U.S. patent application number 14/539166 was filed with the patent office on 2015-03-05 for method for preparing very low viscosity cellulose ether and product.
The applicant listed for this patent is Union Carbide Chemicals & Plastics Technology LLC. Invention is credited to Charles B. Mallon.
Application Number | 20150059619 14/539166 |
Document ID | / |
Family ID | 40254480 |
Filed Date | 2015-03-05 |
United States Patent
Application |
20150059619 |
Kind Code |
A1 |
Mallon; Charles B. |
March 5, 2015 |
METHOD FOR PREPARING VERY LOW VISCOSITY CELLULOSE ETHER AND
PRODUCT
Abstract
The present disclosure is directed to methods for producing a
very low viscosity cellulose ether having little or no
discoloration and cellulose ether products resulting therefrom. The
method includes contacting a cellulose ether with an oxidizing
agent and an acid to form a mixture. The mixture is then heated and
neutralized. The method includes adding a second oxidizing agent to
the mixture and forming a very low viscosity cellulose ether having
a viscosity from 1.2 cP to less than 2 cP. The very low viscosity
ether may also have an APHA color value of 1 to 100.
Inventors: |
Mallon; Charles B.;
(Hillsborough, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Union Carbide Chemicals & Plastics Technology LLC |
Midland |
MI |
US |
|
|
Family ID: |
40254480 |
Appl. No.: |
14/539166 |
Filed: |
November 12, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12741771 |
Aug 17, 2010 |
8920554 |
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PCT/US2008/082477 |
Nov 5, 2008 |
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14539166 |
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60986686 |
Nov 9, 2007 |
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Current U.S.
Class: |
106/172.1 ;
536/84; 536/91 |
Current CPC
Class: |
C09D 101/26 20130101;
C08B 11/20 20130101; C09D 101/28 20130101; C08L 1/26 20130101; C09D
101/284 20130101 |
Class at
Publication: |
106/172.1 ;
536/84; 536/91 |
International
Class: |
C09D 101/26 20060101
C09D101/26; C09D 101/28 20060101 C09D101/28 |
Claims
1.-14. (canceled)
15. A composition comprising: a cellulose ether wherein a 2% by
weight aqueous solution of the cellulose ether has a viscosity from
1.2 cP to less than 2 cP at 20.degree. C.
16. The composition of claim 15 comprising a coating solution of
the cellulose ether, the cellulose ether present in an amount of at
least 10% by weight of the coating solution.
17. The composition of claim 15 wherein the aqueous solution has an
APHA value from 1 to 100.
18. The composition of claim 15 wherein the cellulose ether is
hydroxypropylmethylcellulose.
19. A composition comprising: a cellulose ether wherein a 2% by
weight aqueous solution of the cellulose ether has a viscosity less
than 3 cP at 20.degree. C. and an APHA value from 1 to 100.
20. A coated composition comprising: a substrate; and a coating on
the substrate, the coating comprising a very low viscosity
cellulose ether wherein a 2% by weight aqueous solution of the
cellulose ether has a viscosity from 1.2 cP to less than 2 cP at
20.degree. C.
21. The coated composition of claim 20 wherein the coating
comprises at least 10% by weight of the very low viscosity
cellulose ether.
22.-24. (canceled)
25. The coated composition of claim 20 wherein the coating is
present in an amount from 1% to 20% by weight of the substrate.
26. The coated composition of claim 20 wherein the coating is a
single layer.
27. The composition of claim 15 wherein the aqueous solution has an
APHA value from 1 to 20.
28. A coated composition of claim 20 wherein the cellulose ether is
a hydroxypropylmethylcellulose or a methylcellulose.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. patent application
Ser. No. 60/986,686 filed on Nov. 9, 2007, the entire content of
which is incorporated by reference herein.
BACKGROUND
[0002] The present disclosure relates to methods for forming very
low viscosity cellulose ethers and cellulose ether products
resulting therefrom.
[0003] Cellulose ethers are commonly used as a film coating
material on tablets, as a food additive, and in pharmaceutical
capsules. Low molecular weight cellulose ethers oftentimes exhibit
yellowing or discoloration. It is known that as the molecular
weight of the cellulose ether decreases, the degree of
discoloration increases.
[0004] It would be desirable to develop a very low viscosity
cellulose ether with a color that is acceptable for
appearance-sensitive applications.
SUMMARY
[0005] The present disclosure is directed to methods for producing
a very low viscosity cellulose ether having little or no
discoloration and products of the same. In an embodiment, a method
for producing a cellulose ether is provided. The method includes
contacting a cellulose ether with an oxidizing agent and an acid to
form a mixture. The mixture is then heated. The mixture is
subsequently neutralized. The method includes adding at least a
second oxidizing agent to the mixture and forming a cellulose ether
having a viscosity from 1.2 cP to 50 cP when measured at 20.degree.
C. In an embodiment, the method forms a very low viscosity
cellulose ether having a viscosity from 1.2 cP to less than 2 cP
measured at 2% by weight aqueous solution at 20.degree. C.
[0006] The mixture may be heated at a temperature from 70.degree.
C. to 100.degree. C. for 1 to 20 hours. The mixture may also be
heated after addition of the second oxidizing agent under the same
parameters.
[0007] In an embodiment, the method includes maintaining the water
content of the mixture between 3% and 6% by weight.
[0008] In an embodiment, the method may be performed in an
oxygen-free environment. The oxygen-free environment may be
provided by applying an inert gas blanket to the reaction
chamber.
[0009] In an embodiment, the method includes forming a cellulose
ether having an APHA value from 1 to 100. In another embodiment the
method may include forming the cellulose ether to have an APHA
value from 1 to 20. Thus, the very low viscosity cellulose ether
may simultaneously be a very low color cellulose ether.
[0010] Another method for producing a cellulose ether is provided.
In an embodiment, this method for cellulose ether production
includes contacting a cellulose ether with a first oxidizing agent
to form a mixture. The mixture is heated. The method also includes
adding a second oxidizing agent to the mixture, and forming a very
low color cellulose ether having an APHA value from 1 to 20. This
method produces a very low color cellulose ether without the
addition of an acid. The heating may occur before the addition of
the second oxidizing agent, after the addition of the second
oxidizing agent, and combinations thereof.
[0011] In an embodiment, the method includes contacting the
cellulose ether with an acid. The acid is added along with the
first oxidizing agent, and forms a cellulose ether having a
viscosity less than about 3 cP measured at 2% by weight aqueous
solution at 20.degree. C. The mixture may be neutralized after the
heating.
[0012] In an embodiment, a method for coating a substrate is
provided. The method includes applying an aqueous solution of a
very low viscosity cellulose ether on the substrate, and forming a
coating containing the very low viscosity ether on the substrate.
The aqueous solution may have an APHA value from 1 to 100. In
another embodiment, the coating may be applied on the entire
substrate so that the coating surrounds the entire substrate.
[0013] In an embodiment, the aqueous solution contains at least 10%
by weight of the very low viscosity cellulose ether. This high
concentration cellulose ether solution is then sprayed onto the
substrate to coat the substrate.
[0014] In an embodiment, a composition is provided. The composition
may be a coating composition. The composition includes a cellulose
ether. A 2% by weight aqueous solution of the cellulose ether has a
viscosity from 1.2 cP to less than 2 cP at 20.degree. C. The 2% by
weight aqueous solution of the cellulose ether may also have an
APHA value from 1 to 100. In an embodiment, the cellulose ether is
hydroxypropylmethylcellulose. The composition may be a coating
solution. The coating solution may contain at least 10% by weight
of the cellulose ether.
[0015] In an embodiment, another composition, which may be a
coating composition, is provided. The composition includes a
cellulose ether. A 2% by weight aqueous solution of the cellulose
ether has a viscosity less than 3 cP at 20.degree. C. and an APHA
value from 1 to 100.
[0016] In an embodiment, a coated composition is provided. The
coated composition includes a substrate and a coating on the
substrate. The coating contains a very low viscosity cellulose
ether. The cellulose ether present in the coating has a viscosity
from 1.2 cP to less than 2 cP measured at 2% by weight aqueous
solution at 20.degree. C. The coating may surround the entire
substrate.
[0017] In a further embodiment, the coating contains at least 10%
by weight of the very low viscosity cellulose ether. The coating
may be a single layer. The coating may be present in an amount from
1% to 20% by weight of the substrate.
[0018] In an embodiment, the very low viscosity cellulose ether
present in the coating is a very low color cellulose ether. In an
embodiment, the coating may be transparent, clear, haze-free and/or
color-free.
[0019] An advantage of the present disclosure is the provision of
an improved method for making very low viscosity cellulose
ether.
[0020] An advantage of the present disclosure is the provision of
an improved method for making a very low color cellulose ether.
[0021] An advantage of the present disclosure is the provision of
an improved very low viscosity cellulose ether.
[0022] An advantage of the present disclosure is the provision of a
very low viscosity cellulose ether that is also a very low color
cellulose ether.
BRIEF DESCRIPTION OF THE DRAWING
[0023] FIG. 1 is a color vs. viscosity graph for conventional
cellulose ethers.
DETAILED DESCRIPTION
[0024] Any numerical range recited herein, includes all values from
the lower value and the upper value, in increments of one unit,
provided that there is a separation of at least two units between
any lower value and any higher value. As an example, if it is
stated that a compositional, physical or other property, such as,
for example, molecular weight, melt index, etc., is from 100 to
1,000, it is intended that all individual values, such as 100, 101,
102, etc., and sub ranges, such as 100 to 144, 155 to 170, 197 to
200, etc., are expressly enumerated in this specification. For
ranges containing values which are less than one, or containing
fractional numbers greater than one (e.g., 1.1, 1.5, etc.), one
unit is considered to be 0.0001, 0.001, 0.01 or 0.1, as
appropriate. For ranges containing single digit numbers less than
ten (e.g., 1 to 5), one unit is typically considered to be 0.1.
These are only examples of what is specifically intended, and all
possible combinations of numerical values between the lowest value
and the highest value enumerated, are to be considered to be
expressly stated in this application. Numerical ranges have been
recited, as discussed herein, in reference to density, weight
percent of component, tan delta, molecular weights and other
properties.
[0025] The term "composition," as used herein, includes a mixture
of materials which comprise the composition, as well as reaction
products and decomposition products formed from the materials of
the composition.
[0026] The terms "blend" or "polymer blend," as used herein, mean a
composition of two or more polymers. Such a blend may or may not be
miscible. Such a blend may or may not be phase separated. Such a
blend may or may not contain one or more domain configurations, as
determined from transmission electron microscopy.
[0027] In an embodiment, a method for producing a cellulose ether
is provided. The method includes contacting a cellulose ether with
a first oxidizing agent to form a mixture. An acid is added to the
mixture. The mixture is heated to depolymerize the cellulose ether.
The mixture is subsequently neutralized. The method includes adding
at least a second oxidizing agent to the mixture. The method
further includes forming a cellulose ether having a viscosity from
1.2 cP to 50 cP (or any value or subrange therebetween) when
measured at 2% by weight aqueous solution at 20.degree. C.
[0028] In an embodiment, the method includes forming a very low
viscosity cellulose ether. As used herein, a "very low viscosity"
(VLV) cellulose ether is a cellulose ether having a molecular
weight such that a 2% by weight aqueous solution of it at
20.degree. C. has a viscosity of from 1.2 centipoise (cP) to less
than 2 cP (or any value or subrange therebetween). It is understood
that the viscosity values set forth herein are determined according
to ASTM D1347 (methyl cellulose) and/or ASTM D2363
(hydroxypropylmethylcellulose) as measured in 2% by weight
cellulose ether aqueous solution at 20.degree. C.
[0029] As used herein, a "cellulose ether" is an ether-linked
derivative, either partial or complete, of cellulose. Cellulose
ether is produced from cellulose pulp, typically obtained from wood
or cotton. The cellulose pulp is converted into alkali cellulose by
alkalizing the cellulose pulp with an alkaline hydroxide, and then
etherifying the alkalized cellulose in a dry, gas-phase or slurry
process with one or more etherifying agents to form a high
molecular weight cellulose ether. The molecular weight of these
cellulose ethers can then be reduced by depolymerizing the
cellulose ether with an acid, such as hydrogen chloride, and
optionally neutralizing the depolymerized cellulose ether with a
basic compound, such as anhydrous sodium bicarbonate.
Alternatively, the cellulose ether may be further depolymerized by
way of acid catalyzed degradation, oxidative degradation,
degradation by high-energy radiation, and degradation by way of
microorganisms or enzymes.
[0030] The cellulose ether may be a "water soluble" cellulose ether
or a "water insoluble" cellulose ether. A "water-soluble" cellulose
ether is a cellulose ether that prior to the partial
depolymerization has a solubility in water of at least 2 grams in
100 grams of distilled water at 25.degree. C. and 1 atmosphere.
Nonlimiting examples of water soluble cellulose ethers include
carboxy-C.sub.1-C.sub.3-alkyl celluloses, such as carboxymethyl
celluloses; carboxy-C.sub.1-C.sub.3-alkyl
hydroxy-C.sub.1-C.sub.3-alkyl celluloses, such as carboxymethyl
hydroxyethyl celluloses; C.sub.1-C.sub.3-alkyl celluloses, such as
methylcelluloses; C.sub.1-C.sub.3-alkyl hydroxy-C.sub.1-3-alkyl
celluloses, such as hydroxyethyl methylcelluloses, hydroxypropyl
methylcelluloses or ethyl hydroxyethyl celluloses;
hydroxy-C.sub.1-3-alkyl celluloses, such as hydroxyethyl celluloses
or hydroxypropyl celluloses; mixed hydroxy-C.sub.1-C.sub.3-alkyl
celluloses, such as hydroxyethyl hydroxypropyl celluloses, mixed
C.sub.1-C.sub.3-alkyl celluloses, such as methyl ethyl celluloses,
or alkoxy hydroxyethyl hydroxypropyl celluloses, the alkoxy group
being straight-chain or branched and containing 2 to 8 carbon
atoms.
[0031] The cellulose ether may be a water-insoluble cellulose
ether. A "water-insoluble" cellulose ether is a cellulose ether
that prior to the partial depolymerization has a solubility in
water of less than 2 grams, or less than 1 gram in 100 grams of
distilled water at 25.degree. C. and 1 atmosphere. Nonlimiting
examples of water-insoluble cellulose ether include ethylcellulose,
propylcellulose and butylcellulose.
[0032] In an embodiment, the cellulose ether is methylcellulose,
hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethylmethyl
cellulose, hydroxypropylmethyl cellulose, hydroxybutylmethyl
cellulose, ethylhydroxyethyl cellulose, carboxymethyl cellulose,
and carboxymethyl hydroxyethylcellulose.
[0033] In a further embodiment, the cellulose ether is a
hydroxypropylmethylcellulose (HPMC) or a methycellulose (MC). HPMC
and MC are available under the METHOCEL trademark from The Dow
Chemical Company, Midland, Mich. Nonlimiting examples of suitable
HPMC and MC are set forth in Table 1 below.
TABLE-US-00001 TABLE 1 METHOCEL .TM. Products Viscosity of 2%
Methoxyl Hydroxypropyl solution in water, METHOCEL .TM. Product
Chemical Type Content, % Content, % cps METHOCEL .TM. A15
Methylcellulose, 27.5-31.5 0 12-18 Premium LV USP METHOCEL .TM. A4C
Methylcellulose, 300-560 Premium USP METHOCEL .TM. A15C
Methylcellulose, 1125-2100 Premium USP METHOCEL .TM. A4M
Methylcellulose, 3000-5600 Premium USP METHOCEL .TM. E3
Hypromellose 28-30 7-12 2.4-3.6 Premium LV 2910 METHOCEL .TM. E5
Hypromellose 28-30 7-12 4-6 Premium LV 2910 METHOCEL .TM. E6
Hypromellose 28-30 7-12 5-7 Premium LV 2910 METHOCEL .TM. E15
Hypromellose 28-30 7-12 12-18 Premium LV 2910 METHOCEL .TM. E50
Hypromellose 28-30 7-12 40-60 Premium LV 2910 METHOCEL .TM. E4M
Hypromellose 28-30 7-12 3000-5600 Premium 2910 METHOCEL .TM. E10M
Hypromellose 28-30 7-12 7500-14,000 Premium CR 2910 METHOCEL .TM.
F50 Hypromellose 27-30 4-7.5 40-60 Premium 2906 METHOCEL .TM. F4M
Hypromellose 27-30 4-7.5 3000-5600 Premium 2906 METHOCEL .TM. K3
Hypromellose 19-24 7-12 2.4-3.6 Premium LV 2208 METHOCEL .TM. K100
Hypromellose 19-24 7-12 80-120 Premium LV 2208 METHOCEL .TM. K4M
Hypromellose 19-24 7-12 3,000-5,600 Premium 2208 METHOCEL .TM. K15M
Hypromellose 19-24 7-12 11,250-21,000 Premium 2208 METHOCEL .TM.
K100M Hypromellose 19-24 7-12 80,000-120,000 Premium 2208
[0034] In an embodiment, the cellulose ether utilized in the
mixture is a high viscosity cellulose ether. A "high viscosity"
cellulose ether is a cellulose ether having a molecular weight such
that a 2% by weight aqueous solution of it at 20.degree. C. has a
viscosity greater than 400 cP, or from 400 cP to 100,000 cP. In
another embodiment, the initial cellulose ether may be a low
viscosity cellulose ether. A "low viscosity" cellulose ether is a
cellulose ether having a molecular weight such that a 2% by weight
aqueous solution of it at 20.degree. C. has a viscosity of 2
centipoise (cP) to 400 cP. In a further embodiment, the initial
cellulose ether has a viscosity greater than the viscosity of the
cellulose ether after completion of the method.
[0035] In an embodiment, the cellulose ether is a free-flowing
particulate material. The cellulose ether is ground and dried. The
average particle size for the cellulose ether may be from 20 .mu.m
to about 1000 .mu.m (or any value or subrange therebetween). The
moisture content for the initial cellulose ether is from 1% by
weight to 10% by weight (or any value or subrange therebetween), or
from 1.5% by weight to 5% by weight, or about 2% by weight of the
cellulose ether.
[0036] The cellulose ether is placed in a chamber of a reactor. The
reactor may be equipped to agitate, mix, or stir the materials
placed therein. Nonlimiting examples of suitable reactors include a
flask, an egg-shaped flask, a tumbling reactor, a ribbon blender, a
Loedige reactor, and a rotary evaporator. Any of the foregoing
reactors may be equipped with a suitable equipment to mix, agitate,
and/or stir the contents of the reactor.
[0037] The oxidizing agent is added to the cellulose ether in the
reactor to form the mixture. The oxidizing agent may be hydrogen
peroxide and salts thereof, other peroxo compounds such as, for
example, sodium peroxosulfate, ozone, perborates sodium chlorite,
halogens, halogen oxides and other compounds used for bleaching. In
an embodiment, the oxidizing agent is hydrogen peroxide. The
oxidizing agent may be added in solution form. The concentration of
oxidizing agent may range from 1% to 50% or from 30% to 40% by
weight of the solution. The oxidizing agent may be added in an
amount from about 0.01% to about 6% by weight (or any value or
subrange therebetween), or from 2% to about 4% by weight of the
cellulose ether. In an embodiment, the oxidizing agent is added so
as to maintain the water content of the mixture between 1% to 10%
by weight, or between 3% to 6% by weight of the cellulose ether. In
a further embodiment, sodium borohydride may be used in place of
the oxidizing agent (either anhydrous or in the same amount and
form as the oxidizing agent).
[0038] The method includes adding an acid to the mixture. The acid
is added to the reactor and contacts the cellulose ether to form
the mixture. Nonlimiting examples of suitable acids include any
hydrohalic acid (hydrogen chloride, hydrogen bromide, hydrogen
iodide), sulfuric acid, nitric acid and phosphoric acid. Any
combination of the foregoing acids may also be used. The amount of
acid is from 0.05% to 1%, or from 0.1% to 0.5%, based on the total
weight of the cellulose ether. In an embodiment, the acid has a pKa
less than 5.
[0039] The acid partially decomposes or otherwise depolymerizes the
cellulose ether. The acid may be added to the mixture in the
reactor in any form such as a liquid, vapor, or gas. In an
embodiment, the acid is added to the mixture in the form of an
anhydrous gas. An anhydrous gas is advantageous for a number of
reasons: 1) an anhydrous acid gas provides a high degree of
dispersion and contact with the cellulose ether; 2) introduction of
an anhydrous acid gas prevents localized concentrations of acid,
thereby avoiding tar formations in the reactor; 3) an anhydrous
acid gas avoids the addition of water to the mixture; and 4) with
no additional water added, absorption of water by the cellulose
ether product and water condensation problems in the reactor are
avoided. The anhydrous acid gas can be added to the headspace of
the reactor or directly into the cellulose ether powder. The
headspace of the reactor may be purged with an inert gas to
eliminate oxygen from the reaction chamber.
[0040] The mixture is heated to promote the depolymerization
reaction. In an embodiment, the mixture is agitated (stirred,
shaken, and/or tumbled) during the heating. The mixture is heated
to a temperature from about 70.degree. C. to about 100.degree. C.
for about 1 hour to 20 hours (or any value or subrange
therebetween), or 8 hours to 16 hours, or greater than 10 hours to
20 hours, or about 16 hours.
[0041] As the cellulose ether depolymerizes, the cellulose ether
exhibits discoloration. In other words, as the molecular weight of
the cellulose ether decreases, the discoloration of the cellulose
ether increases. Not wishing to be bound by any particular theory,
it is believed that as depolymerization proceeds, more and more
polymer end groups are formed. The increase in polymer end groups
corresponds to an increase in the number of impurities capping the
growing number of formant polymer end groups. These residual
impurities lead to discoloration. Given the relatively higher
number of end groups present in low viscosity cellulose ethers, low
viscosity cellulose ethers tend to have more discoloration than
high viscosity cellulose ethers. As one approaches the lower end of
viscosity, the increase in cellulose ether discoloration is
significant. For example, FIG. 1 illustrates the inverse
relationship between color and viscosity for various METHOCEL (E3,
E5, E6, E15, E50, and E4M) products.
[0042] It has been found that the discoloration of the cellulose
ether can be minimized by 1) performing the depolymerization
reaction in an oxygen-free environment and/or 2) limiting the water
content of the mixture during depolymerization between 1% and 10%
by weight. In an embodiment, the method is performed in an
oxygen-free environment. An oxygen-free environment may be provided
by applying an inert gas (such as nitrogen gas or a noble gas)
blanket in the reactor chamber during the depolymerization reaction
and/or during the entire production method.
[0043] Maintaining the water content of the mixture between 1% to
10% by weight (or any value or subrange therebetween) during the
depolymerization reaction (alone or in combination with an inert
gas blanket) reduces discoloration. It has been found that both (i)
a mixture having too little water content and (ii) a mixture having
too much water content each contribute to cellulose ether
discoloration. Surprisingly, maintaining the water content of the
mixture between 3% by weight to 6% by weight minimizes the amount
of discoloration during the depolymerization reaction.
[0044] The method includes neutralizing the mixture. In an
embodiment, a neutralizing agent is added to the reaction mixture.
A "neutralizing agent" is a compound that can bring the low pH of
the mixture (typically pH 1-5 after acid addition) to a pH from
about 5.0 to about 8.0. The neutralizing agent neutralizes any
remaining acid from the depolymerization reaction. The neutralizing
agent may also extract acid present in the cellulose ether.
Nonlimiting examples of suitable neutralizing agents include sodium
dihydrogen phosphate, sodium hydrogen phosphate, sodium phosphate,
sodium carbonate, sodium hydrogen carbonate, alkali salts of citric
acid, alkali salts of succinic acids and combinations thereof. In
an embodiment, the neutralizing agent is sodium bicarbonate.
[0045] Addition of the neutralizing agent ensures that the
depolymerization reaction is terminated. In an embodiment, the
neutralizing agent is an anhydrous basic powder. An anhydrous
powder is advantageous because it does not introduce water or
moisture into the mixture. For example, the neutralizing agent may
be anhydrous sodium bicarbonate powder. In an embodiment, the
neutralizing agent may have a moisture content so as to maintain
the moisture content of the cellulose ether between 1% to 10% by
weight, or between 3% to 6% by weight.
[0046] The neutralizing agent is added to the mixture by
introducing it into the reactor as commonly known in the art.
Nonlimiting examples of suitable addition methods for the
neutralizing agent include liquid injection, spraying of aerosol or
vapor, blowing of powder (i.e., by way of blowing dry powder with
compressed or forced air or other mechanical pressure). The
neutralizing agent neutralizes any acid present in the headspace
and draws out some or most acid present in the cellulose ether. In
an embodiment, the mixture is agitated as neutralization takes
place.
[0047] Neutralization can take place at a wide range of
temperatures depending upon the chemical properties of the acid and
the neutralizing agent. The neutralizing agent may be added at the
depolymerization reaction temperature. Alternatively, the mixture
may be cooled to a temperature less than the depolymerization
reaction temperature (or ambient temperature or less) prior to the
addition of the neutralizing agent to the mixture.
[0048] The method includes adding a second oxidizing agent to the
mixture. The first oxidizing agent and the second oxidizing agent
may be the same or different. The second oxidizing agent may be any
oxidizing agent as previously discussed herein. The second
oxidizing agent is added in an amount from 0.01% to 6% by weight of
the mixture (or any value or subrange therebetween), or from 2% to
4% by weight of the mixture. Upon addition of the second oxidizing
agent, the mixture may be heated to a temperature from 60.degree.
C. to 110.degree. C. (or any value or subrange therebetween), or
70.degree. C. to 100.degree. C., for 1 minute to 20 hours (or any
value or subrange therebetween), or for 1 hour to 4 hours. This
forms a very low viscosity (VLV) cellulose ether having a viscosity
of about 1.2 cP to less than 2 cP. In an embodiment, the second
oxidizing agent is added so as to maintain the water content of the
mixture between 1% to 10% by weight, or between 3% to 6% by weight.
It is understood that the method may include the addition of any
number of additional oxidizing agents (i.e., three, four, five, or
more oxidizing agents). Any subsequent oxidizing agent may be added
in a manner similar to the addition of the second oxidizing
agent.
[0049] In an embodiment, the method includes forming a cellulose
ether having an American Public Health Association (APHA) color
value from 1 to 100 (or any value or subrange therein) or from 1 to
50, or from 1 to 30, or from 1 to 20. The APHA value is determined
in accordance with ASTM D-5386 (2% concentration in aqueous
solution at ambient temperature). As used herein, a "very low
color" (VLC) cellulose ether is a cellulose ether having an APHA
value from 1 to 20 (or any value or subrange therebetween).
[0050] The present method advantageously produces a VLV cellulose
ether with low color. As previously discussed, it has been
problematic to produce VLV cellulose ether with acceptable color,
particularly for appearance-sensitive applications, such as tablet
coating. As shown in FIG. 1, as cellulose ether viscosity decreases
below 10 cP, discoloration increases dramatically. Such
discoloration makes cellulose ethers having a viscosity from about
3-5 cP or less unsuitable for appearance-sensitive applications.
The present method, however, overcomes this problem and forms a VLV
cellulose ether having surprisingly high color quality--namely, a
cellulose ether with an APHA value from 1 to 100. In an embodiment,
the APHA value for the VLV cellulose ether may be less 100. In a
further embodiment, the present method forms a VLV cellulose ether
with very low color, namely, an APHA value from 1 to 20.
[0051] In an embodiment, this method may produce a composition,
such as a coating composition. The composition includes a cellulose
ether. A 2% by weight aqueous solution of the cellulose ether has a
viscosity from 1.2 cP to less than 2 cP at 20.degree. C. (i.e., a
VLV cellulose ether). In an embodiment, the 2% by weight solution
of the cellulose ether has an APHA value from 1 to 100. In a
further embodiment, this VLV cellulose ether may also be a VLC
cellulose ether having an APHA value from 1-20. In yet a further
embodiment, the cellulose ether is hydroxypropylmethylcellulose.
The coating composition may be used to form immediate release
coatings. A nonlimiting application for immediate release coatings
is for coating orally administered tablets.
[0052] In an embodiment, the composition is a coating solution
containing the VLV cellulose ether. The VLV cellulose ether is
present in an amount of at least 10% by weight, or greater than 20%
by weight, or from at least 10% to 40% by weight (or any value or
subrange therebetween) of the coating solution.
[0053] The foregoing method may comprise two or more embodiments
disclosed herein.
[0054] In an embodiment, another method for producing cellulose
ether is provided. The method includes contacting a cellulose ether
with a first oxidizing agent to form a mixture. The mixture is then
heated. The method includes adding a second oxidizing agent to the
mixture to form a very low color cellulose ether having an APHA
value from 1 to 20. It is understood that the method may include
the addition of any number of additional oxidizing agents (i.e.,
three, four, five, or more oxidizing agents). Any subsequent
oxidizing agent may be added in a manner similar to the addition of
the second oxidizing agent. The inventors have surprisingly found
that this method utilizing a multiple-step addition of oxidizing
agent results in a cellulose ether with surprisingly high color
quality (i.e., low or no discoloration) without the necessity of
acid addition. The present method produces a VLC cellulose ether.
The VLC cellulose ether is produced without the use of an acid.
[0055] The first oxidizing agent and the second oxidizing agent may
be the same or different and may be any oxidizing agent as
previously disclosed herein. The form and amount of the first and
the second oxidizing agents may be as previously disclosed herein.
In an embodiment, the first oxidizing agent and the second
oxidizing agent are added so as to maintain the water content of
the cellulose ether from 1% to 10% by weight or between 3% to 6% by
weight.
[0056] Heating of the mixture may be performed at a point in time
(i) before addition of the second oxidizing agent (that is, after
addition of the first oxidizing agent), (ii) after addition of the
second oxidizing agent to the mixture, and (iii) any combination
thereof. Heating may occur at any temperature and/or duration as
previously discussed herein.
[0057] In an embodiment, the method can utilize an acid. In this
embodiment, the method includes contacting the cellulose ether,
with the first oxidizing agent and an acid. The acid (and the form
and the amount of the acid) may be as previously disclosed herein.
The method further includes forming a cellulose ether having a
viscosity less than about 3 cP (when measured at 2% by weight
aqueous solution at 20.degree. C.). In a further embodiment, the
method includes neutralizing the mixture after the heating.
Consequently, the method includes forming a VLC cellulose ether
having a viscosity less than 3 cP.
[0058] In an embodiment, this method may produce a composition,
such as a coating composition. The composition includes a cellulose
ether. A 2% by weight aqueous solution of the cellulose ether has a
viscosity less than 3 cP at 20.degree. C. and an APHA value from 1
to 100 (or any value or subrange therebetween). In an embodiment, a
2% by weight solution of the composition including the cellulose
ether is a VLC cellulose ether solution having an APHA value of
1-20. In yet a further embodiment, the cellulose ether is
hydroxypropylmethylcellulose.
[0059] In an embodiment, a method for coating a substrate is
provided. The method includes applying an aqueous solution of a VLV
cellulose ether on the substrate, and forming a coating on the
substrate. The aqueous solution may be applied to coat or otherwise
cover one or more surfaces of the substrate. Alternatively, the
aqueous solution may be applied to coat the entire substrate.
[0060] As used herein, a "substrate" is an object capable of being
partially or fully covered with cellulose ether. Nonlimiting
examples of suitable substrates include tablets for oral ingestion,
food products, pharmaceutical products (pharmaceutical tablets and
capsules), medicaments, drugs, seeds, animal feed, granules, beads,
powder, troches, and fertilizer. The substrate may also be an
encapsulate such as a particulate material, the particulate
material being encapsulated (micro- or macro-encapsulation) by the
coating.
[0061] Application of the aqueous solution onto the substrate may
include spraying and/or atomizing, the aqueous solution onto the
substrate. Application may also include immersing (fully or
partially) the substrate in the aqueous solution. In an embodiment,
the aqueous solution is sprayed onto the substrate.
[0062] In an embodiment, the aqueous solution of the VLV cellulose
ether has an APHA value of 1 to 100. In a further embodiment, the
aqueous solution may be a VLC cellulose ether solution having an
APHA value of 1 to 20 and have a viscosity less than 3 cP.
[0063] In an embodiment, the aqueous solution contains at least 10%
by weight, or more than 20% by weight, or between 10% to 40% by
weight (or any value or subrange therebetween) of the VLV cellulose
ether. The method further includes spraying the aqueous solution
containing at least 10% by weight VLV cellulose ether onto the
substrate to coat the substrate. In a further embodiment, the
method includes applying a single layer of the aqueous solution
containing at least 10% cellulose ether and completely coating the
substrate with cellulose ether.
[0064] In an embodiment, the aqueous solution having at least 10%
VLV cellulose ether may have coloration similar to and/or identical
to a conventional cellulose ether solution with a viscosity of 3 cP
to 6 cP. For example, the coloration for the aqueous solution with
greater than 10% by weight VLV cellulose ether at a given viscosity
may be identical to or lower than the coloration of a Methocel E3,
E5, and/or E6 solution (i.e., an APHA value from 40-60) at the same
(or lower) viscosity. In other words, the at least 10%
concentration VLV cellulose ether solution has the same or less
discoloration as conventional cellulose ether coating solutions
with lower cellulose ether concentration (i.e., conventional
METHOCEL E3, E5, E6 coating solutions). Thus the present disclosure
provides a VLV cellulose ether coating solution with (i) a higher
cellulose ether concentration and (ii) the same (or better) color
quality than conventional cellulose ether coating solutions.
[0065] The ability to spray an aqueous solution containing at least
10% weight cellulose ether is advantageous for several reasons.
Conventional film coating techniques are time consuming because
typical cellulose ether coating solutions (particularly
immediate-release film coatings) cannot contain more than 10% by
weight cellulose ether. This is because concentrations above 10% by
weight cellulose ether prevent atomization of the coating solution.
In addition, conventional cellulose ether concentration of greater
than 10% have significant discoloration, making such solutions
unsuitable for appearance-sensitive applications. The very low
viscosity of the present cellulose ether overcomes this problem.
High solution concentrations (i.e., aqueous solutions greater than
10% by weight cellulose ether) of the present VLV cellulose ether
do not experience atomization problems when the solution is
sprayed. The present VLV cellulose ether enables coating solutions
with a high concentration of cellulose ether to be applied to a
substrate using conventional applicators (i.e., atomizers and spray
devices) with no clogging and/or no obstacles to atomization.
Moreover, the present solution with at least 10% cellulose ether
has acceptable low color making it suitable for
appearance-sensitive applications.
[0066] A further advantage of the ability to spray an aqueous
solution containing more than 10% weight cellulose ether is the
production efficiencies it provides. Spraying a high concentration
cellulose ether solution delivers more cellulose ether per unit
spray than conventional cellulose ether solutions limited to 10%
weight cellulose ether concentration. The ability to apply more
cellulose ether (i) in a shorter period of time with (ii) less
coating solution provides production efficiencies by reducing the
time and materials required to coat the substrate.
[0067] The foregoing method and/or compositions may comprise two or
more embodiments disclosed herein.
[0068] In an embodiment, a coated composition is provided. The
coated composition includes a substrate and a coating on the
substrate. The coating contains a VLV cellulose ether (viscosity
from 1.2 cP to less than 2 cP). The VLV cellulose ether may have an
APHA value of 1-100. The VLV cellulose ether in the coating may
also be a VLC cellulose ether (1-20 APHA value). In an embodiment,
the dry coating is 1%-20% by weight of the substrate and is
transparent. In a further embodiment, this 1-20% by weight coating
is clear, has no color (i.e., an APHA value.ltoreq.1), or is
otherwise color-free, and/or is haze-free.
[0069] The coating may be located on a portion of the substrate. In
another embodiment, the coating surrounds the entire substrate and
encapsulates the substrate. In an embodiment, the coating is
uniform along all the surfaces (faces, sides, edges) of the
substrate.
[0070] In an embodiment, the coating includes at least 10% by
weight, or greater than 20% by weight, or between 10% to 30% by
weight (or any value or subrange therebetween), of the very low
viscosity cellulose ether. The coating is present in an amount from
1% to 20% by weight (or any value or subrange therebetween) of the
substrate. In a further embodiment, the coating is a single
layer.
[0071] The VLV/VLC cellulose ethers disclosed herein are useful in
building products, food applications, excipients for pharmaceutical
agents, cosmetics, and tablet coating for pharmaceuticals,
medicaments, dietary supplements, candies, herbal products,
over-the-counter pharmaceuticals, and drugs. The present VLV/VLC
cellulose ethers are also useful for taste masking and for flavor
fixative applications.
[0072] The coated composition may comprise two or more embodiments
disclosed herein.
[0073] By way of example and not limitation, examples of the
present disclosure will now be given.
EXAMPLES
Example 1
[0074] Add METHOCEL F4M (29.5% wt MeO, 5.7% wt HPO) to an egg
shaped flask, add anhydrous HCl by syringe and immerse the flask
while rotating in a water bath at 86.degree. C. for time indicated
in Table 2 below. Parameters for this procedure are set forth in
Table 2 below.
TABLE-US-00002 TABLE 2 30% Rxn 2% Sample Methocel Peroxide HCl,
Time, Viscosity APHA No. F4M, g. Pretreat, g g. hours (cP) Color 7
525 25 1.1 6 2.7 62 9 530 25 1.2 14 2.2 103
[0075] A nitrogen blanket is placed over the samples. Sodium
bicarbonate is added after reaction to neutralize the acid.
[0076] Sample 7 is transferred to a Loedige reactor and 10 grams of
30% hydrogen peroxide is added by spraying while the Methocel is
mixed. The reactor jacket is heated to 75.degree. C. while mixing
continued. After 3 hours, the product is removed from the reactor
and tested. APHA color is found to be 31.4.
[0077] Sample 9 (492 g) is transferred to a Loedige reactor and 20
grams of 30% hydrogen peroxide is added to it by spraying while the
product is mixed. After 5 minutes mixing, the reactor jacket is
heated to 75.degree. C. and held for 3 hours while mixing
continues. Then another 10 grams of 30% hydrogen peroxide is added
and mixing continues for 1 hour at 75.degree. C. The Methocel is
discharged and tested for viscosity and color. Viscosity is 2.17 cP
(2% solution). APHA color is 21.2.
Example 2
[0078] A pilot plant batch is made in a pilot scale tumbling
reactor under the following conditions.
[0079] Starting Methocel: F4M (29.4% wt MeO, 6.5% wt HPO)
[0080] Pounds: 10
[0081] Peroxide treatment: 91 grams of 30% hydrogen peroxide
[0082] HCl: 0.34% wt. based on Methocel
[0083] Time: 110 minutes
[0084] Temp: 95.degree. C.
[0085] Sodium Bicarbonate Added: 40 grams
[0086] Product 2% Viscosity: 1.66 cp.
[0087] Product APHA Color: 488
[0088] This product is divided into four samples then tested by
adding various amounts of 30% hydrogen peroxide to each sample in
separate smaller Loediges. This is done by spraying the peroxide
onto the product at room temperature and mixing for 10 minutes. The
samples are then removed and a portion is transferred to an egg
shaped flask. This is then rotated while immersed in a 75.degree.
C. water bath for 2 hours. APHA color is then measured on each
sample. Results are shown in Table 3.
TABLE-US-00003 TABLE 3 Grams 30% Hydrogen 2% Peroxide/100 grams
Viscosity Sample No. Methocel cP APHA Color Starting Material 0
1.66 488 1 6 1.66 143 2 8 1.66 91 3 10.5 1.66 23 4 12.9 1.66 15
Example 3
[0089] METHOCEL E4M (29.0% wt MeO, 8.5% wt HPO) is the starting
material. The samples are noticeably yellow in color to the naked
eye at the end of the LV reaction step. APHA color is not measured.
All LV reactions use 250 grams of E4M and 0.6 gram hydrogen
chloride and are carried out in a rotating round bottom flask
immersed in a water bath. Nitrogen blanketing is used in all runs.
Post treatment is performed for 3 hours at 75.degree. C. in a
rotating flask. The results are shown in Table 4 below.
TABLE-US-00004 TABLE 4 30% 30% LV LV Peroxide peroxide Reaction
Reac- 2% APHA Sam- Pretreat, post treat, Temper- tion Vis- Color
ple g/250 g g/250 g ature, Time cosity, after post No. E4M E4M
.degree. C. (hrs) cP treatment 16 5 10 75 16 1.9 14 17 5 10 75 16
1.9 13 18 5 10 75 14 1.9 12 19 5 10 87 8 1.7 12 21 5 10 87 5.5 2.2
8 22 5 10 87 5.5 1.8 16 27 5 10 87 5 2.2 7
Example 4
[0090] METHOCEL E4M, 250 grams, are added to a round bottom flask
and 0.6 grams anhydrous hydrogen chloride is added. The flask is
attached to a rotovap and immersed in a heated bath at 88.degree.
C. for 5 hours while rotating and being purged with nitrogen.
Sodium bicarbonate is then added to noticeably discolored powder
and mixed. Then 10 grams of 30% hydrogen peroxide is added and the
flask is put back on the rotovap and immersed in the bath for 2
more hours. The resulting product is tested and found to have a
solution viscosity of 2.2 cp and APHA solution color of 7.3.
Example 5
TABLE-US-00005 [0091] TABLE 5 Preparation of Very Low Viscosity
Methocel (based on 50 g Methocel E4M) 30% Anhydrous Reaction
Reaction 2% Sample Methocel Peroxide HCI Temp. Time Viscosity APHA
Nitrogen No. Moisture % Added Added .degree. C. (hr) cP Color
blanketed 53 4.1 0 0.1 g 75 16 2.2 33 Yes
[0092] Sample No. 53 is produced under the conditions shown in
Table 5. Sample No. 53 has an end viscosity of 2.2 cP and an APHA
value of 33. Then, 250 g of Sample No. 53 is added to a reactor.
Water is added to bring the moisture content up to 4.1%. 5 grams of
30% hydrogen peroxide is added before the reaction is started.
Sixteen hours of reaction at 75.degree. C., sodium bicarbonate is
added to neutralize the acid and 10 grams of 30% hydrogen peroxide
is added. The flask is returned to the rotovap and heated in the
75.degree. C. water bath for 4 more hours. Two runs are made using
this procedure, Sample No. 55 and Sample No. 57. Sample No. 55 and
Sample No. 57 are combined to provide the sample for evaluation.
The combined sample, Sample No. 58, had a 2% viscosity of 1.9 cP.
and APHA color of 10.
[0093] For purposes of United States patent practice, the contents
of any patent, patent application or publication referenced herein
are hereby incorporated by reference in their entirety herein,
especially with respect to the disclosure of structures, synthetic
techniques and general knowledge in the art. It should be
understood that various changes and modifications to the presently
preferred embodiments described herein will be apparent to those
skilled in the art. Such changes and modifications can be made
without departing from the spirit and scope of the present
disclosure and without diminishing its intended advantages. It is
therefore intended that such changes and modifications be covered
by the appended claims.
* * * * *