Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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FILM COATING COMPOSITIONS BASED ON TRIBASIC CALCIUM
PHOSPHATE
Technical field:
This invention relates to the field of coating compositions for substrates
like
pharmaceutical tablets, nutritional supplements, food products, confectionery,
agricultural
seeds for providing protection to the substrate from environmental conditions
like light,
humidity, atmospheric g.ases etc.
Background of the Invention:
Film coating is generally, a process of depositing a thin layer of material
onto a substrate
such as a pharmaceutical tablet to provide a protective barrier covering the
outer surface
and also to provide an aesthetic appearance to the product.
There is ample literature in the form of patents and published articles
available on fihn
coating and its compositions. There are various types of fihn coating
compositions known
in the art and have a wide range of applications in coating like
pharmaceutical tablets,
food products, agricultural seeds etc. Most of these compositions use certain
polymers
like HPMC, HPC, HEC, and other cellulosic polymers.
Japanese patent JP 148-59512 provides compositions for film coating based on
polyvinyl
alcohol as fihn forming polymers. US 3935326 filed in April 1974 describes the
coating
of core tablets with polymers selected from the group consisting of polyvinyl
alcohol,
polyvinyl pyrrolidone and solid polyethylene glycol. Subsequent to these
patents, US
patent no. 5,885,617 filed in June 1995 having the application priority of
GB9414045
(July 12, 1994) provides moisture barrier film coating compositions based on
polyvinyl
alcohol. Yet another US patent no. 5604282 filed in Dec 1994 provides a
strippable,
rewettable film coating generally comprising polyvinyl polymer, polyvinyl
alcohol and
other ingredients.
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However, all these compositions were found to be fairly sticky in nature,
making the film
coating process quite difficult. Some of these difficulties have been claimed
to be
resolved in the film coating compositions described in US6448323 filed in July
1999.
In addition to the above compositions based on polyvinyl alcohol, there have
been many
compositions known in the art of fihn coating based on various cellulosic
polymers.
All these polymers which have been used for film coating provide fairly tacky
coating
suspensions which when sprayed on the substrates like pharmaceutical tablets;
form a thin
film on the substrate. Inventors have tried to add lubricants like talc and
other inert
excipients like pigments/opacifiers etc to reduce the tackiness of the
polymers and to
increase the solid content thereby reducing the time of coating. However, the
problem of
tackiness still persists.
Even though various types of film coating compositions are known in the art
and are
available to the industry for wide range of applications; many of such
compositions use
expensive ingredients which may have restricted supplies or availability.
Therefore, there remains a long felt need in the art to develop cost-effective
film coating
compositions that eliminates the above mentioned drawbacks such as tackiness,
low
tensile strength and low spray rate etc. This forms the subject of the present
invention.
Object of the invention:
The objective of the invention is to provide dry fihn coating composition that
has a
smooth surface, shiny gloss, minimal tackiness, good film strength and
adhesion
properties and provides excellent protection to the substrate against various
environmental conditions like light, moisture and atmospheric gases.
Another objective of the invention is to provide cost-effective film coating
compositions
thereby making this composition available to a wide range of food and
medicinal
products.
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Further objective of the invention is to provide a method for coating the
substrates using
the composition of the invention.
Summary of the Invention:
In accordance with the above objectives, the present invention provides cost-
effective dry
film coating compositions comprising of tribasic calcium phosphate as one of
the
essential ingredient along with other commonly used polymers, plasticizers,
excipients
like suspending agents, pigments, lubricants, glidents, opacifiers, flavours,
sweetener etc.
for use in coating of pharmaceutical tablets, nutritional supplements, food
products,
confectionery, agricultural seeds and the like.
In another aspect, the invention provides a method of coating a substrate
using the
invented coating composition.
Detailed Description:
The invention will now be described in detail in connection with certain
preferred and
optional embodiments, so that various aspects thereof may be more fully
understood and
appreciated.
It is well known in the art of film coating that polyvinyl alcohol is a very
tacky polymer
which makes the coating process very difficult for the coating compositions
where
polyvinyl alcohol has been used as the main film forming polymer.
Thus the present inventors, on exploring various alternatives for a reliable
film coating
compositions, have been found that the use of an inert pharmaceutical
excipient, tribasic
calcium phosphate in film coating compositions reduces the tackiness of
polyvinyl
alcohol very significantly, thus makes the fihn coating process much simpler
and easy.
Even after reducing the polymer tackiness, use of tribasic calcium phosphate
still
provides good film strength and high film adhesion so that the resulting film
provides
much improved protection to the substrate.
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The present invention describes dry film coating compositions wherein an
inexpensive
and commonly used phannaceutical excipient, tribasic calcium phosphate has
been used
along with other commonly used polymers to achieve a low cost coating
composition.
Accordingly, dry film coating compositions of the present invention suitable
for use in
coating pharmaceutical tablets, nutritional supplements, food, confectionery
or
agricultural seeds comprises tribasic calcium phosphate in combination with
polymer
system and plasticizer. The invented composition has excellent film forming
ability and
film adhesion to the substrate. It has also been observed that the invented
composition
provides excellent protection to the substrate against various environmental
conditions
like light, moisture and atmospheric gases.
Advantageously, the tribasic calcium phosphate can be used in the composition
in a range
of about 2% to about 50% more preferably in a range of about 6% to about 40%
by
weight of the composition.
The present inventors have further experimented the compatibility of tribasic
calcium
phosphate with other polymers like HI'MC, HPC, HEC, methyl cellulose, ethyl
cellulose,
aqueous dispersion of ethyl cellulose, sodium alginate, alginic acid, sodium
carboxy
methyl cellulose and found that tribasic calcium phosphate is an excellent
excipient and
can easily be used with other polymers also with superior results. Thus, the
polymer
system of present inventive formulation may comprise one or more polymers as
mentioned above. The polymer system of present invention may present in a
range of
10% to 90%; more preferably in a range of about 15% to about 75% by weight of
the
composition. The film adhesion was found to be higher when the polymer was
mixed
with tribasic calcium phosphate than when used alone. The use of tribasic
calcium
phosphate,does not increase the viscosity of the coating suspension, hence,
the solid
content of the coating suspension can also be increased than using the polymer
alone thus,
making the coating process quite faster. It was further observed that in
certain
compositions based on tribasic calcium phosphate, the solid content of the
coating
suspension can be increased upto 25% w/w without having any adverse effect on
spray
characteristics.
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Tribasic calcium phosphate was found to be an excellent excipient for film
coating as it is
compatible with a wide variety of plasticizers without affecting the shelf
life of the
product and hence the composition may advantageously contain one or more
plasticizers.
Various plasticizers which have been used in different compositions, are
triacetin,
propylene glycol, various grades of polyethylene glycol, liquid paraffin,
diethyl phthalate,
dibutyl phthalate, triethyl citrate, lecithin, fractionated coconut oil,
castor oil etc. in
different concentrations ranging from 2% to 30% w/w. The more preferable range
is
about 5% to about 20% by weight of the composition.
Further, the inventors have also found that the addition of liquid
plasticizers like PEG 200
or PEG 400 or triacetin or castor oil or diethyl phthalate or dibutyl
phthalate etc. is much
easier in the coating compositions based on tribasic calcium phosphate. The
liquid
plasticizers get adsorbed onto tribasic calcium phosphate and does not make
the whole
composition wet. This nature of tribasic calcium phosphate helps in adding
higher
concentrations of liquid plasticizers (which is not possible in many known
compositions
in art) and also makes the manufacturing of coating composition much easier.
The composition of the present invention further includes a pigment /
opacifier in an
amount of 0% to 30% by weight of the composition.
Tribasic calcium phosphate is proved to be a useful excipient in fihn coating
compositions as it was found to be compatible with other commonly used
excipients in
film coating like talc, fumed silica, kaolin, magnesium stearate, stearic
acid, opacifiers
like titanium dioxide and calcium carbonate, colours (synthetic dyes, natural
colours, iron
oxide colours as well as candurin colours), flavours, sweeteners etc. The
product
performance and shelf life was found to be good when coating composition has
tribasic
calcium phosphate as one of the ingredient.
The invented composition further comprises flow aid selected from talc, fumed
silica,
kaolin, magnesium stearate, stearic acid or magnesium trisilicate, either
alone or in
combination of more than one ingredient. The flow aid is present in an amount
ranging
0% to 20% by weight of the composition.
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The dry film coating composition further comprises colouring agent selected
from lake
colours, soluble colours, iron oxide colours, candurin colours or natural
colours either
alone or a combination thereof. The amount of colouring agent may present in
the range
of 0% to 30% by weight of the composition.
A sweetener selected from sodium saccharin, sucrose, aspartame, neutrame or
dextrose,
may also present in the film coating composition either alone or in mixtures
thereof. The
sweetener may present in a range of about 0% to about 10% by weight of the
composition.
The film coating composition may further contain a flavouring agent in an
amount
ranging from 0% to 15% by weight of the composition. The flavouring agent
being either
encapsulated powder or liquid flavour suitable for pharmaceutical / food
applications can
be used.
Advantageously, the presence of tribasic calcium phosphate in film coating
composition
makes the product less hygroscopic and thus reduces the caking tendency of
various
polymers; many of those tend to pick moisture from atmosphere in high humidity
conditions and tend to cake. Thus, the presence of tribasic calcium phosphate
helps in
increased shelf life of the coating composition.
It has been farther observed that commercially available grades of tribasic
calcium
phosphate give satisfactory to good results, but the performance of the
coating
composition improved significantly once the micronized grade of tribasic
calcium
phosphate was used. The surface coverage by the resulting fihn, fihn
smoothness and
gloss level were comparatively better with the micronized grade of tribasic
calcium
phosphate. Therefore, micronized tribasic calcium phosphate with a micron size
of 10 to
200 microns can be used advantageously to achieve the desired results.
The invented composition can very easily be manufactured by dry mixing of
various
ingredients (mixing may need specific order of addition depending on the
ingredients
used), carrying out the colour matching exercise using spectrophotometric
colour scan
method.
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In another preferred embodiment, the invention describes a method for coating
substrates.
Accordingly, a method for coating substrates such as pharmaceutical tablets,
nutritional
supplements, food, confectionery, agricultural seeds, and the like, with a
film coating
composition comprising the steps of
a) mixing the coating composition into water or into organic solvents or into
a
combination of water and alcoholic solvents to form a smooth dispersion;
b) applying an effective amount of said coating dispersion onto said substrate
to
form a film on the said substrate, and
c) drying the film coating on said substrate.
In accordance with the above method, the dry mix composition can easily be
converted
into coating suspension by suspending in suitable solvent system using a
simple stirring
procedure. The suspension becomes ready for coating quite quickly when a
propeller
stirrer is used for suspension preparation.
The invented composition can easily be mixed with various solvent systems like
purified
water, a mixture of purified water and alcoholic solvents (like ethyl alcohol,
isopropyl
alcohol, methyl alcohol etc.), a mixture of alcoholic solvents and other
organic solvents
like methylene dichloride, acetone etc. The use of solvent system was found to
be mostly
governed by the use of polymer/polymer system and the nature of the substrate
to be
coated.
The invented composition can easily work in fairly wide range of film coating
process
conditions which can easily be controlled, monitored and reproduced. Once the
suspension is ready, it can easily be sprayed onto the substrate using
commonly used
spray equipments and the coating process can easily be carried out either in
conventional
(non perforated) coating pan, perforated coating pan (like Acela Cota) or in
fluid bed
coater.
Thus, the invention covers the novel film coating compositions and includes
coating
dispersions, the coated substrates, such as coated pharmaceutical tablets,
coated
nutritional supplements, coated food products, coated confectionery forms,
coated
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agricultural seeds etc and the method of making the dry fihn coating
compositions and the
method of making the coating dispersion of the invention.
The following examples, which include preferred embodiments, will serve to
illustrate the
practice of this invention, it being understood that the particulars shown are
by way of
example and for purpose of illustrative discussion of preferred embodiments of
the
invention.
The ranges of each component of the dry coating compositions of the invention
are as
follows, by weight:
Component Acceptable ranges (%) Preferred ranges (%)
Tribasic calcium phosphate 2-50 6-40
Polymer 10 - 90 15 - 75
Plasticizer 2-30 5-20
Talc 0-8 0-5
Pigment / Opacifier / Colour 0- 35 0- 30
The following examples illustrate the practice of invention. All units and
percentages in
the examples are given by weight.
EXAMPLE 1
General method for preparation of the coating composition and coating process:
The dry components of the following formulation were blended together in a dry
powder
mill or a blender, for 30 minutes, until an homogenous mixture achieved,
resulting in the
formulation of the inventive dry fihn coating composition.
Optionally, the dry film coating composition of the invention may be
granulated using a
planetary mixer. After the dry fihn coating composition was loaded into the
mixer,
sufficient water was slowly added during the mixing process until the
composition forms
slightly adherent granules. These granules were then passed through a 1-2 mm
screen and
then dried in an oven at 30 C until the moisture content below 5%. The
composition was
then sieved again through a 1-2 mm screen to make it ready for use in a
nondusting,
granular form.
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The composition may optionally be milled such as in a hammer mill, for
example. Other
methods of granulation, which may also be used, are spray granulation and
roller
compaction.
100 grams of the resulting film coating composition was dispersed into 400
grams of
distilled water to form an inventive coating dispersion (20% solids), and 500
grams of the
above dispersion was sprayed onto 3 kilograms of tablets using a coater to
form the
inventive coating on the tablets having a theoretical weight gain of 3%. The
tablets were
rotated in the coater at a rotation speed of 12 rpm. Hot air at 60 C to 65 C,
was used to
evaporate the solvent in the sprayed coating dispersion and to maintain the
tablets at
around 38 C. The spraying rate of coating dispersion during coating was 15
grams per
minute.
Upon completion of the coating process, the tablets showed a smooth surface
with
excellent logo definition. The film coating on the tablets possesses an
excellent long-
lasting shinny gloss, minimal tackiness, good film adhesion, and good tensile
strength.
Component Percentages Grams
Tribasic calcium phosphate 40 400
Polyvinyl alcohol 44 440
Polyethylene glycol 6000 16 160
Total 100% 1000
EXAMPLE 2
Component Percentages Grams
Tribasic calcium phosphate 20 200
Polyvinyl alcohol 44 440
Polyethylene glycol 4000 16 160
Titanium dioxide 12 120
Lake colour 8 80
Total 100% 1000
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EXAMPLE 3
Component Percentages Grams
Tribasic calcium phosphate 19 190
Polyvinyl alcohol 38 380
Polyethylene glycol 6000 8 80
Polyethylene glycol 400 5 50
Talo 5 50
Titanium dioxide 15 150
Iron oxide yellow 10 100
Total 100% 1000
EXAMPLE 4
Component Percentages Grams
Tribasic calcium phosphate 15 150
Polyvinyl alcohol 56 560
Polyethylene glyco14000 13 130
Talc 5 50
Iron oxide red 11 110
Total 100% 1000
EXAMPLE 5
Component Percentages Grams
Tribasic calcium phosphate 40 400
Polyvinyl alcohol 15 150
Polyethylene glycol 8000 17 170
Polyethylene glyco1400 8 80
Titanium dioxide 10 100
Lake colour 10 100
Total 100% 1000
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EXAMPLE 6
Component Percentages Grams
Tribasic calcium phosphate 15 150
HPMC 60 600
Polyethylene glycol 6000 15 150
Iron oxide yellow 10 100
Total 100% 1000
EXAMPLE 7
Component Percentages Grams
Tribasic calcium phosphate 12 120
HPMC 40 400
HPC 20 200
Triacetin 8 80
Talc 4 40
Titanium dioxide 11 110
Lake Colour 5 50
Total 100% 1000
EXAMPLE 8
Component Percentages Grams
Tribasic calcium phosphate 18 180
IIPMC 56 560
Ethyl cellulose (aq. dispersion) 6 (total solids) 60
Triacetin 8 80
Titanium dioxide 8 80
Lake Colour 4 40
Total 100% 1000
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EXANIPLE 9
Component Percentages Grams
Tribasic calcium phosphate 10 100
HPMC 55 550
Ethyl cellulose 5 50
Diethyl phthalate IO 100
Talc 7 70
Titanium dioxide 10 100
Iron oxide red 3 30
Total 100% 1000
EXAMPLE 10
Component Percentages Grams
Tribasic calcium phosphate 30 300
HPMC 30 300
Polyvinyl alcohol 15 150
Polyethylene glycol 400 10 100
Polyethylene glycol 6000 4 40
Iron oxide yellow 9 90
Lake Colour 2 20
Total 100% 1000
EXAMPLE 11
Component Percentages Grams
Tribasic calcium phosphate 8 80
HPMC 60 600
Polyethylene glycol 6000 12 120
Titanium dioxide 3 30
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Lake Colour 8 80
Flavour 8.5 85
Sodium saccharin 0.5 5
Total 100% 1000
EXAMPLE 12
Component Percentages Grams
Tribasic calcium phosphate 8 80
Polyvinyl alcohol 44 440
Polyethylene glycol 6000 14 140
Talc S 50
Iron oxide red 20 200
Flavour 8 80
Aspartame 1 10
Total 100% 1000
EXAMPLE 13
Component Percentages Grams
Tribasic calcium phosphate 20 200
Polyvinyl alcohol 40 400
Polyethylene glycol 6000 12 120
Soya Lecithin 3 30
Titanium dioxide 7 70
Candurin colour 18 180
Total 100% 1000
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EXAMPLE 14
Component Percentages Grams
Tribasic calcium phosphate 15 150
HPMC 56 560
Polyethylene glycol 6000 12 120
Talc 4 40
Titanium dioxide 5 50
Candurin colour 8 80
Total 100% 1000
EXAMPLE 15
Component Percentages Grams
Tribasic calcium phosphate 20 200
Polyvinyl alcohol 32 320
Soya lecithin 4 40
Polyethylene glycol 8000 15 150
Talc 5 50
Titanium dioxide 20 200
Lake Colour 4 40
Total 100% 1000
The coating formulations as described above (examples 2 to 15) are prepared
similarly in
accordance with the above method exemplified under example 1.
It will be evident to those skilled in the art that the invention is not
limited to the details
of the foregoing illustrative examples and that the present invention may be
embodied in
other specific forms without departing from the essential attributes thereof,
and it is
therefore desired that the present embodiments and examples be considered in
all respects
as illustrative and not restrictive, reference being made to the appended
claims, rather
than to the foregoing description, and all changes which come within the
meaning and
range of equivalency of the claims are therefore intended to be embraced
therein.
