The composition of claim 31 wherein the microencapsulated
hydrophobic liquid comprises a dry powder.
33. The composition of claim 31 wherein the enteric matrix
comprises shellac.
34. The composition of claim 31 wherein the enteric matrix
comprises zein.
35. The composition of claim 31 wherein the microencapsulated
hydrophobic liquid is coated with an enteric material.
36. The composition of claim 31 wherein the enteric matrix
comprises a combination of shellac and zein.
37. The composition of claim 36 wherein the ratio of shellac to
zein ranges from about 20:1 to 1:20.
38. The composition of claim 37 wherein the ratio is selected to
provide a desired release rate.
39. The composition of claim 37 wherein ratio of shellac to zein is
3:1.
40. The composition of claim 31 wherein the hydrophobic liquid
comprises at least one essential oil.
41. The composition of claim 31 having a particle size ranging from
about 1.0 to about 1000.0 micrometers.
42. The composition of claim 41 wherein the particle size range
from about 10.0 to about 500.0 micrometers.
43. The composition of claim 42 wherein the particle size range
from about 75.0 to about 250.0 micrometers.
44. The composition of claim 31 wherein the hydrophobic liquid
comprises from about 25.0 to about 35.0 percent by weight
para-cymene, from about 1.0 to about 10.0 percent by weight
linalool, from about 1.0 to about 10.0 percent by weight
alpha-pinene, from about 35.0 to about 45.0 percent by weight
thymol, and from about 20.0 to about 30.0 percent by weight soybean
oil.
45. The composition of claim 31 having a payload ranging from about
5.0 to about 35.0 percent.
46. The composition of claim 31 including less than about 1.0
percent by weight surface oil.
Description
FIELD OF THE INVENTION
[0001] The present application relates to methods for
microencapsulating a hydrophobic liquid with an enteric matrix
without use of organic solvents. More particularly, the hydrophobic
liquid is microencapsulated in an aqueous environment.
BACKGROUND
[0002] Enteric delivery of active materials in food delivery
applications has been limited. Enteric delivery systems are
commonly utilized when the active materials or medicants are known
to be sensitive to low pH or have undesirable flavor and/or taste
characteristics which cannot be effectively masked by other
methods. Generally, enteric delivery is accomplished using tablets
and gel capsules. However, those particular delivery methods are
not well suited for food applications. In particular, neither
tablets nor capsules are sized to be integrated into most existing
food products.
[0003] An alternative process for enteric delivery is
microencapsulation. Microencapsulation is generally performed using
specialized equipment or in an environment including organic
solvents. These methods require additional capital expenditures and
the use of additional materials, such as the organic solvents,
which may or may not be usable in subsequent microencapsulation
cycles. As a result, the process of microencapsulation requires
investments in both equipment and organic solvent procurement and
disposal.
SUMMARY
[0004] A method is provided for microencapsulating an active
ingredient within an enteric matrix in an aqueous environment and
without the use of organic solvents. Microencapsulating in an
aqueous environment allows for easier working conditions and
reduced organic waste.
[0005] A method is provided for microencapsulating an active
ingredient with an enteric matrix. The method includes agitating or
mixing a combination of water, an enteric matrix material, and an
emulsifier, at a pH that maintains complete dissolution of the
enteric polymers being utilized, the combination being
substantially free of organic solvents. A hydrophobic liquid is
then added to the combination. The hydrophobic liquid and
combination is then agitated to create a coarse emulsion, followed
by homogenization to create a fine and stable emulsion.
[0006] The emulsion can then be acid titrated under controlled
mixing conditions in an amount and a rate effective to form a
particulate precipitate. Further, the particulate precipitate can
be filtered, washed and dried to form a powder. In one embodiment a
surface oil remover can be added to the precipitate after filtering
to remove surface oil from the microencapsulated material.
[0007] Further, a composition is provided which includes a
hydrophobic liquid and a cross-linked enteric matrix.
BRIEF DESCRIPTION OF THE FIGURES
[0008] FIG. 1 illustrates a method for microencapsulating a
hydrophobic liquid;
[0009] FIG. 2 is an analysis of the products of Examples 2, 4 and
5;
[0010] FIGS. 3-5 illustrate release rates of the hydrophobic liquid
using various enteric matrix materials as discussed in Example 6;
and
[0011] FIG. 6 illustrates the release rate of the hydrophobic
liquid including esters therein as discussed in Example 7.
DETAILED DESCRIPTION
[0012] A method for microencapsulating a hydrophobic liquid is
generally described in FIG. 1.
[0013] As shown in FIG. 1, water, an enteric matrix material and an
emulsifier are subjected to agitation until the enteric matrix
material and emulsifier are fully dispersed in the water 100.
Generally, the emulsifier and enteric matrix material can be added
to the water together or separately, with either being added first.
The pH of the dispersion is generally between about 7.2 and 9.0. In
some embodiments, a base, such as sodium, ammonium or potassium
hydroxide, can be added to the dispersion to raise the pH to a
range from about 7.1 to about 12.0 to guarantee and maintain
complete dissolution of the enteric polymers without the use of
organic solvents
[0014] As used herein, "agitation" or "agitated" refers to the use
of a top entering mixer with impeller or a rotor/stator mixing
device operating at a speed of less than 10,000 RPM.
[0015] As used herein, "substantially free of organic solvent"
refers to an amount of added organic solvent, such as isopropanol
or ethanol or any other organic solvent less than the amount
required to enable solubility of the enteric material under the
processing conditions. Preferably, the amount of added organic
solvent is less than about 0.1 percent by weight of the combination
of water, emulsifier and enteric material.
[0016] In one embodiment, the water is deionized water.
[0017] The enteric matrix material used herein is any food grade
enteric polymer, of a combination or two or more food grade enteric
polymers. Preferably, the enteric matrix material is either shellac
or zein or a combination thereof. As discussed below, the ratio of
shellac to zein can be predetermined to achieve the desired release
rate after ingestion, with a decreased release rate corresponding
with an increased ratio of shellac to zein. The shellac can
commercially be provided as an alakaline (pH>7) aqueous
solution, such as a water-based solution having a solid content of
about 25 percent by weight or it can be prepared from commercially
available refined, bleached and dewaxed shellac powder. The shellac
dilution is substantially free of organic solvent, although it may
contain trace amounts of organic solvents, such as isopropyl
alcohol (such as can be included in commercial products), to act as
a carrier for other ingredients in the shellac solution, such as
methyl and propyl parabens. Preferably, the prepared shellac
solution does not contain any organic solvents.
[0018] Preferably, the enteric matrix material comprises a
combination of shellac and zein, with zein comprising at least
about 5.0 percent of the enteric matrix material by dry weight. Due
to differences in hydration and solubility of zein and shellac,
particularly the solubility at varying pHs and rates of hydration
and solubility, different ratios of shellac to zein provide
different enteric dissolution properties as well as differing
degrees of core material protection in the final product, such as
beverages.
[0019] The emulsifier described herein is any food grade
emulsifier. In preferred embodiments, the emulsifier is
polysorbate, polyglycerol ester, sucrose stearate, sucrose esters,
proteins, lecithins or combinations thereof.
[0020] Generally, water comprises about 50.0 percent to about 95.0
percent of the dispersion by weight and preferably from about 70.0
to about 95.0 percent, and more preferably from about 80.0 to about
90.0 percent. The emulsifier generally comprises less than about
5.0 percent of the dispersion by weight, preferably from about 0.01
to about 1.0 percent by weight, and more preferably about 0.01 to
about 0.1 percent by weight of the dispersion. The zein, shellac or
combinations thereof ranges from about 1.0 percent to about 10.0
percent by weight, preferably from about 4.0 to about 9.0 percent,
and more preferably from about 5.0 percent to about 8.0 percent by
weight of the dispersion.
[0021] Upon forming the dispersion, a hydrophobic liquid is added
200 and agitated to provide a coarse emulsion having a droplet size
of more than about 10 micrometers. After the coarse emulsion is
formed, the coarse emulsion is subjected to homogenization to
create a fine, stable emulsion 300. The fine, stable emulsion has a
droplet size of less than about 10 micrometers. Within the fine
emulsion, the hydrophobic liquid is homogeneously dispersed in the
form of fine droplets throughout. Preferably, the hydrophobic
liquid is added in amount ranging from about 2.0 to about 7.0
percent of the emulsion by weight. More preferably, the hydrophobic
liquid is added in an amount ranging from about 3.0 to about 6.0
percent of the emulsion by weight. The emulsion includes from about
60.0 to about 95.0 percent water.
[0022] As used herein, "homogenization" or "homogenized" refers to
the use of a rotor/stator mixing device operating at a speed
greater than 10,000 RPM or a valve homogenizer operating at a
pressure of 500-10,000 psi.
[0023] The hydrophobic liquid can comprise any mixture of
hydrophobic liquids and solids, such as solids mixed or combined
therewith or dissolved or solubilized therein. As an example,
hydrophobic liquid can be selected to include materials which are
desired to be released in the small intestine rather than the
stomach due to pH sensitivity. As an example, the hydrophobic
liquid can include compositions described in U.S. Patent
Publication No. 2008/0145462 to Enan. For example, the hydrophobic
liquid includes 25-35% by weight para-cymene, 1-10% by weight
linalool, 1-10% by weight alpha-pinene, 35-45% by weight thymol,
and 20-30% by weight soybean oil.
[0024] In particular, the hydrophobic liquid described herein can
include an essential oil blend which possesses anti-parasitic
properties. In one preferred embodiment, organic compounds are
blended with food grade oil, i.e. soybean oil. Further, the organic
compounds can include thymol and linalool. In a further preferred
embodiment, the organic compounds further include alpha-pinene and
para-cymene. As discussed in the examples below, one exemplary
blend includes, by weight, about 17.5 percent soybean oil, about 8
percent alpha-pinene (liquid), about 44 percent para-cymene
(liquid), about 5 percent linalool (liquid) and about 25.5 percent
Thymol (crystal). In an alternative embodiment, the hydrophobic
liquid includes esters, such as esters of linalool and thymol, as
described in co-pending Application Serial No. (Attorney Docket No.
94198), filed the same day as this application and which is
incorporated herein by reference.
[0025] Other suitable examples of a hydrophobic liquid include
unsaturated and polyunsaturated OMEGA 3, other unsaturated and
polyunsatured lipids or fatty acids and triglycerides thereof,
beta-carotene, and oil soluble vitamins, stomach irritants, or any
other hydrophobic materials that are either sensitive to acidic pH
conditions or impart strong undesirable taste.
[0026] The emulsion is then acid titrated 400. During acid
titration the emulsion can be subjected to agitation or
homogenization (not high pressure homogenization), preferably
agitation. Acid is titrated in an amount effective to decrease the
pH below the isoelectric point, such as a pH of about 7.0, causing
phase separation and inducing precipitation of the enteric matrix
out of solution with the hydrophobic liquid being microencapsulated
therein, thus creating a slurry of an aqueous solution and
precipitate. The slurry includes a particulate precipitate having a
particle size from about 1.0 to about 1000.0 micrometers,
preferably about 10.0 to about 500.0 micrometers, and more
preferably from about 75.0 to about 250.0 micrometers. More
preferably, precipitation occurs at a pH ranging from about 3.0 to
about 6.5, and preferably from about 3.0 to about 5.0.
[0027] While not wishing to be limited by theory, it is believed
that as the pH of the emulsion drops below the isoelectric point,
both the shellac and zein particles may cross-link to like
particles or to one another to form a matrix, the hydrophobic
liquid being microencapsulated within the matrix. As a result of
the cross-linking, the hydrophobic liquid is homogeneously
dispersed throughout the matrix. The matrix further provides a seal
for the hydrophobic liquid. As a result, the impact of the
hydrophobic liquid on the organoleptic qualities of the finished
powder is correlated to any hydrophobic liquid remaining adhered to
the outer surface of the enteric matrix.
[0028] The acid can be any food grade acid. More preferably, the
acid is a weak food grade acid. Further, in a preferred embodiment
the acid is citric acid.
[0029] As noted above, the composition of the enteric matrix
material affects the dissolution rate and the protection provided
by the enteric matrix. As a result, the rate and amount of acid
addition varies based on the enteric matrix materials used.
[0030] To reclaim the precipitate, the slurry is filtered 500,
washed 600 and dried 700. In one embodiment, the slurry is
filtered, the resultant slurry cake is then washed and refiltered
prior to drying. Preferably, the surface oil on the outer surface
of the particulate precipitate is less than about 1.0 percent by
weight of the final product.
[0031] In a preferable embodiment, a surface oil remover is added
after filtering to aid in removing residual surface oil from the
precipitate, as described in co-pending application Ser. No.
______, [ATTORNEY DOCKET 94196], filed the same day as this
application and which is incorporated herein by reference. Further,
the surface oil remover can also be added prior to the refiltering
step.
[0032] After the precipitate has been filtered and washed, the
precipitate is dried to form a powder. Drying can be conducted at
room temperature such that the powder has a moisture content of
less than about 10.0 percent, more preferably to a moisture content
of about 5.0 to about 6.0 percent.
[0033] Further, the powder can be pulverized using known methods to
reduce the particle size of the powder precipitate, and then
further dried to a moisture content of less than about 5.0 percent
by known methods, such as with a fluidized bed dryer. The resultant
particles have a particle size ranging from about 1.0 to about
1000.0 micrometers, preferably from about 10.0 to about 500.0
micrometers, and more preferably from about 75.0 to about 250.0
micrometers.
[0034] When drying the powder, the temperature should be maintained
between about 25 C to about 70 C, preferably 35 C to about 60 C,
and more preferably between 35 C and 45 C. During other processing
steps, it is preferable to maintain the temperature between about 4
C to about 40 C, more preferably 4 C to 30 C, and further
preferable from about 15 C to about 28 C.
[0035] The resultant powder can be further processed, such as
applying a coating of enteric material around the enteric matrix.
The enteric coating material can include any food grade enteric
polymer.
[0036] EXAMPLE #1
100 Percent Shellac as the Enteric Matrix Material
[0037] An essential oil blend was prepared by blending 8 percent
alpha-pinene (liquid), 44 percent para-cymene (liquid), 5 percent
linalool (liquid), 25.5 percent Thymol (crystal), and 17.5 percent
soybean oil. Mixing in a glass beaker with stirring bar was
typically carried out until all of the Thymol crystals are
dissolved.
[0038] In a large beaker the following steps were carried out in
the order specified: 1200 g of deionized (DI) water was added to
the beaker, and then 300 g of the stock solution of percent shellac
(MarCoat solution from Emerson Resources Inc.) was mixed in under
agitated conditions such that the pH of solution ranges from about
7.2 to about 9.0. While agitating, 0.8 g of polysorbate 85 was
added and mixed for 1-2 minutes for full dispersion. Next, 35 g of
essential oil blend was slowly added under agitated conditions to
form a coarse emulsion. Once the whole amount of oil was dispersed,
the mix was homogenized at 12500 rpm for 5 minutes using Fisher
Scientific PowerGen 700D Homogenizing System with 200 mm.times.25
mm Generator.
[0039] The emulsion was then subjected to agitation and, while
mixing, 2.0 percent citric acid solution was titrated in at slow
rate while monitoring the resultant change in pH. Titration
continued until the pH reached 4.4, after which SiO2 (AB-D from
Pittsburgh Plate Glass Industries) was added (5 g SiO2, in 200 g
water, and the slurry was mixed for 15-20 minutes.
[0040] The slurry was then filtered by pouring the slurry over a
200 mesh screen with 75 micrometer holes. The particulates on the
top of the screen were resuspended in 1000 g water with 3.5 g SiO2.
The slurry was mixed for 30-60 seconds and then re-filtered. The
washing was repeated one more time as above, the filtrate was
collected, spread on tray and allowed to dry at room temperature
for overnight (to a moisture content of between about 5.0 to about
6.0 percent).
[0041] A sample was analyzed for percent Payload of each component
and total.
[0042] Results: Total payload=17.5 percent
[0043] Alpha-pinene=0.7 percent
[0044] Para-cymene=3.2 percent
[0045] Linalool=1.0 percent
[0046] Thymol=7.0 percent
[0047] Soybean oil=5.6 percent
EXAMPLE 2
Scalability of the Process Using 100 Percent Shellac as a Matrix
Material
[0048] 12 kg of water was added to a mixing tank, then 3 kg of 25
percent shellac solution was added and mixed with the water, the
whole mixture was adjusted to a pH of about 8.0 by adding 10.0
percent sodium hydroxide solution. 5 g of sucrose stearate was
added and mixed for 1-2 minutes, and then 400 g of essential oil
blend (as described in Example 1) was added slowly. The mixture was
homogenized as in Example 1 to prepare a stable emulsion.
[0049] The emulsion was then titrated with 2 percent citric acid
solution until pH reached 4.4, and then 75 g of SiO2 was added and
mixed in for about 20 minutes. The slurry was then filtered using a
200 mesh (75 micrometer) screen. The filter cake was re-suspended
in 20 lb of water with 50 g SiO2, mixed for about 5 minutes, and
then re-filtered on a 200 mesh screen. The washing was repeated one
more time, and the final filter cake was spread on a large tray for
overnight drying at room temperature. The next day, the product was
pulverized in a warring blender, and then fluid bed dried at 40 C.
Collected powder was sifted through a 35 mesh (500 micrometer)
screen. (See FIG. 2 for the compositional analysis).
EXAMPLE #3
100 Percent Zein Powder (Corn Proteins) as the Enteric Matrix
Material
[0050] 75 g of zein (F4000 from Freeman Industries) powder and 1200
g of DI water was combined in a large beaker, the zein then
dispersed in the water with agitation. Once the zein powder was
completely dispersed, 10 percent sodium hydroxide solution was
slowly titrated until the pH reached 11.3. At this pH, the zein
powder was completely solubilized. Next, 0.7 g of polysorbate 85
was added, agitated for 1-2 minutes, and then 30 g of essential oil
blend (as in Example 1) was added. The mixture was homogenized as
in Example 1. The emulsion was then titrated with 2 percent citric
acid solution (as in Example 1) until pH reached 4.6. The slurry
was mixed for 15-20 minutes.
[0051] Filtering and washing was conducted as in example #1, except
no SiO2 added. Filtrate was collected and dried on a tray at room
temperature for overnight. Sample was analyzed for percent payload
of each component and total.
[0052] Results: Total payload=19 percent
[0053] Alpha-pinene=0.9 percent
[0054] Para-cymene=4.1 percent
[0055] Linalool=0.9 percent
[0056] Thymol=6.5 percent
[0057] Soybean oil=6.7 percent
EXAMPLE #4
Scalability of the Process Using 100 Percent Zein as the Enteric
Matrix Material
[0058] In a large mixing tank with propeller overhead mixer, kg of
water was added in to the tank, and then 10 g of sucrose ester
(S-1570 from Mitsubishi Kagaku Corporation, Tokyo, Japan) was
dispersed in the tank. 750 g of zein powder was dispersed in, and
then 10 percent sodium hydroxide solution was metered in while
mixing until pH reached 11.3. The dispersion was mixed until the
zein powder was completely dissolved. Next, 400 g of essential oil
blend (as in Example 1) was slowly added. Once all the oil was
dispersed, the mixture was homogenized for 5 minutes to create an
emulsion as in Example 1.
[0059] The emulsion was then titrated with 2 percent citric acid
solution under agitation until pH reached 3.8. The slurry was
allowed to mix for an extra 10 minutes. The mixture was transferred
into separate containers, allowed to stand for a few minutes so the
precipitated particulates could settle at the bottom.
[0060] The supernatant was decanted onto a large 200 mesh screen
followed by screening the remaining particulates. The filtrate on
top of the screen was re-suspended in 9 kg of acidified water (pH
3.5), containing 20 g SiO2, mixed for a few minutes and then
decanted and filtered. This washing step was repeated one more
time, the rinse water containing 20 g SiO2, after filtering the
filter cake was collected, spread thin on a tray and allowed to dry
overnight at room temperature. The semi-dry powder was pulverized
and then fluid bed dried at 40.degree. C to target moisture (less
than 5 percent). Final product was sifted through a 35 mesh (500
micrometer) screen. See compositional analysis in FIG. 2.
EXAMPLE 5
Matrix Containing 75 Percent Shellac & 25 Percent Zein
[0061] Similar to example 4, 12 kg of water was added to a mixing
tank, 7.5 g of sucrose stearate (S-1570) was added and mixed for
1-2 minutes. Then 2.25 kg of 25 percent shellac solution was added,
followed by 187.5 g zein powder. 10 percent sodium hydroxide was
metered in until pH reached 11.3 (to solubilize zein). Once the
zein powder was completely in solution, 400 g of essential oil
blend (as described in Example 1) was added. The mixture was
homogenized as in Example 1, and then the emulsion was titrated to
pH 3.9 with citric acid solution. 75 g of SiO2 (Flow Guard AB-D)
was added and mixed for about 20-30 minutes. Filtering, washing,
and drying processes were carried out in a similar fashion as
described in example 4. Final powder was sifted through 35 mesh
(500 micrometer) screen. See FIG. 2 for compositional analysis.
EXAMPLE #6
In Vitro Testing of Simulated Release in Stomach and Small
Intestine
[0062] This example is intended to show the release rate and
profile of actives from the matrix of the microcapsules from
Examples 2, 4, and 5. Release from enteric microcapsule samples was
evaluated by sequential simulation in Stomach Simulation Solution
(10 mg/ml pepsin, 2 mg/ml NaCl, pH 2.0) for 30 min followed by
Small Intestinal Simulation Solution (10 mg/ml pancreatin, 2.4
mg/ml bile salt, pH 6.8) for up to hr at 37 C. Samples were taken
at pre-determined time intervals and analyzed for release of
individual actives.
[0063] The release profile is different for the three compositions.
When the matrix was made up of 100 percent shellac (as seen in FIG.
3), the release continued to have a gradual increase but never
reached complete release even after 12 hrs. On the other hand, the
release can be characterized as having a quicker release rate and
higher total release when the matrix is made up of 100 percent zein
(about 80 percent of the total pay load is released at the first
hour in the intestinal conditions) (see FIG. 4). The combination of
the shellac and zein (See FIG. 5) show a higher rate than 100
percent shellac, but lower than 100 percent zein, and the release
seem to be sustained at a slow rate with a maximum after 6
hours.
EXAMPLE #7
This Example Demonstrates the Microencapsulation of Oil Blend
Containing Two Esterified Components (Thymol Acetate and Linalool
Acetate in Combination with Alpha-Pinene, Para-Cymene, and Canola
Oil)
[0064] In a beaker, 2400 g of water was added and then, with
agitated mixing, 7.5 g of zein powder was dispersed in the water.
10 percent sodium hydroxide solution was metered into the
dispersion until pH reached 11.3 (to solubilize the zein powder).
Next, 570 g of 25 percent shellac solution and 1.0 g sucrose
stearate (S-1570) were added, followed by 70 g essential oil blend
(18.8 percent canola oil, 8.6 percent alpha-pinene, 39.8 percent
para-cymene, 5.4 percent Linalool acetate, 27.4 percent Thymol
acetate), which was added slowly to the mix. The emulsion was then
homogenized (as in Example 1) using a Fisher Scientific PowerGen
700D Homogenizing System with 200 mm.times.25 mm Generator at 15000
rpm for 4 minutes, then at 20000 rpm for 1 minute.
[0065] The emulsion was then titrated with 3.0 percent citric acid
solution to pH 4. Then, 280 g of 10 percent sodium chloride
solution was added in, and 15 g Si02 was added and allowed to mix
for 30 minutes. The slurry was then filtered and washed similar to
that described in example #1. The washed filter cake was spread on
a tray to dry overnight, and then further dried in a fluid bed
dryer at 40 C, powder was sifted and product passing through 35
mesh (500 micrometers) size was collected. Final moisture was 4.7
percent.
[0066] The release rate is shown in FIG. 6. In particular, while
the overall release of the essential oil composition was not as
high as in FIGS. 3-5, the initial release (through 1 hour) was
lower than the compositions illustrated in FIGS. 3-5.
[0067] Analysis:
[0068] Total payload=18.3 percent
[0069] Alpha-pinene=0.9 percent
[0070] Para-cymene=3.8 percent
[0071] Linalool acetate=1.2 percent
[0072] Thymol acetate=6.6 percent
[0073] Canola oil=5.8 percent
EXAMPLE #8
Preparing Cream Wafer with Microencapsulated Essential Oil Wafer
Filling
[0074] White cream filling was prepared by mixing in a Hobart
mixer, pre-melted 750 g of San-Trans fat plus 0.5 g of liquid soy
lecithin, with confectionary sugar (powder sugar), until smooth and
homogeneous. Filling was transferred into a container and cooled
down for later use.
[0075] Wafer cracker sheets were purchased from local grocery
store. 97.8 g of cream filling was softened by warming up in a
microwave oven. To filling, the following was added: 1.46 g of
microencapsulated material, 0.15 g citric acid, 0.5 g Lemon oil
flavor, one drop of beta-carotene for yellow color. The filling was
spread on the cracker sheet (1-2 mm thick), and then another sheet
was applied onto the top. The cracker sheet sandwich was then
cooled in a refrigerator for about 30 minutes, and then it was cut
to different sizes (cracker size). A similar formulation, double
and triple layer crackers were also prepared. Other flavor
varieties were also evaluated including chocolate and fruit
flavors.
EXAMPLE 9
Cracker Sandwich with Filling Including the Microencapsulated
Material
[0076] A cracker sandwich with microencapsulated powder
incorporated into the filling was prepared as follows:
[0077] Filling:
[0078] 1) Fat portion: In a glass beaker, 2000 g of Shortening
San-Trans 39 was melted in microwave oven for about 3 minutes until
it became a clear liquid, 0.8 g of soy lecithin was added.
[0079] 2) Solid blend portion: In a Hobart mixer, the following was
dry blended: 100 g lactose, 10 g salt, and 249.4 g Maltodextrin (5
D.E.).
[0080] The melted fat was poured onto the dry blend in the Hobart
Mixer, and allowed to mix for at least 5 minutes (to form a
homogeneous mix). The filling was transferred into a container and
used as a stock filling. Cracker sandwich: 100 g of cheese filling
was warmed up in a microwave oven for 30 seconds and to the
softened filling, 1.4 g of the microencapsulated material was mixed
in, and also various seasoning and flavor blends. 18 g of the
filling was sandwiched between two crackers, and allowed to cool
down. Different flavor varieties of cracker sandwiches were
evaluated including, nacho, taco, Italian herb, and oriental
seasoning. Filling was also evaluated with different type of
crackers, including Saltine, Ritz and others. When evaluated, the
crackers containing microencapsulated essential oil were pleasantly
acceptable.
EXAMPLE 10
This Example Demonstrates the Encapsulation of the Essential Oils,
Followed by Surface Oil Removal as Disclosed in Co-Pending
Application Ser. No. ______, ATTORNEY DOCKET NO. 94196
[0081] In a beaker, 2400 g of water was added in and then with
overhead low shear mixing, 37.5 g of zein powder was dispersed in.
10% sodium hydroxide solution was metered in until pH reached 11.3
(to solubilize the zein powder). 450 g of 25% shellac solution was
added in. 1.4 g sucrose stearate (S-1570) was added in, and then 80
g essential oil blend (13% canola oil, 10% alpha-pinene, 25%
Para-cymene, 12% Linalyl acetate, 40% Thymol acetate) was added
slowly to the mix. The emulsion was then homogenized using an IKA
Works T25 Basic Ultra Turrex with 200 mm.times.20 mm Generator at
17,500 rpm for 1 minute, then at 24,000 rpm for 5 minutes.
[0082] The emulsion was then titrated with 3% citric acid solution
until the pH reached 3.8. Then, 15 g SiO2 (Flo Guard FF, average
size of 18 micrometers) was added in and allowed to mix for 30
minutes. The slurry was then filtered by pouring over a filter
cloth with <5 micrometers holes. The particulates on the filter
cloth were then resuspended into 2000 g water containing 0.5 g
citric acid, 0.5 g sucrose stearate (S-1570), and 7.5 g SiO2 (Flo
Guard FF). The slurry was mixed for 15 minutes and then
re-filtered. The washing was repeated one more time as above, then
filter cake was collected. The filter cake was then pressed by
placing in a 30 micrometers filter bag in a press box and squeezing
in a cheese press at 20 psi for 20 minutes to remove more of the
water. The press cake moisture was 18.8%.
[0083] The press cake was mixed with 50 g SiO2 (Flo Guard FF) in a
5 quart Hobart mixer with a whip at speed set at 1 for 5 minutes.
The material from the Hobart mixer was ground in a Fitz Mill Model
DA SO6 Comminutor with hammers forward at the highest speed using a
1532-0020 perforated plate. The ground material was tumbled using
jar tumblers for 60 minutes. The batch was then dried in a
Uni-Glatt Fluid Bed Dryer at 40.degree. C. for 20 minutes. The
dried batch was screened and only particles between 75-250
micrometers were collected.
TABLE-US-00001 % alpha- % para- % Linalyl % Thymyl Pinene Cymene
acetate acetate Total Total 0.84 2.70 1.50 6.40 11.44 Loading
Surface <0.001 0.007 0.003 0.021 0.031 Oils
EXAMPLE #11
Preparing a Powdered Beverage with Microencapsulated Material
[0084] Fruit flavored powdered beverages were purchased from a
supermarket, and both orange and mango type were used to prepare a
low pH powdered soft drink. Powdered soft drinks such as fruit
based type are ideal for the delivery of enteric active compounds
for several reasons: 1) The powdered drink can easily be dry
blended with microencapsulated material, and provide shelf
stability for extended period of time, 2) when reconstituted, the
beverage has an acidic pH (similar to stomach pH), no early
release, and, therefore, no adverse effect on taste, 3) Beverages
are typically consumed within a very short period of time.
[0085] The orange type powdered beverage was sweetened with sugar
and artificial sweetener and was dry blended with the
microencapsulated essential oil from example #10. A single serve
portion, such as about 7 g of orange powder, was dry blended with
0.48 g of microencapsulated powder (active payload=11.44 percent),
the amount selected to provide the desired functional benefit of
the microencapsulated hydrophobic liquid. Additionally 0.35 g of
Carboxy methyl celluolose (CMC 7HXF) was added to the dry blend to
provide extra viscosity and better suspendability. The dry blend
was reconstituted into 200 ml of cold water. The beverage was
tasted after 5 & 60 minutes after reconstitution by an informal
sensory panel. Testing by a sensory panel demonstrated successful
masking of the essential oil blend in the orange type beverage.
[0086] A similar evaluation was made with mango type beverage with
similar results.
[0087] While the invention has been particularly described with
specific reference to particular process and product embodiments,
it will be appreciated that various alterations, modifications, and
adaptations may be based on the present disclosure, and are
intended to be within the spirit and scope of the invention as
defined by the following claims.
* * * * *