U.S. patent application number 10/306649 was filed with the patent office on 2003-07-10 for edible mcc/pga coating composition.
Invention is credited to Augello, Michael, Bliefernich, Eric H., Dell, Sheila M..
Application Number | 20030129238 10/306649 |
Document ID | / |
Family ID | 27558517 |
Filed Date | 2003-07-10 |
United States Patent
Application |
20030129238 |
Kind Code |
A1 |
Augello, Michael ; et
al. |
July 10, 2003 |
Edible MCC/PGA coating composition
Abstract
An edible, hardenable coating composition is disclosed
containing microcrystalline cellulose, a film forming amount of
propylene glycol alginate, and a strengthening polymer, optionally
in combination with at least one of a plasticizer, a surfactant, or
a filler. The coating composition of the present invention may be
applied to pharmaceutical and veterinary solid dosage forms,
confectionery, seeds, animal feed, fertilizers, pesticide tablets,
and foods and provides an elegant prompt release coating which-does
not retard the release of active ingredients from the coated
substrate.
Inventors: |
Augello, Michael; (Malboro,
NJ) ; Dell, Sheila M.; (New Hope, PA) ;
Bliefernich, Eric H.; (Yardville, NJ) |
Correspondence
Address: |
WOODCOCK WASHBURN LLP
ONE LIBERTY PLACE, 46TH FLOOR
1650 MARKET STREET
PHILADELPHIA
PA
19103
US
|
Family ID: |
27558517 |
Appl. No.: |
10/306649 |
Filed: |
November 27, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10306649 |
Nov 27, 2002 |
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09696780 |
Oct 26, 2000 |
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6500462 |
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60162514 |
Oct 29, 1999 |
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60167207 |
Nov 24, 1999 |
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60172526 |
Dec 17, 1999 |
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60189588 |
Mar 15, 2000 |
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60217499 |
Jul 11, 2000 |
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Current U.S.
Class: |
424/480 |
Current CPC
Class: |
A61K 9/286 20130101;
A61K 9/2853 20130101; A61K 9/2866 20130101; A61K 9/284
20130101 |
Class at
Publication: |
424/480 |
International
Class: |
A61K 009/36 |
Claims
What is claimed is:
1. An edible, hardenable, prompt release coating composition
comprising (a) microcrystalline cellulose, (b) a film forming
amount of propylene glycol alginate, (c) a strengthening polymer
and optionally (d) at least one of a plasticizer, a surface active
agent and a filler.
2. The coating composition of claim 1, comprising 5% to 50% by
weight microcrystalline cellulose, 10% to 50% by weight propylene
glycol alginate, and 5% to 25% by weight strengthening polymer.
3. The coating composition of claim 2, comprising 12% to 50% by
weight propylene glycol alginate.
4. The coating composition of claim 1 in which the strengthening
polymer is hydroxyethylcellulose.
5. The coating composition of claim 4, further comprising from 20%
to 30% by weight plasticizer.
6. The coating composition of claim 5, in which the plasticizer is
triacetin.
7. The coating composition of claim 4, further comprising from 1%
to 5% by weight surface active agent.
8. The coating composition of claim 4, further comprising from 10%
to 30% by weight of a filler.
9. The coating composition of claim 8, in which the filler is at
least one of mannitol or maltodextrin.
10. The coating composition of claim 1, in which the weight ratio
of microcrystalline cellulose to propylene glycol alginate is in
the range of 90:10 to 20:80.
11. The coating composition of claim 1, wherein the
microcrystalline cellulose has an average particle size in the
range of 1 to 50 microns.
12. The coating composition of claim 10, further comprising
carrageenan in an amount of from 3% to 20% by dry weight of the
composition.
13. The coating composition of claim 12, wherein carrageenan is
present in an amount in the range of 3% to 8% by dry weight of the
composition and the weight ratio of propylene glycol alginate to
carrageenan is in the range of 2:1 to 10:1
14. The composition of claim 12 wherein carrageenan is present in
an amount in the range of 9% to 20% by dry weight of the
composition and the weight ratio of propylene glycol alginate to
carrageenan is in the range of 2:1 to 0.8:1.
15. The coating composition of claim 1, wherein said composition is
a dry blend.
16. The coating composition of claim 1, wherein said composition is
an aqueous dispersion.
17. The coating composition of claim 1 further comprising a
coloring agent.
18. A solid dosage form coated with the composition of claim 1.
19. A method for forming an edible, hardenable, prompt release
coating composition comprising i) combining (a) microcrystalline
cellulose, (b) a film forming amount of propylene glycol alginate,
(c) a strengthening polymer and optionally (d) at least one of a
plasticizer, a surface active agent and a filler; and ii) forming a
film coating by spraying an aqueous suspension of i) onto a
substrate.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit of prior Provisional
Application Nos. 60/162,514, filed Oct. 29, 1999, 60/167,407, filed
Nov. 24, 1999, 60/172,526, filed Dec. 17, 1999, 60/189,588, filed
Mar. 15, 2000, and 60/217,499, filed Jul. 11, 2000.
FIELD OF THE INVENTION
[0002] This invention relates to edible, hardenable coating
compositions comprising microcrystalline cellulose (MCC), a film
forming amount of propylene glycol alginate (PGA) and a
strengthening polymer, optionally containing a plasticizer, a
surface active agent, a filler, a coloring agent or a combination
of such optional ingredients. The coatings of the present invention
can be applied to pharmaceutical, including neutraceutical, and
veterinary solid dosage forms, such solid substrates such as seeds,
animal feed, fertilizers, pesticide tablets and granules, and also
to confectionery and foods. They are readily dispersed in aqueous
media, and, when applied as a coating, provide high lustre
coatings, which do not retard or extend release of active
ingredient from a coated substrate.
BACKGROUND OF THE INVENTION
[0003] It is a common practice to coat pharmaceutical and
veterinary tablets to obtain several advantages. Among these are to
improve the surface characteristics of tablets to make them easier
to swallow, to reduce the absorption of water or moisture which can
potentially degrade the active ingredient or promote some other
undesirable change in the tablet structure, and simply to make a
more elegant appearing tablet.
[0004] Another very important function of a pharmaceutical or
veterinary tablet coating is to improve the integrity of the tablet
itself. Uncoated tablets are often subject to being abraded or
chipped, causing a loss of active ingredient in the process. More
dramatically, they may break into two or more pieces. One measure
of a useful coating is its ability to prevent any of these physical
degradations of tablet structure. The effectiveness of a coating
material to prevent abrading, chipping, or breakage of the tablet
is determined by friability testing.
[0005] Confectionery and foods may be coated with a formulation to
preserve the confection or food from deteriorating by contact with
the oxygen and the moisture in the atmosphere. Coatings also can
provide improved appearance and desirable organoleptic properties
to the food as well as preventing loss of flavor.
[0006] Seeds may be coated to preserve the viability of the seeds
by protecting against moisture. They may also be coated as a means
for increasing particle size to facilitate mechanical planting. A
dye can be included in the coating formulation to identify the
seeds as to quality, type, or some other designation. Frequently, a
pesticide, e.g., a fungicide, is incorporated into the coating
formulation to protect both the seed itself and the seedling that
results from germination of the seed. In all cases, this coating
must not decrease the viability of the seeds or interfere with
germination when the seeds are planted in the soil.
[0007] Animal feed may be coated to improve its flowability,
appearance and its resistance to powdering or dusting. In such
applications, the coating may be formulated to include vitamins,
hormones, antibiotics, or the like, to benefit the livestock which
will consume the feed.
[0008] Fertilizers, in either granular or tableted forms, may be
coated to retain the integrity of the form and, especially, to
protect the fertilizer from moisture which can cause agglomeration
during storage, which could make rapid, even application to the
soil difficult or inconvenient.
[0009] Coating of tableted pesticide formulations serves to
maintain the integrity of the tablets or granules until they are
placed in water where they rapidly disintegrate, forming a solution
or slurry to be applied to the soil or plants. A second, and
equally important, function of the coatings on tablets containing
pesticides is to prevent human contact with the pesticide, thereby
increasing safety for those handling and applying the
pesticide.
[0010] In the preparation of a coating formulation to be sprayed,
the film-former is usually dissolved or dispersed in a solvent, for
example, water, along with the other ingredients of the
formulation. In aqueous systems, since many polymers require
significant time to become fully hydrated, the coating formulation
must frequently be prepared in advance of the time it is to be
applied to the tablets. A common procedure is to prepare these
coating formulations the day preceding the coating operation in
order to assure adequate hydration of the polymers used in
them.
[0011] A particular disadvantage of coatings based primarily on
hydroxypropylmethylcellulose (HPMC) is that the coating may harden
over time and therefore increase tablet disintegration times. An
increase in disintegration time delays the bioavailability of the
active ingredient at least in proportion to the increase in
disintegration time. Many other agents commonly used in coating
compositions are also known to delay release of pharmaceutical
agents, such as enteric coatings which use polymeric film forming
materials which are insoluble in water, or gastric fluid, some of
these being specifically selected to by-pass both the stomach and
small intestine and provide colonic release.
[0012] The coatings of this invention meet U.S. Pharmacopeia
standards for rapid or immediate dissolution (U.S.P. monograph 23)
of active ingredients from tablets or other solid dosage forms
coated with them. They provide prompt release or dissolution
consistent with the release rates which is normally obtained with
the uncoated tablets or other substrates. Thus, they do not
adversely impact or retard release of active ingredients from a
substrate coated with them. Further, the coatings of this invention
are readily dispersed and rapidly hydrated in aqueous media for
application to a coating substrate, and provide elegant coatings
which have all the benefits of coatings now in commercial use
without the drawbacks that are common to them.
SUMMARY OF THE INVENTION
[0013] It has been found that these and other advantages may be
achieved in accordance with the present invention by a coating
composition which comprises a unique combination of materials
specifically adapted for prompt release when placed in aqueous
media or ingested. The coating composition of the present invention
comprises microcrystalline cellulose, a film forming amount of
propylene glycol alginate and a strengthening polymer, and may
additionally contain a plasticizer, a surface active agent, a
filler, a coloring agent or combination of these additional
ingredients. More specifically, the present invention provides a
prompt release, edible, hardenable coating composition, as well as
dry coatings and aqueous dispersions thereof and solid dosage forms
coated therewith.
DETAILED DESCRIPTION OF THE INVENTION
[0014] For purposes of this application, the term "edible" is
intended to mean food grade materials which are approved by
regulatory authorities for use in pharmaceutical or food
applications. The term "hardenable," used to describe the coating
compositions of this invention, is intended to include only those
coating compositions that are capable of being dried from an
aqueous solution or dispersion thereof into a solid coating which
resists abrasive forces, i.e. a hardened coating, as distinguished
from those "enrobing" coatings on confections which set up into a
soft coating that can be handled and packaged but which do not
resist abrasive forces significantly. The terms "immediate,"
"rapid," or "prompt," as applied to dissolution rates or times for
the coating compositions of this invention or tablets coated with
the compositions of this invention, mean that the coatings of this
invention meet U.S. Pharmacopeia standards (U.S.P. monograph 23)
for rapid or immediate dissolution of active ingredients from
tablets or other solid dosage forms coated with them. Thus, they
provide prompt release or dissolution consistent with the release
rates which is normally obtained with the uncoated tablets or other
substrate. They do not, when placed in water or ingested, adversely
impact or retard release or dissolution of tablets or other dosage
forms coated with them. Coatings made in accordance with the
present invention are substantially or completely disintegrated
and/or dissolved within less than 10 minutes after being ingested
or placed in aqueous media. These definitions are intended to apply
throughout this application unless a contrary meaning is clearly
indicated.
[0015] The microcrystalline cellulose, simply blended with
propylene glycol alginate, provides important film characteristics
required to provide an elegant coating which is particularly useful
in, for example, coating pharmaceutical and veterinary tablets,
caplets, granules, and spheres which contain active ingredients
which require release promptly after being placed in aqueous media
or ingested.
[0016] Microcrystalline cellulose is a purified, partially
depolymerized cellulose that is generally produced by treating a
source of cellulose, preferably alpha cellulose in the form of a
pulp from fibrous plants, with a mineral acid, preferably
hydrochloric acid. The acid selectively attacks the less ordered
regions of the cellulose polymer chain, thereby exposing and
freeing the crystallite sites, forming the crystallite aggregates
which constitute microcrystalline cellulose. These are then
separated from the reaction mixture and washed to remove degraded
by-products. The resulting wet mass, generally containing 40 to
60
[0017] For purposes of this invention, a film forming amount of
propylene glycol alginate may be in the range of about 10% to about
50%, more specifically about 12% to about 50%, by dry weight of the
coating composition. The propylene glycol alginate employed in the
present invention may vary widely in viscosity. A typical high
viscosity propylene glycol alginate is such that a 2% aqueous
solution thereof has a viscosity in the range of 700 to 1800
mPa.multidot.s at 25.degree. C., and is commercially available as
Protonalg ester SD-LB, Pronova/FMC Corporation. A typical low
viscosity propylene glycol alginate is such that a 2% aqueous
solution thereof has a viscosity in the range of 20-30
mPs.multidot.s at 25.degree. C., and is commercially available as
Profoam.RTM., Pronova/FMC Corporation.
[0018] High viscosity propylene glycol alginate is generally
employed in a lower amount than that employed for low viscosity
material, typically in the range of 10% to about 20% by dry weight
of the coating composition, as illustrated in examples 1-6 below.
Use of substantially higher amounts of high viscosity propylene
glycol alginate may result in coating solutions which are too
viscous, tend to plug coating equipment, and may not flow
sufficiently to form a satisfactory coating. Low viscosity
propylene glycol alginate conversely is generally used in a higher
amount, typically in the range of 20% to 50% by dry weight of the
coating composition, as illustrated in examples 7 through 30.
[0019] Propylene glycol alginate may be used in combination with
other film forming materials, for example, carrageenan and
cellulosic polymers such as HPMC and hydroxypropylcellulose.
[0020] Carrageenan, preferably iota carrageenan, may suitably be
employed as a multifunctional component in combination with
propylene glycol alginate at a concentration in the range of about
3% to about 20% of the dry weight of the coating composition. When
carrageenan is employed in the composition at a concentration in
the range of about 3% to about 8%, it is believed to serve
primarily to improve the gloss of the resulting coating, that is,
as a gloss enhancer. When used for this purpose the weight ratio of
propylene glycol alginate to carrageenan is suitably in the range
of about 2:1 to about 10:1.
[0021] Carrageenan may also be used at a level above about 9%, for
example, at a concentration in the range of about 9% to about 20%,
more specifically in the range of 10% to about 15%. At these levels
it is believed to serve not only to improve gloss of the coating,
but also to contribute film forming properties and to contribute to
the strength and integrity of the resulting film coating. Depending
on the weight ratio of propylene glycol alginate to carrageenan,
carrageenan may be viewed to function as a co-film-former or as a
supplemental or secondary film-former in the coating compositions.
Such a weight ratio of propylene glycol alginate to carrageenan may
be in the range of 2:1 to about 0.8:1. For example, when the weight
ratio of propylene glycol alginate to carrageenan is in the range
of about 1.5:1 to about 2:1, propylene glycol alginate may be
considered to be the primary film-former and carrageenan the
secondary film-former, as illustrated in examples 18 through 21 and
25 through 30. When approximately equal amounts of propylene glycol
alginate and carrageenan are employed, that is, when the propylene
glycol alginate to carrageenan weight ratio is, for example, in the
range of about 1:0.8 to about 1:1.2, each of them may be considered
to contribute relatively equal film forming properties to the
resulting film coating, thus are considered to be co-film-formers
as illustrated by examples 18 and 20-24.
[0022] The weight ratio of microcrystalline cellulose to propylene
glycol alginate in the compositions of this invention may vary
depending on the application, but generally range from about 90:10
to about 20:80, more specifically from about 80:20 to about 20:80.
A particular advantage for the dry, physical blends is that the
ratio can be easily changed by simple blending techniques rather
than manufacturing different ratios of a coprocessed material.
Thus, the dry, physical blends provide great flexibility for
specific applications having different requirements.
[0023] A dry, physical blend of microcrystalline cellulose and a
film forming amount of propylene glycol alginate, a strengthening
polymer, preferably, hydroxyethylcellulose (HEC), are present in
the coating formulation of this invention, advantageously in
combination with other optional ingredients such as a plasticizer,
a surfactant, a filler or a coloring agent, other conventional
excipients or combinations thereof. Other strengthening polymers
which can provide the same benefit and may be used instead of HEC
include HPMC, hydroxypropylcellulose, ethylcellulose,
methylcellulose and polyvinylpyrrolidone (PVP), however care must
be exercised in the use of such alternative materials to avoid
retarding release of active ingredients and/or bioavailability.
[0024] The preferred amount of strengthening polymer is less than
the total amount of microcrystalline cellulose and propylene glycol
alginate present in the composition. Depending on the desired
hardness of the coating, the strengthening polymer may be employed
in the composition at a level of about 0.5% to about 30%,
advantageously about 5% to 30% to provide strength and improved
appearance to the coating. This strength can be demonstrated by
casting films of coating formulations on a flat, non-adherent
surface, cutting strips of uniform width from the casting, and
subjecting the strips to tensile testing on, for example, an
Instron Tensile Tester. The results of these tests show a very
significant increase in tensile strength and decreased brittleness
of the film when HEC or another strengthening polymer is included
in the formulation. Strengthening polymers suitable for use in this
invention, which will not retard release from tablets or other
solid dosage forms, are those polymers having a viscosity equal to
or less than 20 mPa.multidot.s in a 2% aqueous solution at
20.degree. C. When a strengthening polymer is employed in the
composition in absence of a plasticizer, it is generally employed
at about 15% to about 30% by dry weight coating composition, and
HEC is preferably employed at about 20% to about 25% by dry weight
of the formulation.
[0025] In addition to the foregoing ingredients, the compositions
of this invention may also contain at least one of a plasticizer, a
surfactant, a filler, a coloring agent or a combination of these
additional components of the composition. Thus, a conventional
plasticizer may also be included in the coating composition.
Suitable plasticizers include polyethylene glycol, triacetin,
dibutyl sebacate, propylene glycol, sorbitol, glycerin, and
triethyl citrate. Of these, triacetin is preferred. These
plasticizers may be employed in the coating compositions of the
invention at about 18% to about 36% by dry weight of the coating
composition, advantageously about 20% to about 30% by dry weight of
the coating composition.
[0026] Fillers suitable for use in the compositions of the
invention include, for example, calcium carbonate, dicalcium
phosphate and carbohydrates, such as starch, maltodextrin, lactose,
mannitol and other sugars or croscarmellose sodium. Of these,
mannitol or maltodextrin is a preferred filler. Surfactants which
are either anionic or nonionic may be used beneficially in the
edible, hardenable coating compositions of the present invention.
Useful surfactants may be, for example, sodium lauryl sulfate,
hydroxylated soy lecithin, polysorbates, and block copolymers of
propylene oxide and ethylene oxide. Coloring agents and opacifiers
which may be used in these coatings or added to a suspension
thereof include aluminum lakes, insoluble pigments, water soluble
dyes, titanium dioxide, and talc. Stearic acid or a salt or ester
thereof, may be included at a level of about 1% to about 5% by dry
weight of the compositions to increase gloss of the coating,
particularly when a plasticizer is not employed in the
composition.
[0027] A coating formulation of this invention may be sold as a dry
powder formulation or as a ready-to-use dispersion in water. For
aqueous dispersions it is preferred that these be prepared under
aseptic conditions. Heating the water to an elevated temperature,
for example, 85.degree. C., prior to preparation of the dispersion
has shown that bacteria, mold, and yeast growth are prevented for
at least 48 hours on agar pour plates. Therefore, if the containers
for the dispersion are properly sanitized and then kept closed
after being filled until the dispersion is used, there is little
likelihood of bacteria, mold, or yeast growing in the dispersion.
Alternatively, if a formulation is to be sold as an aqueous
dispersion to be stored for a period of time, a preservative may be
added. A combination of methyl and/or propyl paraben has been found
to be useful in this regard.
[0028] On a dry weight percentage basis the composition of this
invention comprises from about 15% to about 50% of microcrystalline
cellulose, about 10% to about 50% by weight of propylene glycol
alginate, and about 5% to about 25% of strengthening polymer. If a
plasticizer is employed, it is advantageously used at about 20% to
about 30% by weight of the composition. The composition of the
invention may also include an inert filler at about 2% to about 28%
by weight. Optionally, about 1% to about 30% by weight of the
formulation may comprise edible coloring agents and opacificiers
such as talc or titanium dioxide, including from 1% to about 8% of
coloring component such as a food dye or pigment, preferably about
1% to about 3%. Other optional ingredients may include a surfactant
at about 0.5% to about 10%, advantageously 0.5 to about 7%,
preferably 1.25% to 3% when a filler such as mannitol is present.
When no filler is employed higher amounts of surfactants such as
lecithin may be employed at a level of about 3% to about 20%.
Preservatives, such as methyl paraben at 0.75% to 1.50% and/or
propyl paraben at 0.075% to 0.15% may also be present in the
formulation.
[0029] The low level of fillers present in these coating
formulations, particularly when the opacifier is titanium dioxide,
enables the formulator to utilize relatively small amounts of
coloring agent. Since coloring agents are quite costly, this
provides a significant cost reduction from those formulation
requiring from 6% to about 16% to effectively color prior art
coating formulations.
[0030] The viscosity of the hydrated formulation can be important.
It ideally should be low enough to be pumped to a spray unit
continuously and then sprayed evenly in a useful pattern onto the
substrate being coated. A useful concentration of the dry
ingredients in water on a weight percentage basis, therefore, may
be about 6% to about 15%, advantageously 6.5% to 11%, preferably
about 8% to about 11%. To assure uniformity of the coating
composition, it may be preferable to maintain agitation of the
aqueous dispersion during the entire period of its being sprayed
onto the pharmaceutical or veterinary solid dosage forms,
confectionery, seeds, animal feed, fertilizer, pesticide tablets,
or food.
[0031] The preferred edible, hardenable, prompt release coating
formulations of this invention may generally be prepared and used
according to a simple procedure. A dry blend of microcrystalline
cellulose and propylene glycol alginate, and a strengthening
polymer, such as hydroxyethylcellulose, and optionally at least one
additional ingredient, such as polyethylene glycol or other
acceptable plasticizer, optionally together with a solid filler
such as maltodextrin, lactose, mannitol or the like, preservatives,
and/or surfactants are blended to form dry coating composition.
Addition of edible coloring agents, for example, a water soluble
dye or a pigment, may precede the hydration step required to
prepare the final coating formulation. This dry mixture is then
added slowly to the vortex of stirred, purified water. Stirring of
this mixture is continued for a sufficient period to allow all of
the components to be fully hydrated. If a colored coating material
is required a water soluble dye or a pigment may also be added,
preferably as a dispersion or solution, to the hydrated coating
composition. Optionally surfactants, and/or plasticizers may also
be added at this stage of the process.
[0032] In the formulations of microcrystalline cellulose and
propylene glycol alginate, a simple propeller mixer provides
adequate agitation for rapid hydration. The period of hydration may
be as short as 0.5 hours. It may, and preferably should, be longer,
but more than 3 hours is not believed to be necessary. Hydration
can take place at room temperature or at elevated temperatures as
high as 65.5.degree. C. (150.degree. F.), preferably at a
temperature about 48.9.degree. C. (120.degree. F.). The time
required for full hydration and the viscosity of the dispersion are
both considerably reduced when the dispersion is prepared at an
elevated temperature, but coating dispersions prepared at ambient
temperature only require an increase in hydration time and a slight
reduction in solids content to perform completely satisfactorily.
As previously stated, these formulations may be prepared on the day
preceding the coating operation, if that is more convenient;
however, a period of mixing will be required to overcome the
thixotropic behavior of a formulation which sets up during
overnight storage. Unlike coating formulations based primarily on
hydroxyalkyl ethers of cellulose, for example, HPMC, constant
stirring of the microcrystalline and propylene glycol
alginate-based formulations of this invention does not need to be
continued throughout the coating procedure, but mixing may
continue, if preferred.
[0033] Any commercial spray coater may be used to apply the
coating. Examples of useful coaters are Vector High Coaters
manufactured by Vector Corporation and Accela-Cota manufactured by
Thomas Engineering. Equipment variables which one skilled in the
art can manipulate to provide an elegant coating based on dry
blends of microcrystalline cellulose and propylene glycol alginate,
include inlet temperature, outlet temperature, air flow, speed of
rotation of the coating pan, and the rate at which the coating
formulation is pumped to the coater. It is important that the inlet
and outlet temperatures be controlled so that they are high enough
to efficiently dry the coating to prevent the tumbling action of
the already-coated tablets from damaging the newly-applied coating
before more coating is applied to the same tablets.
[0034] Hydroxyethylcellulose binds water more effectively than
propylene glycol alginate does. Thus, the presence of the major
amount propylene glycol alginate in the formulations of this
invention has a significant effect on the speed of drying of the
edible coatings. Drying times are reduced considerably because of
the presence of the propylene glycol alginate which dilutes the
negative effect of HEC on drying time. Thus, in the case of low
melting active pharmaceutical agents, for example, ibuprofen, the
outlet temperature can be reduced and still provide short enough
drying time to be commercially useful.
[0035] Hydroxyethylcellulose is particularly susceptible to
clogging spray nozzles at high temperatures. An additional benefit
provided by the formulations of this invention is the avoidance of
clogging of the spray nozzles with dispersions being sprayed at
high temperatures.
[0036] The level of coating applied to pharmaceutical or veterinary
dosage forms is preferably between about 0.5% to about 4% by weight
of the uncoated dosage form, more preferably about 2% to about
3.5%, by weight of the uncoated dosage form. This level of coating
will provide an elegant, serviceable coating to a wide variety of
dosage forms. To apply a heavier coating to tablets would not be
economical, and it might adversely affect disintegration of the
tablets or other properties. Too light a coating would not provide
optimal properties normally expected from a coating, for example,
improved friability or adequate taste masking.
[0037] For confections the coating level should be about 5% to
about 10% by weight of the uncoated confection. Seed coatings
should be in the range of about 3% to about 6% by weight of the
uncoated seeds. Fertilizers and pesticide tablets and granules
benefit from coating of 1% to about 3%, by weight of the uncoated
granules or tablets.
[0038] From the following examples is has been shown that the
coatings of the present invention may be applied successfully to
tablets having a wide variety of active ingredients incorporated
therein. For example, it has been reported that multivitamin
tablets are difficult to coat because of the lipophilic surface
properties of the vitamins. Similarly, ibuprofen is a challenging
active ingredient to coat. Tablets comprising both of these
difficult-to-coat active ingredients have been coated readily with
the instant invention, providing elegant tablets. Additionally, the
coatings have been applied to tablets which have been debossed with
letters or a logo without bridging which would hide, or even
obliterate, the debossed design.
[0039] An additional utility of the coating formulations of this
invention is as a replacement for sugar coating of tablets. A sugar
coating is applied primarily to increase the weight and/or size of
the tablet, but this is an old art which presents numerous
problems. It is, therefore, desirable to replace the traditional
sugar coating with a more easily applied coating. This coating
procedure has the additional advantage that no topcoat is required
to be applied as it is done with a sugar coating.
[0040] Storage of coated tablets under ambient temperature and
humidity and 40.degree. C. and 75% relative humidity for one to
three months has demonstrated that no significant degradation has
occurred. These tablets have disintegrated within the same length
of time as the same batch of newly coated tablets did, and in each
case provided dissolution rates and times substantially equal to
those of the uncoated tablets used as a substrate for coating. This
is an additional unexpected benefit of the coatings based on
propylene glycol alginate and microcrystalline cellulose, and it
differs from the known drawbacks of coating formulations in which
HPMC is the primary or only film-former.
[0041] All components of the formulation are typically
pharmaceutically acceptable, edible food grade materials.
[0042] The following examples, in which percentages are weight
percent and tablet hardness is in Kiloponds (Kp), are provided to
demonstrate the method of preparation and application of these
elegant coatings, but they are not intended to be limiting as to
amounts and the type of optional ingredients or the specific method
of application of the tablet coating described herein.
EXAMPLE 1
[0043] In a Patterson-Kelly twin shell blender were placed 48.0
grams of a blend of microcrystalline cellulose (Avicel.RTM. PH-105,
35 grams) and propylene glycol alginate (13 grams), 20 grams of
hydroxyethylcellulose (Aqualon.RTM.250L), 25 grams of triacetin,
and 3 grams of Pluronic F-68 (BASF). After the dry components had
been thoroughly blended, the blend was added slowly to the vortex
of 1011.1 grams deionized water which was stirred with a Lightnin'
mixer. The suspension was stirred for 2 hours at ambient
temperature to fully hydrate the composition. To this dispersion
was added 4.0 grams of red #40 liquid dispersion (Crompton and
Knowles). A Vector High Coater LDCS was charged with 1 Kg of each
of acetaminophen tablets and ibuprofen caplets. The coater was
operated at an inlet temperature of 84-85.degree. C., an outlet
temperature of 40-45.degree. C., and 14-15 rpm. During the
spraying, which required 56 minutes, a 3 weight percent coating,
based on the weight of the tablets & caplets was applied.
Friability of the tablets and caplets was 0% after 10 minutes.
EXAMPLES 2 THROUGH 5
[0044] By the method of Example 1, the dry components of each
formulation were dry blended and dispersed in deionized water after
which the triacetin and liquid components were added to the
dispersion. The dispersion was then sprayed on caplets which were
tested for friability. These examples are summarized in Table 1
below:
1 TABLE 1 Example: 2 3 4 5 Ingredients Weight (grams) Avicel PH-105
37 35 37 37 Hydroxyethyl- 22 20 22 22 cellulose PGA.sup.a 13 13 12
12 Pluronic F-68 3.5 3 -- 1.5 Red #40 24.5 4 6 7.5 dispersion
Triacetin -- 25 -- -- Mannitol.sup.b -- -- 18 15 Iota -- -- 5 5
carrageenan Deionized 1011.1 1011.1 1011.1 1011.1 water Hydration
time 2 hours >1 hour 6 hours >1 hour Caplets Charge (Kg)
Acetaminophen 0.67 1 0.67 0.67 Ibuprofen 0.67 1 0.67 0.67 Chlor-
0.67 -- 0.67 0.67 pheniramine Spray conditions Inlet 84-89.degree.
C. 83-85.degree. C. 63-69.degree. C. 69-74.degree. C. temperature
Outlet 36-40.degree. C. 40-42.degree. C. 38-39.degree. C.
30-32.degree. C. temperature Drum speed 14-15 rpm 15 rpm 11 rpm 10
rpm Time 54 minutes 57 minutes 55 minutes 58 minutes Coating 3 3 3
3 weight (%) Friability (10 minutes) Acetaminophen 0% 0% 0% NT
Ibuprofen 0% 0% slight NT Chlor- NT.sup.c -- NT NT pheniramine
.sup.aPolypropylene glycol alginate (Protonal .RTM. ester SD-LB,
Pronova) .sup.bGranular mannitol .sup.cNT = not tested
EXAMPLE 6
[0045] The components of this example were dry blended. The dry
blend was dispersed in deionized water, then sprayed on caplets
and/or tablets which were tested for friability. This example is
summarized in Table 2:
2 TABLE 2 Example: 6 Ingredients Weight (grams) Avicel PH-105 37
PGAa 13 Iota carrageenan 5 Hydroxyethylcellulose 22 Mannitol.sup.b
17.5 Pluronic F-68 3.5 Blue Lake #2 2 Deionized water 1150
Hydration time 2 hours Caplets Charge (Kg Ibuprofen 1
Chlorpheniramine 1 Spray conditions Inlet temperature 97-99.degree.
C. Outlet temperature 31-35.degree. C. Drum speed 12-13 rpm Time 62
minutes Coating weight % 3% Friability (10 minutes) Ibuprofen 0%
Chlorpheniramine 0% .sup.aPolypropylene glycol alginate (Protonal
.RTM. ester SD-LB, Pronova) .sup.bGranular mannitol
EXAMPLES 7 -13
[0046] By the method of Example 1, the dry components of each
formulation were dry blended then dispersed in deionized water. The
dispersion was then hydrated and sprayed on caplets which were
tested for friability, gloss and disintegration time. The examples
are summarized in Table 3 below.
EXAMPLES 14-30
[0047] These additional examples were also prepared and applied in
the manner of Examples 7-14. The resulting coating compositions are
set forth in Table 4 below.
3 TABLE 3 Example 7 8 9 10 11 12 13 Ingredients Percentage by
weight Avicel PH105 20 20 15 20 25 20 25 PGA.sup.a 30 40 50 40 30
30 35 HEC 20 10 5 -- -- 15 15 Lecithin.sup.b 3 3 3 -- 3 3 3
Maltodextrin M180 17 17 17 25 22 17 17 Iota Carrageenan 5 5 5 5 5 5
5 Red hydrophilic Iron Oxide 5 5 5 -- 15 10 -- Blue lake/Yellow
lake blend -- -- -- 10 -- -- -- % Solids 8 8 8 8 8 8 9 Caplets
Charged (Kg) Acetominophen 2 2 12 12 12 12 12 Inlet Temperature
(.degree. C.) 78-88 67-90 46-53 50-53 52-54 52-54 67-72 Exhaust
Temperature (.degree. C.) 35-41 29-36 33-36 32-38 32-36 34-36 30-35
RPM 13 15 9 9 9 8 13 Spray Rate (gm/ml) 12 19 55 66 72 67 11 Time
(minutes) 70 41 84 85 64 66 59 Coating weight (%) 3 3 3 3 3 3 3
Appearance (shine).sup.d 5 4 4 2 3 4 4 Friability (% - 10 minutes)
0 0 0 MC.sup.c MC.sup.c 0 0 Disintegration Time, 37 .degree. C.
(minutes) <5 <5 <5 <12 <5 <5 <5 .sup.aLow
viscosity propylene glycol alginate (Profoam .RTM., Pronova)
.sup.bHydroxylated soy lecithin .sup.cMinor Chipping .sup.d5 =
superior, 4 = acceptable; 3 = marginal; 2 = poor
[0048]
4 TABLE 4 Example: 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
30 Ingredients (%) By Weight Avicel PH-105 25 20 25 20 34 25 20 20
25 25 25 25 25 22 25 25 25 PGA.sup.a 35 35 35 30 13 26 25 25 13 13
13 20 18 26 20 15 20 Hydroxyethylcellulose 15 15 17 20 22 22 20 20
20 20 20 17 15 20 15 20 20 Iota carrageenan 5 5 5 5 12 12 12 12 15
15 15 12 12 12 12 10 10 Lecithin.sup.b 3 3 5 3 7 3 3 3 7 7 5 7 3 7
3 5 Maltodextrin 3 3 3 3 3 3 3 3 3 3 3 3 3 3 PIGMENT (Var) 5 10 10
5 5 7 10 10 5 7 7 7 5 8 8 10 10 Mannitol.sup.c 9 9 -- 17 4 2 7 10
10 6 10 3 -- -- -- Lactose 15 Croscarmellose 5 3 5 3 5 3 2 Calcium
carbonate 7 7 -- dicalcium Phosphate 5 11 5 PVP 29/32, 25, s603
.sup.aLow Viscosity propylene glycol alginate (Profoam .RTM.,
Pronova) .sup.bHydroxylated soy lecithin .sup.cGranular
mannitol
* * * * *