Note: Descriptions are shown in the official language in which they were submitted.
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IMPROVED SUCRALOSE COMPOSITION AND PROCESS
FOR THE CRYSTALLIZATION THEREOF
This is a divisional application of Canadian Patent
Application Serial No. 2,429,228 filed on November 16, 2001.
Field of the Invention
The invention relates to an improved form of sucralose and a
process for making it. It should be understood that the
expression "the invention" and the like used herein may
refer to subject matter claimed in either the parent or the
divisional applications.
Background of the Invention
Sucralose (4,1',6'-trichloro-4,1',6'-trideoxygalactosucrose)
a high intensity sweetener made from sucrose, can be used in
many food and beverage applications. Sucralose, unlike many
artificial sweeteners, can be used in cooking and baking
with no loss of sweetening power.
Sucralose is generally made following the procedures set
forth in U.S. Patent Nos. 4,362,869; 4,380,476; 4,801,700;
4,950,746; 5,470,969 and 5,498,709. In all these
procedures one of the final steps in the synthesis is a
deacylation followed by the crystallization of the
sucralose. Laboratory scale methods for crystallizing
sucralose have been described in U.S. Patent Nos.
4,343,934; 5,141,860; 4,977,254; 4,783,526; 4,380,476;
5,298,611; 4,362,869; 4,801,700; and 4,980,463. As is
described in many of these patents the deacylation of the
sucralose precursor is performed in methanol with a
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catalytic amount of sodium methoxide. After completion
of deacylation the resulting sucralose solution is
contacted with an ion exchange resin to convert the
residual sodium methoxide to methanol. The ion exchange
resin is then removed and the volatile solvents and
reaction byproducts are removed by co-distillation with
water, which results in a solvent switch to water. The
mixture is decolorized by contacting with activated
carbon. The carbon is removed to provide a decolorized
sucralose solution suitable for crystallizing sucralose.
The sucralose solution is concentrated to about 55
weight percent sucralose (at about 50 C). The
crystallization is performed by reducing the temperature
to about 22 C and adding of about 2 percent sucralose
seed crystals. The crystals that formed are separated
from the mother liquor by centrifugation then dried.
The mother liquor that is separated from the crystals is.
added to the next batch just prior to decolorization.
Unfortunately, this process has a few drawbacks.The
mother liquor can become acidic over time. Additionally,
the accumulation of impurities can interfere with the
crystallization of sucralose, resulting in the need to
periodically purge or discard the mother liquor.
Crystalline sucralose, prepared as described above,
generates minute amounts of hydrochloric acid, which
reduces the shelf life of sucralose.
It is an object of the present invention to provide an
improved process for producing a more stable form of
crystalline sucralose.
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It is another object of the present invention to provide
an . improved crystalline sucralose composition that
exhibits increased stability.
Summary of the Invention
We have discovered that addition of a buffer to the
sucralose solution before crystallization significantly
increases the stability of the sucralose crystallized
from it and also increases the stability of the mother
liquors during processing.
We have also discovered that by keeping the pH of the
sucralose containing crystallization solution in the range
of from about pH 5.5 to about pH 8.5 during the
crystallization of sucralose the final stability of
crystalline sucralose can be improved.
In another embodiment of the present invention, we have
provided a stable crystalline sucralose product that does
not develop an acetic acid odor upon storage.
In yet another embodiment of the present invention we have
provided a process for the production of a stable
crystalline sucralose product that does not develop an
acetic acid odor upon storage.
In a further embodiment of the present invention we have
also surprisingly discovered that crystalline sucralose
with residual moisture content of from about 0.5 to about
percent by weight has improved stability.
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In yet a further embodiment of the present invention we
have discovered a product comprising crystalline sucralose
in a container that will maintain the moisture content.
Preferably the container will have moisture vapor transfer
rate (MVTR) of not more than 0.25 gram water/100 square
inches of surface area /24 hours, when tested at 38 C at
92 percent relative humidity.
These inventions and other inventions' will be apparent to'
those skilled in the art from reading the following
specification (including the Examples and: Claims).
Brief Description of the Figure
Figure 1 is a flow chart of one embodiment of the
crystallization process described herein. As illustrated
in this embodiment an aqueous sucralose containing
reaction mixture is contacted with the mother liquor and
then transferred to the decolorizing tank. The mixture is
then filtered and concentrated. The concentrated
sucralose containing solution is transferred to a
crystallizer, seeded, cooled and the crystals of sucralose
are separated from the mother liquor by centrifugation.
The sucralose crystals are then dried and packaged. The
mother liquor is recycled to the beginning of this
process.
Detailed Description of the Invention
Sucralose and the methods of making sucralose have been
described in numerous patents such as US Patents Nos.
4,801,700; 4,950,746; 5,470,969 and 5,498,709,
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Following the deacylation of the protected alcohol groups in the
synthesis of sucralose, the reaction mixture containing
the sucralose needs to be neutralized, stabilized,
decolorized and the sucralose removed from the mixture by
crystallization.
The reaction mixture containing the sucralose can be
neutralized by a treatment to convert any residual
methoxide present to methanol. Conventionally this is
accomplished by the addition of an [H+] ion exchange
resin. Suitable ion exchange resins are known in the art
and include AMBERLITE IRC50 [H+] (Rohm and Haas).
To facilitate concentration and further processing of the
neutralized reaction mixture any residual volatile
solvents or reaction products are removed by distillation.
Preferably this distillation is carried out under reduced
pressure. To concentrate the neutralized reaction mixture
and water is added to obtain an aqueous solution that
contains from about 30 to about 70 percent by weight
sucralose, preferably from about 45 to about 65 percent by
weight sucralose. The reaction mixture is maintained at a
temperature sufficient to keep the sucralose in solution.
Generally the temperature will be from about 45 C to
about 50 C.
Before or after the neutralization of the sucralose
containing solution, it may be contacted with a
decolorizing agent. Most commonly the decolorizing agent
will be an activated carbon, but other decolorization
agents can also be used. The carbon may be in a powder
form or packed in a column. However, the carbon must be
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removed from the solution before crystallization. The
amount of carbon used will depend on the amount of
colorant in the reaction mixture and the type of carbon.
Those skilled in the art can readily determine the minimum
appropriate amount of carbon to add to decolorize the
mixture. The carbon can be removed by conventional means
(e.g. by filtration) if added in a loose form.
At this point a small amount of buffer salt is added to
stabilize the concentrated sucralose solution. A further
adjustment to the pH is also made to provide a neutral
solution. The buffer can be any food acceptable salts of
food acceptable weak acids such as sodium or potassium
acetate, citrate, ascorbate, benzoate, caprylate,
diacetate, fumarate, gluconate, lactate, phosphate,
sorbate, tartrate and mixtures thereof. Preferred buffer
include sodium acetate and sodium citrate which can be
used. In fact minute amounts of sodium acetate may be
present as byproduct reactions insufficient to buffer the
crystallization. The neutralization can be accomplished
using any pH adjusting acid or base compounds that will
not be inconsistent with the-use of sucralose in food or
compromise the taste of the final sucralose product.
Generally, the following pH adjusting compounds may be
used sodium, potassium, or other food acceptable salts of
hydroxide, carbonate, bicarbonate acetate, citrate,
ascorbate, benzoate, caprylate, diacetate, fumarate,
gluconate, lactate, phosphate, sorbate, tartrate and
mixtures thereof. A preferred pH-adjusting compound is
sodium hydroxide.
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We have however discovered that it is advantageous to use
small amounts of sodium acetate such that the amount of
sodium acetate in the crystallization mother liquor is
maintained at a concentration of less than 100 ppm (parts
per million) and preferably less than 50 ppm and most
preferably from about 35 ppm to about 50 ppm to ensure
that solid sucralose products do not develop an acetic
acid odor.
During crystallization the pH of the sucralose containing
solution should be maintained in the range of about 5.5 to
about 8.5 and preferably about 6.5 to about 7.8 and most
preferably about 7 to about 7.8. Maintaining the pH in
these ranges significantly enhances the long-term
stability of the sucralose product and the recycled mother
liquors.
The sucralose may be crystallized from the sucralose
containing solution using conventional crystallization
equipment. The aqueous sucralose solution is concentrated
to about 55 percent by weight sucralose content the
sucralose and is cooled to between about 10 C to about
30 C and preferably between about 20 C to about 25 C.
Preferably to induce crystal formation the aqueous
sucralose solution is seeded with sucralose seed. As a
general guideline, seed crystals comprising about 2
percent by weight of the sucralose in the crystallization
mixture appear to provide desirable crystal formation.
The crystals are separated from the mother liquor using a
centrifuge or filter and the mother liquor is recycled to
an earlier point in the process after neutralization and
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before crystallization. Preferably the mother liquor will
be recycled and added to the reaction mixture after
neutralization and before the decolorizing step.
The crystals may be washed to remove any residual mother
liquor and dried using conventional drying equipment such
as a tray or compartment dryer, agitated tray vertical
turbo dyer, agitated batch rotary dryer, fluidized bed
dryer or pneumatic conveying dryer. The dryer can be
operated at atmospheric pressure or reduced pressure in
batch or continuous modes. Experiments have unexpectedly
demonstrated that sucralose stability is enhanced if the
residual sucralose moisture content is in the range of
about 0.5 to about 10 percent by weight and preferably
from about 0.5 to about 5 percent by weight and most
preferably from about 0.5 to about 2 weight percent. The
sucralose referred to in this paragraph is non-hydrous
meaning it does not contain any significant amounts of
sucralose hydrates (e.g. sucralose pentahydrate). If the
sucralose is dried to a lower moisture content the
sucralose is actually less stable- The temperature in the
dryer should be held below 60 C and preferably in the
range of about 35 C to about 45 C.
Ideally the moisture content of the final sucralose product
will be maintained during shipping and handling between
about 0.5 to about 10 percent by weight using a package
that maintains the moisture content. The less permeable
the material is the more moisture will be retained and the
more stable the product will be. Generally the packaging
will be a container that will maintain the moisture content
of the sucralose. It is desired that the container have a
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moisture vapor transfer rate (MVTR) of not more than 0.25
gram water/100 square inches of surface area/24 hours, when
tested at 38 C at 92 percent relative humidity. Preferably
the MVTR of the container will be not more than 0.2
grams/100 square inches/24 hours. More preferably the MVTR
of the container will be not more than 0.15 grams/100
square inches/24 hours. Most preferably the MVTR of the
container will be not more than 0.1 grams/100 square
inches/24 hours. The packaging can be flexible or rigid
packaging. Suitable materials for making sucralose
packaging include but are not limited to moisture limiting
packaging such as metallized or aluminum foil laminated
substrates such as a polymer films or a kraft paper.
Suitable polymers include but are not limited to
polyolefins (such as high-density (linear) polyethylene,
polypropylene, etc.), polyesters (such as polyalkyl
terephthalates e.g. polyethylene terephthalate,
polycyclohexane-1,4-dimethylene terephthalate,
polybutylene terephthalate, etc.), polyvinyl chloride,
polyvinyl fluoride, and copolymers of polyvinyl chloride
and polyvinyl fluoride. Additionally, packaging materials
that can be used including but not limited to multi-walled
paper bags having a suitable moisture barrier, fiber drums
having polymeric or aluminum foil linings integral with the
drum wall or loose liners inserts. Rigid containers such
as blow molded drums and pails made of polymers with
moisture barriers may also be used. Flexible packages such
as shipping bags made of a polymer substrate are preferred.
Most preferred are bags made from aluminum foil laminated
to polymer films formed from polymers that are commonly
used to make moisture resistant packaging (e.g. laminates
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of aluminum foil and the polyolefins or polyesters listed
above) .
Examples
GENERAL PROCEDURES:
Preparing samples for accelerated stability testing:
Label seven 6 oz. and seven 18 oz. WHIRLPAK polyethylene
bags with indelible marker for each batch being tested for
stability. Accurately weigh 25 g 0.01 g of sucralose
into each 6 oz. WHIRLPAK polyethylene bag. Heat or
impulse seal the 6 oz. bag to ensure air tightness. Cut
off any excess polyethylene at the top of bag above the
seal. Place the 6 oz. sealed bag into the 18 oz. bag and
heat or impulse seal the 18 oz. bag to ensure air
tightness. Roll down the top of the 18 oz. bag above the
seal and bend the metal ties to form hooks.
Accelerated stability test:
Place the prepared bags into an oven stabilized at 50 C +
0.5 C by hanging them from racks by the bag hooks. The
bags must be freely suspended and not touch anything.
Record the time samples are placed into oven.
pH Stability:
The pH stability test is conducted on the sucralose at time
zero (the day the samples are placed in the oven, before
the sucralose is exposed to elevated temperature) and every
24 hours until the batch being tested fails the test.
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Preparation of pH adjusted water:
Place approximately 100 ml of deionized water into a 150
ml beaker. Using 0.1 N hydrochloric acid and/or 0.1 N
sodium hydroxide, adjust the pH of the water to be between
5.8 and 6Ø Record the pH reading.
Preparation of the sucralose sample solution:
Accurately weigh 5 g 0.001 g of the product to be tested
and transfer it to a 50 ml volumetric flask. Dissolve and
bring to the mark by adding pH-adjusted water. If the
sample to be tested is one that has been exposed to heat,
remove one bag of the batch being tested from the oven and
allow it to cool to room temperature before opening and
sampling.
Measure the PH:
Pour the solution into a 100 ml beaker containing a stir
bar, and slowly stir the solution on a magnetic stirrer.
Immerse the pH electrode in the sample, allow the pH
reading to stabilize and record the pH reading of the
sample.
If no pH drop is observed after all the bags have been
tested, the experiment is void and the test must repeated
with a larger number of bags.
Color Stability:
Only a single sample need be used for this test. Prepare
and heat the double bag as described above. Visually
inspect the contents of the single bag prepared for color
stability every 24 hours. Record the number of days to
first color development.
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CALCULATIONS AND INTERPRETATIONS:
pH Stability:
Record (to one decimal place) the pH of both the pH-
adjusted water used, and the sample sucralose solution.
Subtract the pH of the sample solution from that of the pH
adjusted water. Report the result as (-) for a pH drop
and (+) for a pH gain, e.g.:
pH of pH adjusted water 6.0
pH of sample 5.7
result - 0.3
The sample fails the test if there is a pH drop of 1.0 pH
unit or more. The pH stability of the batch is defined as
the number of days until the pH drop between the sample
solution and that of the pH adjusted water is >_ 1Ø
Color Stability:
The color stability of the batch is defined as the number
of days until the first color development is observed.
EXAMPLE 1
EFFECT OF BUFFER CONCENTRATION IN THE CRYSTALLIZATION
MOTHER LIQUOR ON PRODUCT STABILITY
A number of batches of sucralose were prepared with
varying amounts of sodium acetate in the mother liquor and
tested as.above.
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RESULTS:
Sample Sodium Acetate Initial Initial PH Days to
Number (ppm)in the pH difference pH
Mother Liquor Failure
1 > 300 5.72 - 0.20 6
2 > 300 5.73 - 0.19 6
3 > 300 5.44 - 0.48 6
4 > 300 5.64 - 0.28 6
> 300 5.64 - 0.28 6
6 > 300 5.53 0.39 4
7 > 300 5.70 - 0.22 5
8 > 300 5.19 - 0.73 5
9 > 300 6.19 + 0.23 7
> 300 5.90 - 0.05 5
11 > 300 6.05 + 0.10 6
12 > 300 5.85 - 0.10 6
13 > 300 5.85 - 0.10 5
14 35-50 5.95 + 0.02 6
35-50 6.06 + 0.13 5
16 35-50 6.20 + 0.27 6
17 35-50 6.03 + 0.10 6
18 35-50 6.00 + 0.07 6
19 35-50 6.06 + 0.13 6
35-50 6.09 + 0.08 6
21 35-50 6.05 + 0.10 6
22 35-50 6.08 + 0.09 6
23 35-50 6.12 + 0.13 5
24 35-50 6.02 + 0.03 5
35-50 6.03 + 0.05 6
26 35-50 6.06 + 0.10 6
27 35-50 5.99 + 0.03 6
28 35-50 6.00 + 0.02 6
29 35-50 6.09 + 0.12 6
35-50 5.95 - 0.02 5
31 35-50 6.03 + 0.06 5
From the tabulated data it can be seen that the average pH
stability (in days to failure) of the products
crystallized from a solution containing > 300 ppm sodium
acetate is 5.6 days. The average initial pH of those
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sample solutions was 5.7, and the average pH difference
between the sample solution and the pH-adjusted water at
time zero was -0.21 (pH drop). Several batches exhibited a
mild to strong odor of acetic acid.
For those batches crystallized from a solution containing
only 30 to 50 ppm of sodium acetate, the number of days to
failure was the same (average of 5.7 days) . The average
initial pH was 6Ø, while the average pH difference at
time zero was +0.08. None of those batches had any acetic
acid odor.
CONCLUSIONS:
The optimum level of sodium acetate in solution during the
crystallization of sucralose is 35-50 ppm. This level
proved to be sufficient to maintain the pH during the
crystallization at acceptable levels. The stability of
the final product was excellent and there was no acetic
acid odor in the product.
EXAMPLE 2
EFFECT OF PH DURING CRYSTALLIZATION ON PRODUCT STABILITY
Regardless of the amount of acetate or other buffer
substance present in the crystallization, the pH of the
mother liquor has a tendency to drop over time.
Historically, the pH has ranged from about 3 to about 4.
We have now found that if the pH is adjusted to near
neutral during crystallization, the stability of the
final product is significantly enhanced. The following
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table records the stability results of several batches
where the pH during crystallization was varied.
Sample pH at Initial pH Days to pH
Number Crystallizer difference Failure
32 2.75 - 0.90 3
33 2.97 - 0.94 4
34 2.97 - 1.03 3
35 6.28 + 0.10 5
36 5.99 + 0.04 5
37 5.99 - 0.06 5
38 6.07 + 0.17 6
39 6.07 - 0.02 7
40 7.01 + 0.40 7
41 6.13 + 0.40 5
42 6.34 + 0.17 5
43 6.13 + 0.29 5
44 7.11 - 0.18 6
45 7.17 + 0.17 7
46 8.05 + 0.43 7
It is evident from the data that controlling the pH at
near neutrality (from about 6 to about 8) significantly
increases the average stability under accelerated
stability test conditions.
EXAMPLE 3
EFFECT OF RESIDUAL MOISTURE ON THE STABILITY OF SUCRALOSE
For several batches of sucralose, samples for accelerated
stability testing were removed at intermediate moisture
levels during the drying process, and the test was
performed on the partially dried product as well as the
final dried product. Moisture levels were determined by
the loss-on-drying (LOD) procedure. The results are
tabulated in the table below.
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Initial Days to Final Days to
Sample Moisture pH Product pH
Number Content (%) Failure Moisture Failure
Content (%)
35 2.04 7 0.05 5
36 1.87 7 0.02 5
37 8.71 21 0.02 5
38 8.07 23 0.83 6
39 4.55 13 2.00 7
40 4.01 13 1.59 7
41 3.43 12 0.08 5
42. 3.16 9 0.05 5
43 5.00 8 0.02 5
These results clearly show that dry product stability is
proportional to residual moisture content. This was an
unexpected result, since most crystalline products are
much more stable when dry.
SUMMARY
While the residual moisture level exhibits the largest
influence upon product stability, it is by no means the
only important variable. It cannot overcome the effect of
lack of pH control during crystallization, for example.
This was demonstrated by the fact that experimental
samples 32, 33 and 34, crystallized with no pH control,
were actually less stable at intermediate moisture
contents (3 to 5%) than they were at their final moisture
levels (0.05, 0.11 and 0.21%, respectively).
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EXAMPLE 4
USE OF MOISTURE IMPERMEABLE CONTAINERS FOR SUCRALOSE
STORAGE
Samples of sucralose were tested for stability using the
above procedures, but using bags of different moisture
permeability. All other experimental details were the
same. The TYVEK /polyethylene bags are permeable, whilst
the WHIRLPAK bags are less permeability. The A8080 bags
consist of a aluminum foil laminated to low density
polyethylene, which makes it very impermeable to moisture.
The results are recorded below.
Sample # PACKAGE MATERIAL INITIAL PH
MATERIAL PROPERTY MOISTURE STABILITY
24 FF 91 TYVEK / Very 0.05% 4 days
Polyethylene permeable
24 WHIRLPAK Moderately 0.05% 5 days
Polyethylene permeable
24 A8080 Impermeable 0.05% 8 days
47 FF 91 TYVEK / Very 0.24% 4 days
Polyethylene permeable
47 A8080 Impermeable 0.24% 33 days
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CONCLUSION
By using impermeable packaging capable of retaining the
moisture in the bag we were able to increase the stability
of sucralose from 4 days to 33 days in accelerated
stability testing. There is a direct correlation between
the bag moisture permeability and product stability. It
is clear that other moisture impermeable materials may be
used to package sucralose and achieve this improved
stability.
