Note: Descriptions are shown in the official language in which they were submitted.
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FILMS AND CAPSULES MADE FROM MODIFIED
CARBOXYMETHYLCELLULOSE MATERIALS AND
METHODS OF MAKING SAME
Field of the Invention
This invention relates to edible films and/or capsules for the delivery of
and/or
coating of active ingredients. Such edible films and/or capsules comprise
particular
molecular weight-modified carboxymethylcellulose (CMC) materials either alone
or in
combination with other types of hydrocolloids, biogums, cellulose ethers, and
the like.
The utilization of such modified CMC products aids in the production of such
films
and/or capsules through the availability of larger amounts of base materials
with lower
amounts of water requiring evaporation therefrom. In such a manner, not only
may
dimensionally stable, flexible, non-tacky, salt toleraiit, and quick
dissolving edible films
and/or capsules be produced, but the amount of time required for such
manufacture is
minimal when compared with traditional methods of production with cellulosic-
based
materials. Furthermore, such novel edible non-digestible films and/or capsules
exhibit
excellent clarity, retention of actives, and other physical properties (such
as tensile
strength, elongation, and ability to be cut into various shapes and sizes,
etc.) that make
such ultimate products attractive for use in a variety of functions.
Furthermore, such
films and/or capsules also exhibit properties in dissolution that permit
controlled release
of actives at any particularly desired rate. The novel method of film
manufacture as well
as the ultimate edible films and/or capsules exhibiting such physical
characteristics are
also encompassed within this invention.
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Background of the Invention
Films and capsules, particularly of the edible variety, have been popular for
the
delivery of active ingredients such as pharmaceuticals, breath fresheners,
oral care
materials, foodstuffs, and other like products for ingestion within a person's
oral cavity.
Furthermore, such films are utilized within coatings, seals, and other like
objects for such
materials as dyes, deodorants, detergents, tablets, and the like. Flexible
capsules have
been utilized for pharmaceutical delivery for some time now and have proven to
be
invaluable, particularly for patients that exhibit difficulty in swallowing
pills. Of more
recent development have been films that permit delivery of certain actives
(such as, as
noted above, breath fresheners, and the like) through the rapid dissolution
thereof within
the mouth of a user with concomitant absorption or other like action by the
active after
the film is removed through exposure to sufficient moisture. As other active
deliveiy
systems (chewing gum, lozenges, etc.) exhibit certain drawbacks in comparison,
such
films have increased in usage in recent years.
Such films (of the edible variety) are generally comprised of non-toxic
ingredients
that permit the desirable properties of quick dissolution, flexible film
production, and
dimensional stability for proper cutting into specific shapes and sizes.
Typical films of
this type include pullulan, cellulosics (such as hydroxypropylmethyl
cellulose),
carrageenan, pectin, as well as mixtures of certain low molecular weight
varieties of
products and high molecular weight types. Although such films have been
produced in
large-scale methods over the last few years, there are certain limitations
that are either
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aesthetically questionable to the consumer or include increased manufacturing
costs that
are passed on to the same person ultimately.
For example, clarity and low tackiness are generally properties sought after
by the
consumer. Clear, transparent films give an appearance of uniformity and order,
whereas
the utilization of a tacky film will most likely result in a film that will
dissolve only after
sticking to the user's palate for an extended period of time. Furthermore,
tackiness may
also lend itself to packed films that adhere to one another, thus increasing
the likelihood
of simultaneous use of multiple films or damage to films during removal from
the
packaging in which such products are stored. Thus, low tackiness is desirable
for such
film products.
Additionally, costs of manufacture have proven difficult to reduce for such
films,
particularly when the amount of film-forming component is relatively low.
Solutions of,
for instance, hydroxypropylmethyl cellulose (HPMC) including an excess of
about 80%
or higher by weight of water are typical for such film-forming materials. Once
the
solution is spread on a suitable plate and smoothed (such as by a blade) to a
substantially
uniform thickness, the time required to effectively form the desired film is
dependent
upon the humidity of the environment as well as the amount of water required
to be
evaporated. At such a high level of water, the needed evaporation time is
excessive or
the amount of heat needed to effectuate such evaporation quickly increases the
manufacturing costs to a rather high level. A decrease in water within the
initial solution,
although, it may reduce evaporation time ultimately, leads to other problems,
most
notably the necessity for sufficient mixing to thoroughly disperse the
cellulosic materials
throughout the solution for proper uniform film production. As such, with too
little water
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present, the amount of time and effort required for such needed thorough
mixing is
inordinately high. In either situation, the cost of manufacture is impacted by
the amount
of water needed and the ultimate cost for such film production is ultimately
passed on to
the consumer.
Thus, there has been an aim to provide edible films and/or capsules for like
delivery of actives that exhibit the same properties, at least, at lower cost
of production.
The closest prior art teaches edible, consumable films for the delivery of
certain
actives, such as flavoring and/or breath freshening agents, that are
formulated to dissolve
in the user's oral cavity. Such prior art includes films made from water
soluble polymer
such as pullulan or hydroxypropylmethyl cellulose and an essential oil
selected from
thymol, methyl salicylate, eucalyptol and/or menthol; film compositions
containing
therapeutic and/or breath freshening agents, prepared from water soluble
polymers such
as hydroxypropylmethyl cellulose, hydroxypropylcellulose, etc., and a
polyalcohol (such
as polyglycols); as well as consuinable films that comprise
hydroxyalkylmethylcellulose,
pre-gelatinized starch, and a flavoring agent.
Other teachings exist that concern the utilization of cellulosic-based
polymers for
film production; however, in each instance, the specific teaching pertains to
non-modified
(typical high molecular weight range) starting materials. As such, the films
made
therefrom, although they may exhibit effective properties for the purposes for
which they
are made, suffer from high production costs, high complexity in manufacture,
particularly
as it concerns the requirement of initially providing a tlioroughly mixed
solution prior to
film creation, as well as difficulty in ensuring all of the water witliin the
initially
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produced solution is properly evaporated during production. Relative humidity
may pose
a problem for such films and/or capsules during production as well as
thereafter (such as
during shelf storage), and polysaccharides, such as CMC,
hydroxypropylmethylcellulose,
and the like, all seem to suffer certain drawbacks as a result of water
content, not to
mention the presence of too much salt within the target environment. Thus,
there remains
a definite interest in providing the industry a film and /or capsule that is
relatively simple
to manufacture, requires very little mixing and/or evaporation of water during
production,
exhibits excellent flexibility, dimensional stability, and active retention,
and will dissolve
quickly within the target location for efficient and effective delivery of the
desired active.
As such, to date, there is a lack of teaching or fair suggestion of any such
films and/or
capsules, particularly any such products that comprise molecular weight-
modified CMC
materials. With such in mind, it has now been determined that such beneficial
films and
/or capsules are available through the utilization of particularly selected
CMC starting
materials, as well as combinations of such materials with other
polysaccharides and/or
biogums.
Brief Description of the Invention
Accordingly, it is one advantage of the present invention to provide a low-
complexity method of producing thin, non-toxic, clear films of high
flexibility and quick
dissolution in an aqueous environment. Another advantage of the present
invention is to
provide such a film and/or capsule material that exhibits such excellent
properties as
noted above, as well as effective and efficient delivery of actives
incoiporated therein.
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Accordingly, this invention encompasses a novel film and/or capsule comprising
modified CMC materials exhibiting a molecular weight range of from 1500 to
75000 and
a degree of substitution of less than about 1.5. Furthermore, this invention
encompasses
a metliod of producing such a film and/or capsule comprising the steps of a)
providing a
CMC materials exhibiting a molecular weight range of from 80000 to 3000000 and
degree of substitution of less than about 1.5; b) degrading said CMC materials
by
exposing said materials to an enzyme in an amount and for a period of time
sufficient to
reduce the molecular weight range of said CMC materials to a range of from
1500 to
75000; c) inactivating said enzyme; d) producing a solution of the resultant
modified
CMC materials of step "b" with at most 70% by weight of water and optionally
including
at most 12.5 % of a plasticizer; and e) forming a film or capsule through
proper
application of said solution to a proper surface and allowing said water
therein to
evaporate therefrom. Such films thus exhibit at least the same film strength,
rapid film
dissolution, and delivery capabilities of active ingredients as previously
made films
and/or capsules, but with lower manufacturing costs, and potentially reduced
tackiness as
those currently utilized within the pertinent markets. Such an improvement has
been
realized through the utilization of a single modified CMC component as well,
thereby
permitting a reduction in manufacturing complexity of films. Such is a
significant benefit
over the comparative prior film compositions that have relied upon
combinations of
ingredient polymers to provide similarly effective films and/or capsules.
Although a
single modified CMC polymer may be utilized for this application, it is noted
that
combinations of the required modified CMC polymer with other polymeric
additives,
sucli as hydrocolloids, biogums, and cellulose ethers (either ge1-forming or
non-gelling
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viscosity building types, depending on the potential benefits desired from
such an
additive) may be practiced as well. Such a film and/or capsule, of the
modified CMC
alone or in combination with such other optional gel-forming or non-gelling
viscosity
building additives is thus highly desired from a cost perspective as well as
quick and
coinplete dissolution when exposed to sufficient moisture within the oral
cavity. Such a
specific characteristic is advantageous since undissolved film residue imparts
an
unacceptable, unpalatable, slimy feel to the palate of the user.
Summary of the Invention
For the purpose of this invention, the term "film" is intended to encompass a
solid, flexible sheet of polymer material that has a very low ratio of
thickness to area
(width multiplied by length).
The term "capsule" is intended, for purpose of this invention, to encompass a
flexible container that may be used to carry and active material into the
digestive tract for
later delivery of this active agent.
Polysaccharides, such as certain cellulosic-based types
(carboxymethylcellulose,
as one non-limiting example), have been utilized within numerous fields for
many years
as viscosity modifiers, carriers, anti-redeposition agents, and other like
purposes within
the paper, oil, food, paint, and detergent industries, to name a few. The
benefits of
modified cellulosics water-soluble polymers have been provided as well,
particularly
within U.S. Pat. No. 5,569,483 to Timonen et al., as it pertains to
substitution of fat
within foodstuffs, and within U.S. Pat. No. and 5,543,162 to Timonen et al.,
as it pertains
to the utilization of such enzymatically lnodified cellulosics in combination
with
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hydrophilic polymers (such as gelatin) in coacervation methods of forming
capsules.
There is no discussion within either of these references of the ability of
specific modified
CMC materials for the purpose of providing excellent film, capsule, or other
type of
coating, particularly those that meet certain molecular weight and thus
viscosity
requirements.
The present invention relates to an edible film composition comprising a safe
and
effective amount of at least a modified CMC material, optionally, a further
amount of
another polysaccharide or biogum material, optionally, a safe and effective
amount of a
plasticizing agent, and, a safe and effective amount of an ingredient,
including, as
examples, a flavoring agent, a pharmaceutical agent, an oral care additive, an
anti-
inflammatory agent, an antimicrobial agent, a surfactant, a sweetener, a
vitamin, and the
like. The films of this invention may be utilized as delivery systems for such
active
ingredients through dissolution within the oral cavity of a user and/or
patient, or as a
coating or seal for materials including, without limitation, foodstuffs,
soaps, detergents,
tablets, and the like, or potentially can be modified to form capsules for
transport of
active ingredients to the oral cavity of a user and/or patient (delivery of
actives in
capsules takes place in the stomach/gastro-intestinal system).
Detailed Description of the Invention
All percentages and ratios used hereinafter are by weight of total
composition,
unless otherwise indicated. As used herein, percentage by weight of the film
composition
means percent by weight of the wet film composition, unless otherwise
indicated.
All U.S. patents cited herein are hereby incorporated in their entirety by
reference.
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.. ..... ..
The edible film and/or capsule compositions of the present invention comprise
at
least one molecular weight-modified CMC material. Although such degradation
may be
accomplished through any type of well known method, such as acid, radiation,
oxidation
and heat degradation, preferably the degradation step is provided through
enzymatic
exposure. Thus, the initial method step is actually providing the degrading
CMC material
for further use thereof. Such a step may be accomplished similarly to that
taught within
either of the Timonen et al. patents discussed above. In essence, a CMC having
the
desired degree of substitution and initial molecular weight is subjected to a
preselected
amount of cellulase enzyme in order to reduce the overall molecular weight of
the CMC
material itself to a level proper for film and/or capsule production. The CMC
selected for
this step, as alluded to above, must exhibit a proper degree of substitution
(i.e., the
average amount of carboxymethyl groups per glucose unit) in order to permit
the ultimate
generation of a film and/or capsule exhibiting the requisite characteristics
of rapid
dissolution, dimensional stability, and low tackiness, at least. For certain
end uses, such
as those involving ingestion as or in tandem with foodstuffs, the degree of
substitution is
preferably, though not necessarily, lower than about 0.95. For other types of
end uses,
higher levels may be permitted (such as up to about 1.5). The initial
molecular weight
may be within a broad range as long as the ultimate molecular weight range
meets the
requirements that lead to the sai-ne type of proper film and/or capsule
generation in terms
of the physical characteristics noted above. Thus, an initial molecular
weiglit range, as
measured as by using GPC analysis of from 80,000 to about 3,000,000 is
acceptable. The
thus preselected CMC starting material caii then be exposed to an amount of
cellulase
that coincides, in combination with the amount of time of such exposure, pH
and
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temperature with the ultimate degradation of the CMC material into individual
strands
thereof exhibiting a range of molecular weights from 1,500 to 75,000. If the
molecular
weight is too low (below 1,500), then the film or capsule will be too friable
to properly
function. Preferably, though not necessarily, the molecular weight will be
between about
20,000 and 50,000 for the modified CMC materials. A lower molecular weight
range
(i.e., from 1,500 to about 20,000) may be utilized as well, but will
preferably, though,
again, not necessarily, be compensated for witll a higher degree of
substitution. After the
time of enzyme exposure is completed, the cellulase can then be inactivated
through heat
exposure, as one example, thereby preventing further degradation of the CMC
from
occurring. The enzyme can be removed from within the modified CMC solution
used for
film and/or capsule production.
The molecular weight range sought after for the modified CMC materials
transfers to a viscosity measurement for the solutions used to ultimately
produced the
target films typically within a range of 10,000 mPas to 45,000 mPas. It has
been found as
well that such viscosity measurements appear to contribute to the overall
effectiveness of
the ultimately formed films and/or capsules in combination with the degree of
substitution of the starting CMC materials themselves. Thus, it has been
determined that
such molecular weight and viscosity properties are critical to the success of
the overall
invention, at least when the sole film-forming component of the solution is
the modified
CMC material.
As noted previously, one surprising result of this invention is that the
modified
CMC can be utilized as such a sole film-forming component. Most commercially
available films require the utilization of combinations of different polymers
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desired film properties; however, it has surprisingly been determined that the
modified
CMC polymers utilized within this invention are sufficient on their own to
achieve such
results. The ability to form a film and/or capsule that meets or exceeds the
aforementioned physical characteristics as well as can withstand certain salt
and relative
humidity exposures without appreciably effecting the dimensional stability and
usefulness of the ultimate end use product was unexpected. If desired,
however, one may
include other hydrocolloids, biogums, and/or cellulose ethers to provide
increases in salt
and/or humidity protection, or to provide viscosity build within film- and/or
capsule-
formulations, or to provide gel formation for the same types of formulations,
and/or one
may include a plasticizer in order to increase film flexibility or provide
increases in
dimensional stability and other physical characteristics of the subject films
and/or
capsules as well. Such a molecular weight-modified CMC polymer exhibits
excellent
compatibility with such other possible polymers and thus their optional
presence should
not be problematic.
The other types of optional polymeric additives that may be utilized within
the
inventive films and/or capsules, again, in addition to the required modified
CMC
materials, include, without limitation, non-gelling viscosity building
additives selected
from the group consisting of cellulose ethers, such as methyl cellulose, (non-
modified)
carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose,
hydroxypropylmethylcellulose, and mixtures tliereof; biogums, such as xanthan
gum,
diutan gum, rhamsan gum and welan gum, gellan gum, and mixtures thereof; and
hydrocolloids such as caiTageenan, pectin, gum arabic, guar, locust bean gum,
gum
tragacanth, tara gum, sodium alginate, acacia gum, pullulan, pustulan,
scleroglucan, and
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mixtures thereof; and any combinations or mixtures thereof such different
types of
hydrocolloids. Furthermore, other additives that impart gel-forming
characteristics to the
modified CMC formulations include, without limitation, gel-forming additives
selected
from the group consisting of of gellan gum (high and low acyl forms),
carrageenan
(kappa and iota types), xanthan/locust bean gum, sodium alginate, curdlan,
MHPC,
pectin, and any combinations or mixtures thereof. The optional polymeric
additives
listed above may be present therein in an amount of from 0.05 to 50% by weight
of the
entire film and/or capsule.
One benefit of utilizing the modified CMC, particularly, whether alone or in
combination with these other types of hydrocolloids and/or biogums, is the
reduced
viscosity exhibited thereby permits greater amounts of the modified CMC to be
introduced within the film-forming solution than is customary. As discussed
above, this
permits a reduction in the amount of water needed for a proper film-forming
coinposition
to be produced and drastically reduces the time required for water
evaporation.
Furthermore, the film-forming solution can be easily and thoroughly mixed
under
relatively low energy levels such that a properly dispersed solution is
accorded the film
producer as well. The modified CMC materials are present as long strands,
rather than as
coiled globules of CMC; thus, the avoidance of detrimental lumps within the
film-
forming solution is possible at the aforementioned low energy mixing levels.
The proper
film-forming solutions thus will comprise from about 10 to about 50% of the
modified
CMC, from about 50 to about 90% by weight of water, and optionally, from 0 to
about
12.5% by weight of a plasticizer. The active ingredient is also incorporated
within the
film-forming solution and is thoroughly mixed therein as well for proper
dispersion
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within the ultimate film. Such an additive may be present in an amount of from
about
0.001 to about 70% by weight of the entire composition.
In addition to the above essential modified CMC film-forming agents, the
solution may also comprise other additional film-forming agents other than the
hydrocolloids, cellulose ethers, and/or biogums listed above, such as, without
limitation,
polyvinyl pyrrolidone, polyvinyl alcohol, sodium alginate, polyethylene
glycol,
polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, starch,
amylose,
high amylose starch, hydroxypropylated high amylose starch, dextrin, , chitin,
chitosan,
levan, elsinan, collagen, gelatin, zein, gluten, soy protein isolate, whey
protein isolate,
casein, and mixtures thereof.
The compositions of the present invention also coinprise a safe and effective
amount of a plasticizing agent to improve flexibility and reduce brittleness
of the edible
film composition. Suitable plasticizing agents of the present invention
include, but are
not limited to, polyols (such as sorbitol; glycerin; polyethylene glycol;
propylene glycol;
acetylated monoglyceride; hydrogenated starch hydrolysates; corn syrups; and
derivatives
thereof; xylitol; glycerol monoesters with fatty acids; triacetin; diacetin;
and monoacetin)
and mixtures thereof. In one embodiment the plasticizing agent of the present
invention
is glycerol.
The compositions of the present invention may also coinprise a safe and
effective
amount of an additive selected from the group consisting of a flavoring agent,
an
antimicrobial agent, an oral care and/or a phazmaceutical agent, a surfactant,
a sweetener,
a nutrient (such as a vitamin or mineral), and any coinbinations thereof.
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Suitable flavoring agents include any well known food flavoring (of which
there
are a vast variety to choose from) including, without limitation, examples
such as oil of
wintergreen, oil of peppermint, oil of spearmint, clove bud oil, menthol,
eucalyptol,
lemon, orange, cinnamon, vanillin, and the like, and mixtures thereof. In
another
embodiment, in order to stabilize the flavor, the compositions may optionally
comprise a
vegetable oil.
The present invention may optionally comprise a safe and effective amount of
an
oral care active agent and/or a pharmaceutical active agent. The oral care
active agent
suitable for use herein is selected from the group consisting of anticalculus
agent, fluoride
ion source, antimicrobial agents, dentinal desensitizing agents, anesthetic
agents,
antifungal agents, anti-inflammatory agents, selective H-2 antagonists,
anticaries agents,
nutrients, and mixtures thereof. The oral care active agent preferably
contains an active
at a level where upon directed use, the benefit sought by the user is promoted
without
detriment to the oral surface to which it is applied. Examples of the "oral
conditions"
these actives address include, but, are not limited to, appearance and
structural changes to
teeth, whitening, stain removal, plaque removal, tartar removal, cavity
prevention and
treatment, inflamed and/or bleeding gums, mucosal wounds, lesions, ulcers,
aphthous
ulcers, cold sores, tooth abscesses, and the elimination of mouth malodor
resulting from
the conditions above and other causes such as microbial proliferation.
Suitable oral care
actives include any material that is generally considered safe for use in the
oral cavity and
that provides changes to the overall appearance and/or health of the oral
cavity. The level
of oral care substance in the compositions of the present invention is
generally, unless
specifically noted, from about 0.01% to about 50 10, preferably from about
0.1% to about
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20%, more preferably from about 0.5% to about 10%, and even more preferably
from
about 1% to about 7%, by weight of the dry film composition.
The anticaries agent may be selected from the group consisting of xylitol,
fluoride
ion source, and mixtures thereof. The fluoride ion source provides free
fluoride ion
during the use of the composition. In one embodiment the oral care active
agent is a
fluoride ion source selected from the group consisting of sodium fluoride,
stannous
fluoride, indium fluoride, organic fluorides such as amine fluorides and
sodium
monofluorophosphate. Sodium fluoride is the fluoride ion in another
embodiment. In
one embodiment the anticalculus agent is selected from the group consisting of
polyphosphates and salts thereof; diphosphonates and salts thereof; and
mixtures thereof.
In another embodiment the anticalculus agent is selected from the group
consisting of
pyrophosphate, polyphosphate, and mixtures thereof.
The anticalculus agent is a polyphosphate, understood to mean a coinpound
consisting of two or more phosphate molecules arranged primarily in a linear
configuration, although some cyclic derivatives may be present. Counterions
for these
phosphates may be the alkali metal, alkaline earth metal, ammonium, C2-C6
alkanolainmonium and salt mixtures. Polyphosphates are generally employed as
their
wholly or partially neutralized water soluble alkali metal salts such as
potassium, sodium,
ammonium salts, and mixtures thereof. The inorganic polyphosphate salts
include alkali
metal (e.g. sodium) tripolyphosphate, tetrapolyphosphate, dialkyl metal (e.g.
disodium)
diacid, trialkyl metal (e.g. trisodiunl) monoacid, potassium hydrogen
phosphate, sodium
hydrogen phosphate, and alkali metal (e.g. sodium) hexametaphosphate, and
mixtures
thereof. Polyphosphates larger than tetrapolyphosphate usually occur as
ainorphous
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glassy materials. In one embodiment the polyphosphates are those manufactured
by FMC
Corporation which are commercially known as Sodaphos, Hexaphos, and Glass H,
and
mixtures thereof.
Pyrophosphate salts may be utilized in a like manner to the polyphosphates
noted
above. Such would include alkali metal pyrophosphates, di-, tri-, and mono-
potassium or
sodium pyrophosphates, dialkali metal pyrophosphate salts, tetraalkali metal
pyrophosphate salts, and mixtures thereof. More specifically, these may be, in
non-
limiting fashion, trisodium pyrophosphate, disodium dihydrogen pyrophosphate,
dipotassium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium
pyrophosphate,
and mixtures thereof. Optional agents to be used in place of or in combination
with the
pyrophosphate salt include such known materials as synthetic anionic polymers,
including polyacrylates and copolymers of maleic anhydride or acid and methyl
vinyl
ether (e.g., Gantrez), as described, for example, in U.S. Pat. No. 4,627,977,
to Gaffar et
al., the disclosure of which is incorporated herein by reference in its
entirety; as well as,
e.g., polyamino propoane sulfonic acid (AMPS), zinc citrate trihydrate,
polyphosphates
(e.g., tripolyphosphate; hexametaphosphate), diphosphonates (e.g., EHDP; AHP),
polypeptides (such as polyaspartic and polyglutamic acids), and mixtures
thereof.
Antimicrobial antiplaque agents may also by optionally present in the present
compositions. Such agents may include, but are not limited to, triclosan, 5-
chloro-2-(2,4-
dichlorophenoxy)-phenol, chlorhexidine, alexidine, hexetidine, sanguinarine,
benzalkonium chloride, salicylanilide, domiphen bromide, cetylpyridinium
chloride
(CPC), tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium
chloride
(TDEPC), octenidine, delmopinol, octapinol, and other piperidino derivatives;
effective
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antimicrobial amounts of essential oils and combinations thereof for example
citral,
geranial, and combinations of menthol, eucalyptol, thymol and methyl
salicylate;
antimicrobial metals and salts thereof for example those providing zinc ions,
stannous
ions, copper ions, and/or mixtures thereof; bisbiguanides, or phenolics;
antibiotics such as
augmentin, amoxicillin, tetracycline, doxycycline, minocycline, and
metronidazole; and
analogs and salts of the above antimicrobial antiplaque agents; anti-fungals
such as those
for the treatment of candida albicans.
Anti-inflammatory agents may also be present in the oral compositions of the
present invention. Such agents may include, but are not limited to, non-
steroidal anti-
inflammatory agents such as aspirin, ketorolac, flurbiprofen sodium,
ibuprofen,
acetaminophen, diflunisal, fenoprofen calcium, naproxen, indomethacin,
ketoprofen,
tolmetin sodium, piroxicam and meclofenamic acid, COX-2 inhibitors such as
valdecoxib, celecoxib and rofecoxib, and mixtures thereof.
The present invention may also include a safe and effective amount of a
selective
H-2 antagonist such as, without limitation, cimetidine, etintidine,
ranitidine, tiotidine,
lupitidine, donetidine, famotidine, roxatidine, pifatidine, lamtidine,
zaltidine, nizatidine,
mifentidine, ramixotidine, loxtidine, bisfentidine, sufotidine, ebrotidine,
and
impromidine.
Nutrients include minerals, vitamins, oral nutritional supplements, enteral
nutritional supplements, and mixtures thereof. Minerals that can be included
with the
compositions of the present invention include calcium, phosphorus, fluoride,
zinc,
manganese, potassium and mixtures thereof. Vitamins can be included with
minerals or
used separately. Vitamins include Vitamins C and D, thiamine, riboflavin,
calcium
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pantothenate, niacin, folic acid, nicotinamide, pyridoxine, cyanocobalamin,
para-
aminobenzoic acid, bioflavonoids, and mixtures thereof. Oral nutritional
supplements
include amino acids, lipotropics, fish oil, and mixtures thereof. Amino acids
include, but,
are not limited to L-Tryptophan, L-Lysine, Methionine, Threonine,
Levocarnitine or L-
carnitine and mixtures thereof. Lipotropics include, but, are not limited to
choline,
inositol, betaine, linoleic acid, linolenic acid, and mixtures thereof. Fish
oil contains
large amounts of Omega-3 polyunsaturated fatty acids, eicosapentaenoic acid
and
docosahexaenoic acid. Antioxidants that may be included in the oral care
composition or
substance of the present invention include, but are not limited to Vitamin E,
ascorbic
acid, Uric acid, carotenoids, Vitamin A, flavonoids and polyphenols, herbal
antioxidants,
melatonin, aminoindoles, lipoic acids and mixtures thereof. Enteral
nutritional
supplements include, but, are not limited to protein products, glucose
polymers, corn oil,
safflower oil, and medium chain triglycerides.
Anti-pain or desensitizing agents and anesthetic agents can also be present in
the
oral care compositions or substances of the present invention. Such agents may
include,
but are not limited to, strontium chloride, potassium nitrate, natural herbs
such as gall nut,
Asarum, Cubebin, Galanga, scutellaria, Liangmianzhen, Baizhi, etc. Anesthetic
agents
include lidocaine, benzocaine, etc.
The pharmaceutical active agent suitable for use herein is selected from the
group
consisting of sedatives, hypnotics, antibiotics, antitussives,
antihistainines, non-sedating
antihistamines, decongestants, expectorants, mucolytics, antidiarrheals,
analgesics-
antipyretics, proton pump inhibitors, general nonselective CNS stimulants,
drugs that
selectively modify CNS function, antiparkinsonism drugs, narcotic-analgesics,
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psychopharmacological drugs, laxatives, dimenhydrinates, and mixtures thereof.
Preferred pharmaceutical actives suitable for use as an active ingredient
herein include
antitussives, antihistamines, non-sedating antihistamines, decongestants,
expectorants,
mucolytics, analgesics-antipyretics, anti-inflammatory agents, antidiarrheals,
and
mixtures thereof.
Suitable surfactants are those which are reasonably stable and include
nonionic,
anionic, amphoteric, cationic, zwitterionic, synthetic detergents, and
mixtures thereof.
The present compositions may optionally comprise sweetening agents including
sucralose, sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol,
sorbitol,
fructose, maltose, xylitol, saccharin salts, thaumatin, aspartame, D-
tryptophan,
dihydrochalcones, acesulfame and cyclainate salts, especially sodium cyclamate
and
sodium saccharin, and mixtures thereof.
Coolants, salivating agents, warming agents, coloring agents, and numbing
agents
can be used as optional ingredients in compositions of the present invention
as well.
Preferred Embodiments of the Invention
The film compositions utilized in accordance with the invention are formed by
processes conventional in the arts, e.g. the paper-making and/or film making
industries.
Generally the separate components of the film are blended in a mixing tank
until a
homogeneous mixture is achieved. Thereafter, the films can be cast to an
acceptable
thickness, on an appropriate substrate. Examples of such substrates include
Mylar,
continuous moving stainless steel belt (eventually entering a dryer section),
release paper
and the like. The webs are then dried, e.g. in a forced-air oven. The
temperature of the
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drying air and length of drying time depend on the nature of the solvent
utilized as is
recognized in the art. Most of the films contemplated herein, however, are
dried at a
temperature between about 25 C (i.e., ambient temperature) and 140 C (with a
lower
temperature preferred to reduce costs), for a duration of about 20 minutes to
about 60
minutes, in another embodiment from about 30 to about 40 minutes. Drying of
these
films should be carried out in a way that moisture gradients are minimized in
the film.
Such gradients come from rapid drying and lead to curling and lack of
dimensional
stability. When dried properly, the films will have a final water activity of
0.5 (+/- 0.25)
so that they do not either take up or lose significant amount of water when
exposed to
normal ambient conditions. The moisture content will vary depending upon the
composition of the film, it's water activity rather than water content that is
the parameter
to be controlled. Films with a low water content may be dried in as little as
30 minutes at
40 C. The optimal temperature of the film during drying is usually lower than
65C .
Higher temperatures can be used, especially if the film is dried
simultaneously from the
top and bottoin. This can be accomplished by using a heated metal belt of the
bottom and
indirect intra-red heating from above. Microwave techniques and other novel
drying
technologies can also be used successfully. After exiting from the dryer
section of the
casting belt, the film can be wound on a spool for storage under sanitary
conditions. The
film can be slit into two inch rolls for further cutting to form 1 inch by 2
inch (or other
desired dimensions) and then stacked and subsequently individually packaged.
Extrusion is also a possible method of film manufacture. The mechanical
particulars of the extrusion process, e.g. the particular equipment utilized,
the extruding
force, the shape and teinperature of the orifice are considered to be within
the skill of the
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art and can be varied in a known manner to achieve the physical
characteristics of the
films described herein.
The films herein are generally between about 1 and about 10 mils (about 0.025
mm to about 0.25 mm), in another embodiment are from about 1.2 to about 2.5
mils
(about 0.03 mm to about 0.064 mm) thick. A convenient width for such films is
about
0.75 to about 1 inch, although the width of the film is not particularly
critical to the
practice of the invention. The film can be produced in any length. However, in
view of
the fact that the novel dosage forms produced in accordance with the invention
are suited
to high speed manufacture, the films should be prepared in large quantity,
e.g. 15,000 feet
or more which can be stored, e.g. on cores or spools.
Likewise, the capsules made therefrom may be produced through typical capsule-
making procedures utilizing the same basic solutions as the film-inaking
methods. The
required modified CMC may be applied in hard (two-piece) and/or soft (one-
piece)
capsules. The term "hard capsules" connotes that such materials must retain
their shape
from the time of manufacture through being filled and ultimately until they
are ingested
for use. "Soft capsules", however, exhibit a soft shell only at the momeilt
they are
formed and filled. One-piece capsules are generally sold as forinulated
products whereas
hard capsules are generally manufactured empty and filled at a later time.
Gelatin has traditionally been the material of choice within the capsule
industry.
Gelatin exhibits a nutnber of properties that inake such a material a proper
candidate for
capsule manufacture including good film forming properties (strength and
flexibility,
primarily), good solubility in biological fluids at typical body teinperature,
low viscosity
at 50 C at high solids concentrations, and a gel state at low temperatures.
Likewise,
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methylhydropropyl cellulose has recently found favor within the capsule
industry for the
same basic reasons.
Soft capsules containing gelatin are made by passing two flexible sheets of
gelled
plasticized gelatin solution between a pair of rotating cylinders. The gelatin
sheets are
passed over and are sealed together by mechanical pressure and heat. The films
are half
sealed before the filling process starts. The cylinders have cavities in their
surfaces and
the gelatin sheet is forced into their shape by the pressure of the ffill
material as it is
pumped between the cylinders. Subsequent to such a step, the resultant
capsules are then
dried. As alluded to above, the gelatin solution requires a significant
quantity of
plasticizer to form the necessary flexible sheets for introduction within the
capsule-
production process.
Hard capsules containing gelatin are made by dipping 'gold' stainless steel
mold
pins at a temperature of 22 C in a 30-40% gelatin solution present at 50-60 C.
The pins
will pick up the target gelatin due to gelling while the excess runs off. The
viscosity of
the gelatin solution determines the quantity picked up by the molds during
capsule
formation. The pin bars are then rotated in order to facilitate spread of the
gelatin as
uniformly as possible over the subject mold surface. As before, the last step
is a drying
step.
Hard capsules containing MHPC are made on smaller mould pins to enable
capsules with thinner walls to be made. This is required to give them
sufficient strength
to be filled and retain the same external dimensions as a gelatin capsule. Two
methods
are used. One is using thermal gelation of HPMC. The other is using a gelling
agent (e.g.
carrageenan or gellan gum) and a gelation promoter.
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As the inventive modified CMC capsules do not exhibit the thermal gelation
behavior that MHPC or gelatin shows, typically a gelling agent should be
added. In case
of soft capsules this is required to form a wet sheet together with the
modified CMC, that
will be mechanically deformable. When applied as hard capsules the gelling
agent is
needed to get sufficient surface gelling at the mold pins thereby picking up
sufficient
modified CMC material to form the required (uniform) capsule dimension.
The gelling agent should not compromise the modified CMC film-forming
properties, nor cause too great a viscosity increase within the solution.
The final modified CMC-containing capsule films should have a suitable
strength.
Furthermore, the capsules should be readily soluble in biological fluids at
body
temperature.
An example where the modified CMC can be used to form capsules would be in
combination with gellan gum. The low acyl version of this product has a
setting
temperature of approximately 40 C (within the same range as gelatin). However,
the
gellan guin is much higher in gel strength than cominonly used gelatins and so
only a low
concentration can be used. Higher levels result in gellan gum-alone solutions
that are too
thick and viscous to be processed. Using the modified CMC in conjunction with
gellan
gum allows the CMC to function as a film former and the gellan gum to
thermally set aiid
form the capsule in a manner similar to the gelatin. Other gelling
hydrocolloids can
function in the same way with the only requirement being that they have an
easily
triggered gel mechanism. Those skilled in the art of hydrocolloids are
familiar with the
therinal gelation of xanthan and locust bean gums or with the calciuin
gelation
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mechanism of sodium alginate, and such possible alternatives are thus non-
limiting
examples of potential gelling hydrocolloids for this purpose. A wide range of
gelling
hydrocolloids can be used in conjunction with the modified CMC when it is
realized that
the film forming properties of the modified CMC can be effectively paired with
the gel
forming properties of the second hydrocolloid system. Thus, there exists a
wide range of
possibilities with respect to unique capsule formulations in combination with
the
inventive modified CMC materials.
Such approaches (using a gel forming system with some other material of low
viscosity) have been used before but these systems do not take advantage of
the film
forming properties of the modified CMC described in this invention. Since a
capsule is a
special case of film formation, the use of modified CMC of reduced molecular
weight
provides a significant improvement over capsules previously produced with
gelling
hydrocolloids in combination with simple "fillers" (such as maltodextrose). In
this
situation, then, this invention concerns, as one possible embodiment, the
instance
whereupon the non-gelling hydrocolloid serves an important role as a film
former for
capsule formation.
The processes followed for production of the inventive modified CMC materials
and films and/or capsules made therefrom are delineated below.
1. Modified CMC Production
Initially, samples of different CMC materials were modified to different
levels of
molecular weights in order to provide materials for ultimate film production.
In each
instance, the basic degradation method was preferably performed enzymatically
and
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followed the basic steps of: Tap water was charged to a barrel that was placed
in a water
bath of 50 C. From a food grade cellulase (Econase CE from AB enzymes) from
Trichodef=naa r eesei, 0.1-1% (weight percent on dry CMC basis) was added to
the water
(exhibiting a pH of 5.8 as adjusted by a 21 % phosphoric acid solution). While
stirring
thoroughly CMC from CPKelco (the different types are noted within Table 1,
below) was
slowly added over a period of an hour to a concentration of 20% in water. The
pH was
then adjusted again to 5.8 using the same phosphoric acid solution. The
reaction was
performed at 50 C while stirring for 16 hours and was eventually stopped by
inactivating
the enzyme in an autoclave at 121 C for one hour. The resultant modified CMC
solutions were then dried by either freeze-drying or spray drying.
Table 1
Characteristics of Modified CMCs
CMC starting material Mod CMC Mod CMC Enzyme
Ex. Tradename Deg of Subst. Mol. Weight Amt. (% b/w)
1 CEKOL 30000A 0.91 7200 1.0%
2 CEKOL 30000A 0.91 21800 0.1%
3 CEKOL 2000S 1.26 21200 1.0%
4 CEKOL 2000S 1.26 50500 0.1%
CEKOL 50000 0.60 28000 0.1%
6 CEKOL 30000 0.92 19600 0.1%
2. Solution Preparation (Hydrocolloid Dissolution Rate)
An important quality of films is how quickly they dissolve or disperse. To
compare the modified CMC with other hydrocolloids the solubility of
hydrocolloids was
compared. Solutions were prepared to a concentration that can be applied to
cast films
from without addition of plasticizer or other ingredients. The solutions were
prepared in
standardized tap water (1 g NaCI + 0.219 g CaC12.6H20 in 1 liter demineralised
water).
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With an IKA Viscoklick system attached to an upper stirrer the torque was
monitored. At
the time that a hydrocolloid is in solution, the torque becomes constant
(constant
viscosity). This time to constant torque is taken as solubility time. The
table shows the
hydrocolloid, the concentration of the solution prepared and solubility time.
The
concentration divided by the solubility time is a measure of how much
hydrocolloid can
be dissolved per time unit. This shows that the amount of modified CMC that
can be
dissolved per time unit is much higher than most other hydrocolloids, as well
as the total
amount of modified CMC that can be dissolved. Thus, it was believed that such
modified
CMC materials would provide excellent quick dissolve film components. It is
important
to note that although the Methocel E5 sample exhibits excellent dissolution
rates, films
prepared with such materials exhibit excessive adhesion characteristics and
thus, in
actuality, such films would exhibit much slower dissolution in practice than
modified
CMC films. As noted below, the modified CMC materials exhibited much better
low
adhesion properties and thus in practice provided much better quick
dissolution
capabilities than such hydroxypropylmethylcellulose materials.
Table 2 as follows shows comparatives results of solubility of modified CMC
and
other hydrocolloids:
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TABLE 2
Conaparisons of solubility of modified CMC with Other Hydrocolloids
Hydrocolloid Concentration of Solubility time Concentration /
solution % min solubility time
Example Number 2 from Table 1 40 9.5 4.21
Example Number 4 from Table 1 40 7.6 5.26
CMC (CPKelco, CekolO 30) 12 19.9 0.60
Pectin D slow set ZO 8 11.5 0.70
Pectin X-939-040 12.5 8.7 1.44
Radiated Ceko130 (27kGy) 20 9.1 2.20
Pullulan 25 12.1 2.07
Hydroxy propyl methyl cellulose (Fluka; 15 16.9 0.89
15 mPas, 2% water at 25 C
MethocelOO E5 (HPMC Dow Chemicals) 30 3.8 7.9
Methocel E50 (HPMC Dow Chemicals) 20 6.9 2.9
Keltrol0 (xanthan, CPKelco) 3 7.5 0.40
Thus, the modified CMC types exhibited excellent solubility times and a high
concentration of the modified CMC can be prepared as compared with the other
hydrocolloids tested.
3. Modified CMC Film Production
The modified CMC materials from Table 1, above, were then utilized to form
films in accordance with the following method: The modified CMC was weighed
out
and dissolved into tap water. After the modified CMC was dissolved completely,
glycerol was weighed out and added to the dissolved modified CMC solution,
(prefeiTed;
could be premix, too) Air bubbles within the resultant solution were removed
by
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centrifugation or by vacuum. That solution was then cast using a draw-down bar
on a
plastic sheet into thin even layers. The layers were then dried at room
temperature to
form films exhibiting final thicknesses of between 20 and 500 m. Table 3,
below, tlius
indicates the different films produced with the plasticizer (i.e., glycerol)
to modified
CMC ratio. Note that the remainder of the solution utilized to form the films
was tap
water (thus, if 50% was CMC, and the plasticizer:CMC ratio is 1:10, then 5% of
the
solution was plasticizer, and 45% was then tap water, for example). Also, if
no
plasticizer was added, the term "None" is used and thus the remainder of the
film-
producing solution was tap water alone. Additionally, film example 18 included
6%
(ratio CMC: modified CMC - 1: 6) of non-modified CMC (CEKOL 30) in
combination
with the noted modified type, and thus the amount of tap water was adjusted
accordingly.
Furthermore, film example 23 included 1% of pectin GENU X-934-04) in
combination
with the noted modified type, with 22.8 g of water. Lastly, the notation of G
after the
plasticizer:CMC ratio denotes glycerol as the plasticizer, whereas the
notation of S
denotes the utilization of sorbitol.
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TABLE 3
FilTras Pf oduced from Modified CMC Materials
Film Ex. # CMC Ex. # from Table 1(%) Plasticizer: CMC Ratio Thickness (mm)
1 1(50%) 1:10 G 0.087
2 2(35%) 1:10G 0.088
3 1(45%) 1:3 G 0.057
4 2(35%) 1:3 G 0.081
2(35%) None 0.076
6 3 (38.7%) None 0.081
7 3(40%) 1:10 G 0.032
8 3(40%) 1:10 G 0.143
9 3(40%) 1:10 G 0.341
4(40%) 1:10 G 0.061
11 4(40%): 1:10G 0.195
12 4(40%) 1:10 G 0.454
13 2(40%) 1:10 G 0.032
14 2(40%) 1:10 G 0.080
2(40%) 1:10 G 0.144
16 2(40%) 1:10G 0.459
17 2(40%) 1:10 S 0.094
18 6(35%) None 0.086
19 6(35%) None 0.068
4(35%) 1:10 G 0.088
21 3(38.7%) 1:10 G 0.073
22 3(40%) 1:10 S 0.070
23 1(40%) 1:3 G 0.087
These resultant films were then analyzed for various physical characteristics
as
noted below. Note that not all of the films produced within the Table 3 above
were
analysed using each method below.
4. Analysis of Films
i) Flexibility
Film Examples 1-4 from Table 3 were tested for flexibility. The films produced
thereby were bent baclcward length-wise (hairpin bending) to investigate the
breaking
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point thereof. If the film exhibiting cracking when bent in such a fashion, it
was
considered a failure. Film Example numbers 2-4 exhibited no cracking. Film
Example 1
exhibited greater brittleness. Film Examples 3 and 4 exhibited greater
flexibility overall,
but due to the high plasticizer content the films are tacky. Thus, in terms of
molecular
weight, at least, the higher the molecular weight, coupled with lower amounts
of
plasticizer provided excellent flexibility results without tackiness.
Additionally, the degree of substitution was considered as a potential
influence on
the flexibility of the inventive films. Film Example nuinbers 5 and 6 were
thus tested for
cracks after drying and the ability to hairpin bend as above. Film Example 6
was the
better of the two, with Film Example number 5 exhibiting some cracking. It is
evident
from the results that a higher DS permits creation of a film of greater
flexibility.
Lastly, Film Example numbers 18 and 19 (18 again including non-modified
CMC) were tested for flexibility. Number 18 was better in terms of low
cracking, but
number 19 was effective to a lesser degree in bending.
ii) Film Dissolution
Films were cut into pieces and placed into dia frames (24 X 36 mm). The dia
frames, containing the films, were placed into a water bath exhibiting a
temperature of 37
C. The water was gently stirred and dissolution time of the films was measured
in terms
of monitoring by visual observation. The following Table 4 shows dissolution
times
(average of two separate measurements) and takes into account differences in
molecular
weight, degree of substitution, and film thickness as factors in film
dissolution for
inventive modified CMC films.
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TABLE 4
Ihafluence of DS and Mw on dissolution time of modified CMC films
Film. Example Number Thickness DS Mw Dissolution
(mm) (Dalton) time
(sec)
7 0.032 1.26 21,200 1
8 0.143 1.26 21,200 10
9 0.341 1.26 21,200 54
0.061 1.26 50,500 12
11 0.195 1.26 50,500 38
12 0.454 1.26 50,500 114
13 0.032 0.91 21,800 2
14 0.080 0.91 21,800 6
0.144 0.91 21,800 14
16 0.459 0.91 21,800 126
The results show that dissolution rate increases clearly as the thickness of
the
films increase, an increase in molecular weight results in an increase in
dissolution time,
and a lower DS results in an increase in dissolution time. Thus, it was
determined that all
three factors accord some degree of influence on the film dissolution rate.
Lastly, further comparisons between modified CMC films and typical
hydrocolloids used for making films were made as well. The following Table 5
provides
those measurements. The thickness of the films is also included in the table,
because
thickness has a clear influence (thicker films result in longer dissolution
time). The
results clearly show that pullulan and the hydroxypropyl methyl cellulose
films dissolve
much slower than the modified CMC saniples. A remark on pullulan needs to be
made in
that a film with only pullulan as a liydrocolloid adlieres to the sheet that
it has been cast
on. Such a film with regular film thickness cannot be removed from the sheet.
The
pectin films also dissolve slower than the modified CMC films, especially when
film
thiclazess is taken into account.
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TABLE 5
Dissolution times of nzodified CMC filnas conzpared to other hydrocolloids
Hydrocolloid Plasticizer ratio Thickness Dissolution time
h drocolloid/ 1 cerol (mm) sec
Example # 4 from Table 1; 10:1 0.061 12
DS 1.26; Mw 50,500
Example # 2 from Table l; 10:1 0.080 6
DS 0.91; Mw 21,800
CMC (CPKelco, Cekol 30) 10:1 0.046 9
Radiated CMC [radiated Cekol 30 10:1 0.096 40
(27kGy)]
Pectin (CPKelco X-939-040 10:1 0.023 14
Pectin D Slow set-ZO (CPKelco) 10:1 0.018 14
Hydroxypropyl methyl cellulose 10:1 0.050 26
(Fluka; 15 mPas, 2% water at 25
0c
Methocel E5 (HPMC Dow 10:1 0.080 50
Chemicals)
Methocel E50 (HPMC Dow 10:1 0.080 70
Chemicals)
Pullulan 10:1 0.256 84
Thus, the modified CMC films measured provide excellent dissolution in
comparison with all of these standard types.
iii) Mechanical Properties
Certain properties, such as tensile strength, elongation, toughness, and
elastic
modulus were measured for resultant films as well to indicate the viability of
such films
as potential commercial products. Such measurements were taken through
standard
techniques. A texture analyzer from Stable Micro Systems equipped with tensile
grips
was used to determine the znechanical properties of the films at 50% RH. To
determine
the influence of molecular weight, Film Exainple numbers 20 and 21 were
analysed for
such mechanical properties. Film Example 20 has a higher molecular weight than
Film
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Example 21 (MW of 50500 versus 21200). The average of 6 measurements was
calculated and shown in table 6.
Table 6
fiaf uence molecular= weight of 7nodified CMC on mechanical properties of
filrns
Film 20 Film 21
Tensile Stren h/mm 29.4 13.6
Elongation (%) 6.6 5.2
Toughness (N/mm *% 144.5 50
E-modulus (N/min /%) 11.7 6.3
The toughness of Film 20 is almost 3 times as high as Film 21, while the
elongation of film 20 is only 1.3 lo bigger than the elongation for film 21.
The E-modulus
and the tensile strength of Film 20 is about twice as high as for Film 21.
iv) Clarity and Haziness
Films prepared from modified CMC have a high clarity and low haziness. This is
already visible when the solutions are prepared. Modified CMC was compared to
other
hydrocolloids used for making films. The clarity and haziness were measured
with a
BYK-Gardner haze-gard plus of 10 % solutions of hydrocolloids. If the DS of
the
modified CMC is not too low the clarity is high and the haziness is low. Other
hydrocolloids may have a high clarity, but they can have a high haziness like
the pectin
samples. The results are shown in the table below. Each sample solution
mentioned
below was measured at the same thickness (2 mm).
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TABLE 7
Clarity and haziness of hydrocolloids solutions
Hydrocolloid Clarity Haze
Example # 5 from Table 1; Mw 28000; DS 0.60 31.1 60.5
Example # 2 from Table 1; Mw 21800; DS 0.91 96.0 6.26
Example # 4 from Table 1; Mw 50500; DS 1.26 95.3 10.2
CMC (CPKelco, Cekol 30) 76.5 15.5
Radiated CMC (radiated Cekol 30 (27kGy)) 90.4 7.42
Pectin (CPKelco X-939-04) 95.1 93.4
Pectin D Slow set-Z (CPKelco) 90.9 89.1
Pullulan 98.5 20.8
Hydroxypropyl methyl cellulose (Fluka; 15 mPas, 2%
water at 25 C 98=7 1.94
Hence, the modified CMC films, having not too low DS levels, exhibited
excellent measurements in both properties as opposed to the comparatives (MHPC
is an
exception).
v) Plasticizer Modifications
Other plasticizers than glycerol can be used to prepare films from modified
CMC.
Film Example numbers 17 and 22 prepared with sorbitol as a plasticizer
resulted both in
flexible and not tacky films tested in humidity range from 20% up to 70%
relative
humidity (RH).
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5. Films with Additives
i)Confectionary Film
Formulation Percent
Modified CMC (exam le # 2) 34
Deionized Water 54.5
Glycerol (99.0%) 1
Orange Flavor (McCormick Juice type n/a
OS) 6
Citric Acid 2
Malic Acid 2
Sucralose, micronized (S lenda Brand) 0.5
Red # 40 FD&C (10% Solution) T.S.
Yellow #5 FD&C (1% Solution) T.S.
Total 100
Such a film was produced in accordance with the composition of the preceding
table through the following process: Modified CMC was added to the water and
glycerin
while mixing at 1200 rpm with a propeller mixer. After addition of the
modified CMC
the mixing was continued at high speed. After -15 minutes the sucralose was
added.
Addition of citric and malic acid was started when the sucralose had fully
dispersed.
After all the acid was added first the flavor was added and then the color.
When the
sample was uniform in appearance, the mixer was removed and the sample was
deaerated
using either vacuum or centrifugation. A portion of the solution was poured on
to the
plastic sheet and a draw down bar was used to draw the solution down into a
thin layer
resulting in a film of a thickness of about 0.05 mm. The films were then
allowed to stand
undisturbed until thoroughly dried. The resultant films exhibited excellent
dissolution
times (on par with those presented above) and tllus effective delivery of
flavoring.
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ii) Surfactant Film
Formulation Percent
Modified CMC example # 2 30
Deionized Water 49
Glycerol (99.0%) 1
Sodium Lauryl Sulfate (SLS) 20
Fragrance T.S.
Color T.S.
Total 100
Such a film was produced in accordance with the composition of the preceding
table and in accordance with the following method: Modified CMC was added to
the
water and glycerin while mixing at 1200 rpm with a propeller mixer. After
addition of
the modified CMC the mixing was continued at high speed. After -15 minutes the
remaining ingredients were added and when the sample was uniform in appearance
the
mixer was removed and the sainple was deaerated using either vacuum or
centrifugation.
A portion of the solution was poured on to the plastic sheet and a draw down
bar was
used to draw the solution down into a thin layer of a thickness of about 0.01
inch. The
films were allowed to stand undisturbed until thoroughly dried. Final film
thickness was
0.002 inch. The resultant films exliibited excellent dissolution times (on
par, again, with
those presented above) and surfactant delivery capability.
While the invention will be described and disclosed in connection with certain
preferred embodiments and practices, it is in no way intended to limit the
invention to
those specific embodiments, rather it is intended to cover equivalent
structures structural
equivalents aiid all alternative embodiments and modifications as may be
defined by the
scope of the appended claims and equivalence tla.ereto.
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