DESCRIPTION
Orally Disintegrating Coated Tablet
TECHNICAL FIELD
[0001]
The present invention relates to a stable orally disintegrating coated tablet.
More particularly, the present invention relates to a stable orally disintegrating
coated tablet containing a drug, wherein the tablet is coated with a coating layer
containing a water-soluble substance and a polyvinyl alcohol resin of not less than
5% by weight based on the weight of the coating layer, the water-soluble substance
dissolving in an amount of 1 g or more in less than 10 mL of water at 20°C, having a
hydroxyl group(s) in its molecule, and having a molecular weight of not more than
200 per a unit hydroxyl group.
BACKGROUND ART
[0002]
Tablet coating, which is a treatment for forming a thin film-like substance on
a tablet surface, is carried out for the purpose of imparting various functions,
depending on the composition to be coated, such as improved appearance, water
resistance, improved friability, light stability, and distinguishability.
[0003]
Orally disintegrating tablets which rapidly disintegrate in an oral cavity have
now been developed as an easy-to-take formulation for patients with impaired
swallowing function due to various causes such as diseases, aging, and decreased
saliva production. The orally disintegrating tablets are special formulations which,
in view of easiness for patients to take, are required to have an overwhelmingly high
disintegration rate compared to that of general tablets and pursue high disintegration
rate. However, rapid disintegration properties and high tablet hardness are

generally contradictory properties, and therefore orally disintegrating tablets cause
chips and cracks of the tablets when divided because of their insufficient tablet
hardness and high friability, and it has been pointed out that the orally disintegrating
tablets have a problem in handling at dispensing sites. Further, tablets are subject to
influence of storage environments such as light, temperature, and humidity because
they are stored in the unpacked form in a divider before being automatically divided
and are stored in the simply packed form after being divided, and there has been a
disadvantage that drugs sensitive to these external environments are inapplicable.
In this regard, for example, in cases where a light-unstable drug is tableted, the tablet
is generally stabilized by being coated with a coating layer to which a light shading
agent is added, but in the case of the orally disintegrating tablets, there is a concern
that disintegration is delayed by the coating layer, and stabilization by light shading
coating on the tablet itself is difficult.
[0004]
In addition, many of the orally disintegrating tablets cause a volume
expansion under high humidity because the orally disintegrating tablets are provided
with rapid disintegration properties by the addition of a hygroscopic excipient and a
powerful disintegrator. Therefore, in order for an orally disintegrating tablet to be a
coated tablet, it requires not only rapid disintegration properties but also extensibility
of the coating layer, but at present there are no conventionally known coated
compositions which have an ability to withstand the expansion of a tablet while
maintaining orally disintegrating properties.
[0005]
On the other hand, it is conventionally known that polyvinyl alcohol is used
as a coating polymer in the general tablets. There are disclosures of preventing
crack occurrence in a coating layer during storage by coating an expansible tablet
with polyvinyl alcohol (for example, Patent Document 1). There are also

disclosures of preventing crack occurrence in a coating layer during storage by
coating an expansible tablet with polyvinyl alcohol with saccharides and a viscosity
reducer being added (for example, Patent Document 2). Further, there are
disclosures of reducing cracks of the tablet by providing a coating layer of water-
soluble polymer and saccharides as an intermediate layer of a sugar-coated tablet (for
example, Patent Document 3). However, all these reports only disclose that
polyvinyl alcohol films exhibit excellent extension and do not disclose that when
polyvinyl alcohol is coated on an orally disintegrating tablet, the tablet exhibits such
an excellent rapid solubility that allows easy taking in an oral cavity.
[0006]
On the other hand, another example of the easy-to-take formulation for the
above-described purpose is an orally disintegrating film preparation which
disintegrates in an oral cavity. As the film preparation, compositions obtained by
adding saccharides to water-soluble polymer such as hydroxypropylmethylcellulose
are disclosed (for example, Patent Document 4), but these disclosures mainly focus
on disintegration properties and do not describe film extension. Rather, film
extension in the film preparation, for example, causes undesirable forms such as a
softened film, and is essentially different from the requirements for the coating layer
of an orally disintegrating tablet.
[0007]
Further, there are disclosures of methods of forming a coating layer by
melting soluble powder such as low melting point polymer in order to improve the
insufficient tablet hardness and high friability of an orally disintegrating tablet (for
example, Patent Document 5). However, melting technique, by which it is difficult
to form a coating layer uniformly on the whole tablet, is inadequate as a light
stabilization method. As a dosing preparation for a drug absorbed via oral mucosa,
preparations obtained by coating an orally disintegratable core with a composition

composed of gellan gum are disclosed (for example, Patent Document 6). However,
the extension of the coating layer is not reported at all.
[0008]
On the other hand, as a method of stabilizing nalfurafine hydrochloride, there
are disclosures of solid preparations containing sodium thiosulfate, saccharides or
sugar alcohols, and low-substituted hydroxypropylcellulose, the disclosures also
describing that the preparations are coated tablets (for example, Patent Document 7
and Patent Document 8). However, they only disclose that general coated
compositions can be coated and do not describe at all the excellent rapid
disintegration properties necessary for orally disintegrating tablets or the effect of
preventing cracks in a coating layer during storage, and therefore the present
invention cannot easily be inferred from these reports.
PRIOR ART DOCUMENTS
Patent Documents
[0009]
[Patent Document 1] JP 2007-091620 A
[Patent Document 2] JP 54-28812 A
[Patent Document 3] JP 2000-169365 A
[Patent Document 4] JP 11-116469 A
[Patent Document 5] JP 2005-524654 W
[Patent Document 6] JP 2005-519924 W
[Patent Document 7] WO 2008/133330
[Patent Document 8] WO 99/02158
SUMMARY OF THE INVENTION
PROBLEMS TO BE SOLVED BY THE INVENTION
[0010]
It is an object of the present invention to provide a stable orally disintegrating

coated tablet which does not cause a crack in the coating layer even when the orally
disintegrating tablet has been swollen by moisture absorption under high humidity,
while ensuring rapid disintegration properties in an oral cavity. It is also an object
of the present invention, in the case of an orally disintegrating tablet containing a
light-unstable drug, to suppress the degradation of the drug by blending a light
shading agent in the coating layer.
MEANS FOR SOLVING THE PROBLEMS
[0011]
Tablet coating is carried out for the purpose of, for example, improving
appearance, imparting water resistance, improving friability, light stabilization, and
imparting distinguishability. However, orally disintegrating tablets are generally
expanded by moisture absorption particularly under high humidity by their nature to
have rapid disintegration properties, and therefore it became clear that cracks occur
in the coating layer during storage when coating polymer such as widely-used
hydroxypropylmethylcellulose is used. It also became clear that by coating the
tablets, disintegration of the coating layer becomes rate-limiting, making it difficult
to maintain the rapid disintegration properties.
[0012]
Thus, the present inventors intensively studied in order to develop a stable
orally disintegrating coated tablet which has rapid disintegration properties and
further does not cause a crack even under high humidity, and consequently
discovered that a stable orally disintegrating coated tablet which has excellent rapid
disintegration properties and further does not cause a crack even under high humidity
can be obtained only when using the combination of polyvinyl alcohol resin, among
polymers used for coating the tablet, and a water-soluble substance dissolving in an
amount of 1 g or more in less than 10 mL of water at 20°C, having a hydroxyl
group(s) in its molecule, and having a molecular weight of not more than 200 per a

unit hydroxyl group (hereinafter, also referred to as the water-soluble substance of
the present invention for short). The present inventors also discovered that in the
case of the tablet containing a light-unstable drug, degradation of the drug is
suppressed by blending a light shading agent in the coating layer, thereby completing
the present invention.
[0013]
Thus, the present invention relates to the invention as described below.
[1] A stable orally disintegrating coated tablet containing a drug, wherein the tablet is
coated with a coating layer containing a water-soluble substance and a polyvinyl
alcohol resin of not less than 5% by weight based on the weight of the coating layer,
the water-soluble substance dissolving in an amount of 1 g or more in less than 10
mL of water at 20°C, having a hydroxyl group(s) in its molecule, and having a
molecular weight of not more than 200 per a unit hydroxyl group.
[2] The stable orally disintegrating coated tablet according to [1], wherein said water-
soluble substance is at least one of saccharides, sugar alcohols, and polyhydric
alcohols.
[3] The stable orally disintegrating coated tablet according to [1], wherein said water-
soluble substance is at least one of maltose, maltitol, sorbitol, xylitol, glycerin,
fructose, glucose, lactitol, isomaltose, lactose, erythritol, mannitol, trehalose, sucrose,
and polyethylene glycol having an average molecular weight of not more than 400.
[4] The stable orally disintegrating coated tablet according to [1], wherein the
polyvinyl alcohol resin in the coating layer has a content of 10 to 60% by weight
based on the weight of the coating layer.
[5] The stable orally disintegrating coated tablet according to [1], characterized in
that weight ratio of the polyvinyl alcohol resin in the coating layer to said water-
soluble substance is 1:0.1 to 1:9.
[6] The stable orally disintegrating coated tablet according to [1], characterized in

that the coating layer disintegrates in an oral cavity within 18 seconds and the orally
disintegrating coated tablet disintegrates in an oral cavity within 60 seconds.
[7] The stable orally disintegrating coated tablet according to [1], characterized in
that the coating layer contains a light shading agent.
[8] The stable orally disintegrating coated tablet according to [7], wherein the light
shading agent is at least one of titanium oxide, red ferric oxide, yellow ferric oxide,
black iron oxide, talc, and kaolin.
[9] The stable orally disintegrating coated tablet according to [7], characterized in
that the light shading agent in the coating layer has a content of 0.1 to 40% by weight
based on the weight of the coating layer.
[10] The stable orally disintegrating coated tablet according to [1], wherein the drug
is at least one of nalfurafine, amlodipine, donepezil, ebastine, selegiline, famotidine,
irsogladine, brotizolam, olanzapine, lansoprazole, bepotastine, ramosetron,
tamsulosin, naftopidil, polaprezinc, voglibose, rizatriptan, midodrine, risperidone,
ondansetron, loratadine, montelukast, azulene sulfonate, etizolam, enalapril, captopril,
glibenclamide, chlormadinone acetate, doxazosin, triazolam, domperidone, ketotifen,
bromperidol, pravastatin, simvastatin, loperamide, lisinopril, rilmazafone,
precipitated calcium carbonate, magnesium oxide, mecobalamin, alfacalcidol,
bromocriptine, and pramipexole, and pharmaceutically acceptable salts and solvates
thereof.
EFFECTS OF THE INVENTION
[0014]
The present invention provides an orally disintegrating coated tablet of which
insufficient tablet hardness, high friability, or degradation by external environmental
factors such as light are improved. More particularly, the present invention
provides a stable orally disintegrating coated tablet which does not cause a crack in
the coating layer even when the orally disintegrating tablet has been swollen by

moisture absorption under high humidity, while ensuring rapid disintegration
properties in an oral cavity. In the case of an orally disintegrating tablet containing
a light-unstable drug, degradation of the drug can be suppressed by blending a light
shading agent in the coating layer. These effects allow single-dose packaging of the
orally disintegrating tablet which hitherto could not be packaged in a single-dose
pack, which in turn improves drug compliance of patients and enhances therapeutic
effects.
BEST MODE FOR CARRYING OUT THE INVENTION
[0015]
The orally disintegrating coated tablet of the present invention will now be
described.
Polyvinyl alcohol resin used in the present invention refers to polyvinyl alcohol
(PVA) and derivatives or copolymers thereof, and may be generally commercially
available one. Specific examples of commercial products of polyvinyl alcohol
include, for example, Gohsenol (registered trademark) EG05, EG25, EG30, and
EG40 produced by Nippon Synthetic Chemical Industry Co., Ltd.; polyvinyl
alcohols 4-88, 5-88, 8-88, 26-88, and 40-88 produced by Merck; and PVA-102, 103,
105, 110, 117, 120, 124, HC, 203, 205, 210, 217, 220, 224, 235, L-8, L-9, L-9-78, L-
10, and PVA-505 produced by Kuraray Co., Ltd. Specific examples of commercial
products of the copolymers of polyvinyl alcohol include, for example, polyvinyl
alcohol-polyethylene glycol graft copolymer, Kollicoat (registered trademark) IR,
produced by BASF. Specific examples of commercial products of the derivatives
of polyvinyl alcohol include, for example, polyvinyl alcohol copolymers,
POVACOAT (registered trademark) Type F, Type R, and Type L produced by Daido
Chemical Corporation. A polymer obtained by introducing a polyhydric alcohol
group(s) such as glycerin into the side chain of polyvinyl alcohol to reduce the
intramolecular interaction of the polyvinyl alcohol, so as to improve a property such

as solubility or extensibility of the film formed using the polymer, may also be used.
One or more of these specific examples may be used in combination.
[0016]
The water-soluble substance of the present invention dissolving in an amount
of 1 g or more in less than 10 mL of water at 20°C refers to a water-soluble
substance which exhibits, when shaken vigorously for 30 seconds at five-minute
intervals at 20 ± 5°C in accordance with the description about solubility in the
Japanese Pharmacopoeia 15th Edition, General Notices, page A-13, such rapid
solubility that less than 10 mL of water is sufficient to dissolve 1 g of the substance
within 30 minutes. Table 1 shows the list of the terms representing solubility
described in the Japanese Pharmacopoeia 15th Edition, General Notices, page A-13.
The substances classified as "Very soluble" or "Freely soluble" in Table 1 are
suitably used.
[0017]

The water-soluble substance which has a hydroxyl group(s) in its molecule
and has a molecular weight of not more than 200 per a unit hydroxyl group means
that the value obtained by dividing the molecular weight by the number of a
hydroxyl groups in the molecule is not more than 200. When the value is more than
200, sufficient interactions with a polyvinyl alcohol resin cannot be expected, so that
extensibility cannot be imparted to a coating layer.

[0019]
As the water-soluble substance of the present invention, saccharides, sugar
alcohols, and polyhydric alcohols are preferred. Examples of these include, for
example, maltose, maltitol, sorbitol, xylitol, glycerin, fructose, glucose, lactitol,
isomaltose, lactose, erythritol, mannitol, trehalose, sucrose, and polyethylene glycol
having an average molecular weight of not more than 400. In view of low
hygroscopicity, maltose, maltitol, lactitol, lactose, erythritol, mannitol, trehalose, and
isomaltose are preferred; lactose, mannitol, maltitol, and lactitol are more preferred.
One or more of these specific examples may be used in combination.
[0020]
The content of polyvinyl alcohol resin in the coating layer of the present
invention can be not less than 5% by weight, preferably 10 to 60% by weight, and
more preferably 10 to 40% by weight, based on the weight of the coating layer.
When the content of polyvinyl alcohol resin is less than 5% by weight based on the
weight of the coating layer, the film formability of polyvinyl alcohol is lost, resulting
in that tablets adhere to each other during production and cracks occur in the coating
layer under high humidity.
[0021]
The weight ratio of polyvinyl alcohol resin to the water-soluble substance of
the present invention in the coating layer of the present invention is not particularly
restricted, but in view of disintegration properties and film formability of polyvinyl
alcohol resin, it is preferably 1:0.1 to 1:9, more preferably 1:0.2 to 1:6, and still more
preferably 1:0.4 to 1:4.
[0022]
The stable orally disintegrating coated tablet of the present invention means
that cracks are unlikely to occur in the coating layer even when the orally
disintegrating tablet has been swollen by moisture absorption under high humidity.

Unlikelihood of cracks occurring in the coating layer can be evaluated by allowing
the orally disintegrating coated tablet to stand at 40°C under 75% RH (Relative
Humidity) atmosphere for 24 hours and checking the appearance of the coating layer.
The extension rate of such coating layer can be 1% or more, preferably 2% or more,
and more preferably 4% or more. The extension rate of the coating layer can be
determined by measuring a film of 10 mm in width and about 0.075 mm in thickness
with a tensile tester (Tensilon) at 25 °C under 60% RH atmosphere at a tensile speed
of 100 mm/min, the film being obtained by casting a solution or suspension having a
solid content of the coated composition of about 30% by weight on a glass surface
using an applicator (YBA type Baker applicator, 0 to 1 mm) at 0.5 mm and drying.
[0023]
The coating layer of the present invention can optionally contain a light
shading agent besides the above-mentioned components. Examples of the light
shading agent include, for example, titanium oxide, red ferric oxide, yellow ferric
oxide, black iron oxide, talc, and kaolin; preferably, the addition of titanium oxide,
red ferric oxide, and yellow ferric oxide produces a sufficient light shading effect.
One or more of these specific examples may be used in combination. These light
shading agents, when blended in large amounts, cause the loss of film extensibility,
and when blended in too small amounts, do not produce a sufficient addition effect;
therefore the content of the light shading agent can be 0.1 to 40% by weight,
preferably 1 to 35% by weight, and more preferably 5 to 30% by weight, based on
the weight of the coating layer.
[0024]
Besides the above-mentioned components, pharmaceutically acceptable
additives can optionally be added to the coating layer of the present invention as long
as the effects of the present invention are not impaired. Examples of such additives
include, for example, excipients, disintegrators, binders, corrigents, flavoring agents,

coloring agents, or lubricants. Examples of excipients include, for example,
starches such as corn starch and potato starch, microcrystalline cellulose, and light
anhydrous silicic acid. Examples of disintegrators include, for example, partially
pregelatinized starch, carmellose calcium, crospovidone, low-substituted
hydroxypropylcellulose, croscarmellose sodium, and sodium carboxymethyl starch.
Examples of binders include, for example, polyvinyl pyrrolidone,
hydroxypropylmethylcellulose, hydroxypropylcellulose, powdered acacia, gelatin,
pullulan, carmellose sodium, ethyl cellulose, and aminoalkyl methacrylate copolymer.
Examples of corrigents include, for example, aspartame, sucralose, sodium saccharin,
glycyrrhizin dipotassium, stevia, thaumatin, and citric acid. Examples of flavoring
agents include, for example, menthol, peppermint, lemon, lemon-lime, orange,
peppermint oil, and various flavors. Examples of coloring agents include, for
example, tar dye, turmeric extract, caramel, carotene solution, beta-carotene, copper
chlorophyll, and riboflavin. Examples of lubricants include, for example,
surfactants such as polyethylene glycol, liquid paraffin, silicone, and long-chain fatty
acid ester, and waxes such as beeswax, carnauba wax, and paraffin. These additives
are only illustrative and not restrictive at all. Such additives can be added to the
inner and outer surface of the coating layer of the present invention.
[0025]
In a coating operation of the stable orally disintegrating coated tablet of the
present invention, dry coating methods or wet coating methods can be used.
Examples of dry coating methods include, for example, the method of coating using
a coating layer as an intermediate when tableting, as described in JP 2005-529645 W.
Examples of wet coating methods include the method of coating by spraying a
coating solution onto the tablet surface and drying. The coating solution is prepared
by dissolving or suspending a coating layer composition which contains the water-
soluble substance of the present invention and a polyvinyl alcohol resin of not less

than 5% by weight based on the weight of the coating layer in water or solvents such
as ethanol and methanol. These solvents can be used alone or in combination. In
the process of coating the surface of the orally disintegrating tablet, commonly-used
apparatuses are used; for example, a pan coating apparatus can be used. Although
the operating conditions are not restricted, in the case of an orally disintegrating
tablet with high friability, a coating layer can be formed uniformly even at the edge
of the tablet by setting the pan rotation at below normal speed. Depending on the
shape and size of the preparations, the thickness of the coating layer to be formed, in
view of rapid disintegration properties, can be 200 µm or less, preferably 100 µm or
less, and more preferably 50 µm or less.
[0026]
For the oral disintegration time of an orally disintegrating tablet, objective
values can be obtained by measuring the time until the tablet has been completely
disintegrated by saliva without water or being chewed in the oral cavity of a healthy
adult male(s) and female(s) and averaging the measurements of three or more
subjects. "Tablet has been completely disintegrated" means the point when the
subjects no longer feel a foreign body sensation in the oral cavity. Orally
disintegrating tablets are generally designed to disintegrate within 60 seconds
without water in an oral cavity, as described in Patricia Van Arnum, "Advancing
ODT Technology," Pharmaceutical Technology, Vol. 3, No. 10, pp. 66-76, 2007
(published on October 2, 2007). Therefore, the oral disintegration time of an orally
disintegrating coated tablet can be less than 60 seconds, preferably less than 50
seconds, and more preferably less than 40 seconds.
[0027]
The oral disintegration time of a coating layer can be determined by firstly
measuring the oral disintegration time of an orally disintegrating coated tablet,
separately measuring the oral disintegration time of the inner core portion obtained

by cutting the coating layer of the orally disintegrating coated tablet, and then
subtracting the disintegration time of the inner core portion from the disintegration
time of the orally disintegrating coated tablet. Since the oral disintegration time of
commercially available orally disintegrating tablets is about from 10 seconds to 42
seconds, as described in Okimoto, "The Pharmaceutical Monthly", Jiho Inc., Vol. 50
No. 11, pp. 47-55 (published on October 1, 2008), in order for the oral disintegration
time of an orally disintegrating coated tablet to be less than 60 seconds, the oral
disintegration time of a coating layer can be less than 18 seconds, preferably less
than 15 seconds, and more preferably less than 12 seconds. The orally
disintegrating coated tablet of the present invention is not limited to being taken
without water, and may be taken with water.
[0028]
The inner core in the present invention, that is, the orally disintegrating tablet
is not particularly restricted with regard to its preparation method and composition as
long as the disintegration time in an oral cavity is about 1 to 42 seconds. For
example, those which are prepared by conventional methods in the art of preparation
such as direct tableting method, indirect tableting method, and molding method can
be used. Examples of such preparation methods include, for example, the
preparation method of obtaining porous tablets by tableting wet particles, the
preparation method utilizing physicochemical properties such as crystallization of
saccharides, the preparation method using a lyophilization technique, the preparation
method utilizing a disintegrator such as crospovidone, and the preparation method
using an external lubricant method.
[0029]
The drug of the stable orally disintegrating coated tablet in the present
invention is not particularly limited, and not restricted as long as it is a drug having
pharmacological activity. For example, the drug can contain as a drug at least one

of nalfurafine, amlodipine, donepezil, ebastine, selegiline, famotidine, irsogladine,
brotizolam, olanzapine, lansoprazole, bepotastine, ramosetron, tamsulosin, naftopidil,
polaprezinc, voglibose, rizatriptan, midodrine, risperidone, ondansetron, loratadine,
montelukast, azulene sulfonate, etizolam, enalapril, captopril, glibenclamide,
chlormadinone acetate, doxazosin, triazolam, domperidone, ketotifen, bromperidol,
pravastatin, simvastatin, loperamide, lisinopril, rilmazafone, precipitated calcium
carbonate, magnesium oxide, mecobalamin, alfacalcidol, bromocriptine, and
pramipexole, and pharmaceutically acceptable salts and solvates thereof. Among
them, when at least one of nalfurafine, amlodipine, ebastine, selegiline, brotizolam,
ramosetron, midodrine, montelukast, azulene sulfonate, etizolam, bromperidol,
mecobalamin, alfacalcidol, bromocriptine, and pramipexole, and pharmaceutically
acceptable salts and solvates thereof is contained as a drug, it is preferable to add a
light shading agent to the present coating layer because they are unstable to light.
[0030]
An example of the method of producing an orally disintegrating tablet
containing nalfurafine or a pharmaceutically acceptable salt and/or solvate thereof is
that an orally disintegrating tablet can be prepared by granulating powder mannitol
(such as PEARLITOL (registered trademark) 50C produced by Roquette Japan K.K.)
and crospovidone (such as Kollidon CL produced by BASF), mixing the resulting
granules with the other granulated granules obtained by granulating granular
mannitol (such as PEARLITOL (registered trademark) 300DC produced by Roquette
Japan K.K.) and nalfurafine or a pharmaceutically acceptable salt and/or solvate
thereof, and tableting the resulting mixture. By setting the blending ratio of powder
mannitol to granular mannitol at about 1:9 to 1:1 in weight ratio, the orally
disintegrating tablet can have excellent tabletability and disintegration properties.
In addition, a stabilizing agent can be blended for ensuring the stability of nalfurafine
or a pharmaceutically acceptable salt and/or solvate thereof in the preparation; for

example, sodium thiosulfate can be blended. The granulated granules of nalfurafine
or a pharmaceutically acceptable salt and/or solvate thereof and granulated mannitol
can be produced by the wet granulation method comprising the steps of dissolving or
suspending, for example, nalfurafine or a pharmaceutically acceptable salt and/or
solvate thereof and sodium thiosulfate together in water or a pharmaceutically
acceptable solvent and adding the resultant to granulated mannitol. In the wet
granulation, commonly-used apparatuses are used; for example, a fluidized bed
granulator, tumbling fluidized bed granulator, stirring granulator, cylindrical
extrusion granulator, and wet extrusion granulator can be used. In the step of
tableting, commonly-used apparatuses are used; for example, a single punch
tableting machine and rotary tableting machine can be used. The molding pressure
in tableting may be set such that the tablet has enough hardness that does not pose a
problem in coating operation. Although the shape of the tablet is also not
particularly restricted, a WR tablet tends to have improved friability.
EXAMPLES
[0031]
The present invention will now be described by way of examples to clarify its
excellent effects, but the present invention is not restricted thereto.
[0032]
Reference Example 1
Mannitol (PEARLITOL 300DC, Roquette Japan K.K.) was weighed in an
amount of 96.745 parts by weight (hereinafter, abbreviated as "parts" and the same
shall apply hereinafter unless otherwise noted.), sieved through Mesh with 1 mm
openings, and loaded into a fluidized bed granulator (FLO-5, Freund Industrial Co.,
Ltd.). Next, onto these granules, the spray solution obtained by dissolving 0.005
parts of nalfurafine hydrochloride and 0.1 parts of sodium thiosulfate hydrate in
distilled water was sprayed to produce granulated granules. Mannitol

(PEARLITOL 50C, Roquette Japan K.K.) was then weighed out in an amount of
25.87 parts, sieved through Mesh with 1 mm openings, and loaded into a stirring
granulator (NMG-3L, NARA MACHINERY CO., LTD.) together with 6.5 parts of
crospovidone (Kollidon CL, BASF). Subsequently, the resultant was granulated
while adding thereto distilled water in which 0.13 parts of red ferric oxide (Kishi
Kasei) was dispersed to produce granulated material. The granulated granules
produced with the fluidized bed granulator and the granulated granules produced
with the stirring granulator were treated individually using Comil to obtain sized
granules. To 129.35 parts of the sized granules, 0.65 parts of magnesium stearate
(Taihei Chemical Industrial Co., Ltd.) was added and mixed for five minutes. The
granules obtained were made into WR tablets of 130 mg using a tableting machine
(Corrects, KIKUSUI SEISAKUSHO LTD.).
[0033]
Example 1
Ten parts of PVA (polyvinyl alcohol 4-88, Merck) and 90 parts of maltitol
(MALTISOR BP200, Roquette Japan K.K.) were dissolved in distilled water to
prepare a coating solution having a solid content of 10% by weight. Into a film
coating machine (DRC-200, Powrex Corporation), 200 g of the orally disintegrating
tablets prepared in Reference Example 1 was loaded, and the coating solution was
sprayed thereonto to provide 131.95 mg of orally disintegrating coated tablets having
1.95 mg of coating layers per 130 mg of tablets.
[0034]
Example 2
Coating was carried out in the same manner except that an aqueous solution
having a solid content of 10% by weight composed of 60 parts of a polyvinyl alcohol
resin, POVACOAT (TYPE F, Daido Chemical Corporation), 5 parts of glycerin
(Japanese Pharmacopoeia concentrated glycerin, Asahi Denka Kogyo K.K.), and 35

parts of lactose (Pharmtose 200M, DMV) was used in place of the coating solution in
Example 1 to provide 133.9 mg of orally disintegrating coated tablets having 3.9 mg
of coating layers per 130 mg of tablets.
[0035]
Example 3
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 60 parts of PVA, 6 parts of
glycerin, and 34 parts of crospovidone (Kollidon CLSF, BASF) was used in place of
the coating solution in Example 1 to provide 133.9 mg of orally disintegrating coated
tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0036]
Comparative Example 1
Coating was carried out in the same manner except that an aqueous solution
having a solid content of 10% by weight composed of 60 parts of PVA and 40 parts
of PEG6000 (NOF CORPORATION) was used in place of the coating solution in
Example 1 to provide 133.9 mg of coated tablets having 3.9 mg of coating layers per
130 mg of tablets.
[0037]
Comparative Example 2
Coating was carried out in the same manner except that an aqueous solution
having a solid content of 10% by weight composed of 60 parts of PVA and 40 parts
of sodium lauryl sulfate (Nikko Chemicals Co., Ltd.) was used in place of the coating
solution in Example 1 to provide 133.9 mg of coated tablets having 3.9 mg of coating
layers per 130 mg of tablets.
[0038]
Comparative Example 3
Coating was carried out in the same manner except that a water dispersion

having a solid content of 10% by weight composed of 60 parts of PVA and 40 parts
of low-substituted hydroxypropylcellulose (L-HPC) (LH-31, Shin-Etsu Chemical Co.,
Ltd.) was used in place of the coating solution in Example 1 to provide 133.9 mg of
coated tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0039]
Comparative Example 4
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 60 parts of PVA and 40 parts
of crystal cellulose (CEOLUS PH-101, Asahi Kasei Chemicals Corporation) was
used in place of the coating solution in Example 1 to provide 133.9 mg of coated
tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0040]
Comparative Example 5
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 60 parts of PVA and 40 parts
of talc (Crown talc PP, Matsumura Sangyo Co., Ltd.) was used in place of the
coating solution in Example 1 to provide 133.9 mg of coated tablets having 3.9 mg of
coating layers per 130 mg of tablets.
[0041]
Comparative Example 6
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 60 parts of PVA and 40 parts
of crospovidone was used in place of the coating solution in Example 1 to provide
133.9 mg of coated tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0042]
Comparative Example 7
Coating was carried out in the same manner except that an aqueous solution

having a solid content of 10% by weight composed of 3 parts of PVA and 97 parts of
maltitol was used in place of the coating solution in Example 1.
[0043]
Example 4
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 60 parts of PVA, 2.5 parts of
glycerin, and 37.5 parts of low-substituted hydroxypropylcellulose (L-HPC) (LH-31,
Shin-Etsu Chemical Co., Ltd.) was used in place of the coating solution in Example 1
to provide 133.9 mg of orally disintegrating coated tablets having 3.9 mg of coating
layers per 130 mg of tablets.
[0044]
Example 5
Coating was carried out in the same manner except that an aqueous solution
having a solid content of 10% by weight composed of 70 parts of PVA and 30 parts
of maltitol was used in place of the coating solution in Example 1 to provide 133.9
mg of orally disintegrating coated tablets having 3.9 mg of coating layers per 130 mg
of tablets.
[0045]
Example 6
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 20 parts of PVA, 50 parts of
maltitol, 27 parts of titanium oxide (HA-R, Freund Industrial Co., Ltd.), and 3 parts
of red ferric oxide was used in place of the coating solution in Example 1 to provide
132.6 mg of orally disintegrating coated tablets having 2.6 mg of coating layers per
130 mg of tablets.
[0046]
Example 7

Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 40 parts of
maltitol, 27 parts of titanium oxide, and 3 parts of red ferric oxide was used in place
of the coating solution in Example 1 to provide 133.9 mg of orally disintegrating
coated tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0047]
Example 8
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 40 parts of PVA, 30 parts of
maltitol, 27 parts of titanium oxide, and 3 parts of red ferric oxide was used in place
of the coating solution in Example 1 to provide 133.9 mg of orally disintegrating
coated tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0048]
Example 9
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 38 parts of
maltitol, 27 parts of titanium oxide, 3 parts of red ferric oxide, and 2 parts of silicone
(SH200C FLUID 100CS, Dow Corning Toray) was used in place of the coating
solution in Example 1 to provide 133.9 mg of orally disintegrating coated tablets
having 3.9 mg of coating layers per 130 mg of tablets.
[0049]
Example 10
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 20 parts of
maltitol, 20 parts of lactitol (Lactitol MC, Danisco Japan Ltd.), 27 parts of titanium
oxide, and 3 parts of red ferric oxide was used in place of the coating solution in
Example 1 to provide 133.9 mg of orally disintegrating coated tablets having 3.9 mg

of coating layers per 130 mg of tablets.
[0050]
Example 11
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 40 parts of
lactitol, 27 parts of titanium oxide, and 3 parts of red ferric oxide was used in place
of the coating solution in Example 1 to provide 133.9 mg of orally disintegrating
coated tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0051]
Example 12
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 20 parts of PVA, 45 parts of
lactitol, 27 parts of titanium oxide, 3 parts of red ferric oxide, and 5 parts of polishing
wax (103, Freund Industrial Co., Ltd.) was used in place of the coating solution in
Example 1 to provide 133.9 mg of orally disintegrating coated tablets having 3.9 mg
of coating layers per 130 mg of tablets.
[0052]
Example 13
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 40 parts of
trehalose (Trehalose G, Asahi Kasei Chemicals Corporation), 27 parts of titanium
oxide, and 3 parts of red ferric oxide was used in place of the coating solution in
Example 1 to provide 133.9 mg of orally disintegrating coated tablets having 3.9 mg
of coating layers per 130 mg of tablets.
[0053]
Example 14
Coating was carried out in the same manner except that a water dispersion

having a solid content of 10% by weight composed of 30 parts of PVA, 40 parts of
mannitol (PEARLITOL 50C, Roquette Japan K.K.), 27 parts of titanium oxide, and 3
parts of red ferric oxide was used in place of the coating solution in Example 1 to
provide 133.9 mg of orally disintegrating coated tablets having 3.9 mg of coating
layers per 130 mg of tablets.
[0054]
Example 15
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 40 parts of
maltose (purified maltose, HAYASHIBARA), 27 parts of titanium oxide, and 3 parts
of red ferric oxide was used in place of the coating solution in Example 1 to provide
133.9 mg of orally disintegrating coated tablets having 3.9 mg of coating layers per
130 mg of tablets.
[0055]
Example 16
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 40 parts of
erythritol (NIKKEN CHEMICAL AND SYNTHETIC INDUSTRY CO., LTD.), 27
parts of titanium oxide, and 3 parts of red ferric oxide was used in place of the
coating solution in Example 1 to provide 133.9 mg of orally disintegrating coated
tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0056]
Example 17
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 35 parts of
lactose, 5 parts of glycerin, 27 parts of titanium oxide, and 3 parts of red ferric oxide
was used in place of the coating solution in Example 1 to provide 133.9 mg of orally

disintegrating coated tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0057]
Comparative Example 8
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of
hydroxypropylmethylcellulose (HPMC) (TC-5R, Shin-Etsu Chemical Co., Ltd.), 35
parts of lactose, 5 parts of glycerin, 27 parts of titanium oxide, and 3 parts of red
ferric oxide was used in place of the coating solution in Example 1 to provide 133.9
mg of orally disintegrating coated tablets having 3.9 mg of coating layers per 130 mg
of tablets.
[0058]
Example 18
Coating was carried out in the same manner except that a water dispersion
having a solid content of 10% by weight composed of 30 parts of PVA, 5 parts of
maltitol, 10 parts of lactitol, 25 parts of lactose, 27 parts of titanium oxide, and 3
parts of red ferric oxide was used in place of the coating solution in Example 1 to
provide 133.9 mg of orally disintegrating coated tablets having 3.9 mg of coating
layers per 130 mg of tablets.
[0059]
Example 19
A water dispersion having a solid content of 10% by weight composed of 30
parts of PVA, 5 parts of maltitol, 10 parts of lactitol, 25 parts of lactose, 27 parts of
titanium oxide, and 3 parts of red ferric oxide was prepared. Into a film coating
machine (DRC-200, Powrex Corporation), 200 g of Amlodin (registered trademark)
OD Tablets 2.5 mg (Dainippon Sumitomo Pharma Co., Ltd.) containing amlodipine
besylate as a drug were loaded, and the coating solution was sprayed thereonto to
provide 86.3 mg of orally disintegrating coated tablets having 1.3 mg of coating

layers per 85 mg of tablets.
[0060]
Comparative Example 9
A solid preparation was prepared by the method described in JP 54-28812 A
(Patent Document 2). Lactose (Pharmatose 200M, DMV) in an amount of 47.2
parts, microcrystalline cellulose (CEOLUS PH-101, Asahi Kasei Chemicals
Corporation) in an amount of 35.4 parts, and corn starch (W, Nihon Shokuhin Kako
Co., Ltd.) in an amount of 35.4 parts were weighed out and loaded into a stirring
granulator (NMG-3L, NARA MACHINERY CO., LTD.). The resultant was
granulated while adding thereto distilled water in which 1.2 parts of methyl cellulose
(SH-15, Shin-Etsu Chemical Co., Ltd.) was dissolved to produce granulated material.
The obtained granulated material and Comil (197S, Powrex Corporation) were used
to carry out a treatment to obtain sized granules. To 119.2 parts of the sized
granules, 0.8 parts of magnesium stearate (Taihei Chemical Industrial Co., Ltd.) was
added and mixed for five minutes. The granules obtained were made into tablets of
120 mg using a tableting machine (correctl9, KIKUSUI SEISAKUSHO LTD.)
(inner core).
Next, 200 g of these tablets were loaded into a film coating machine (DRC-200,
Powrex Corporation), and a solution in which 45.2 parts of PVA, 5.65 parts of liquid
paraffin (KOKUSAN CHEMICAL Co., Ltd.), 45.2 parts of mannitol, 1.69 parts of
Span80 (Wako Pure Chemical Industries, Ltd.), and 2.26 parts of Tween80 (KANTO
KAGAKU) were dispersed was sprayed thereonto to provide 123 mg of coated
tablets having 3 mg of coating layers per 120 mg of tablets.
[0061]
Reference Example 2
Mannitol (PEARLITOL 300DC) was weighed in an amount of 96.745 parts
by weight, sieved through Mesh with 1 mm openings, and loaded into a fluidized bed

granulator. Next, onto these granules, the spray solution obtained by dissolving
0.005 parts of nalfurafine hydrochloride and 0.1 parts of sodium thiosulfate hydrate
in distilled water was sprayed to produce granulated granules. Mannitol
(PEARLITOL 50C) was then weighed out in an amount of 25.9675 parts, sieved
through Mesh with 1 mm openings, and loaded into a stirring granulator (NMG-3L)
together with 6.5 parts of crospovidone. Subsequently, the resultant was granulated
while adding thereto distilled water in which 0.0325 parts of red ferric oxide was
dispersed to produce granulated material. The granulated granules produced with
the fluidized bed granulator and the granulated granules produced with the stirring
granulator were treated individually using Comil to obtain sized granules. To
129.35 parts of the sized granules, 0.65 parts of magnesium stearate (Taihei
Chemical Industrial Co., Ltd.) was added and mixed for five minutes. The granules
obtained were made into WR tablets of 130 mg using a tableting machine (Correct 19,
KIKUSUI SEISAKUSHO LTD.).
[0062]
Example 20
Thirty parts of PVA, 40 parts of lactose, 27 parts of titanium oxide, and 3
parts of red ferric oxide were dispersed in distilled water to prepare a coating
solution having a solid content of 10% by weight. Into a film coating machine, 200
g of the orally disintegrating tablets prepared in Reference Example 2 was loaded,
and the coating solution was sprayed thereonto to provide 133.9 mg of orally
disintegrating coated tablets having 3.9 mg of coating layers per 130 mg of tablets.
[0063]
Example 21
A coating solution was prepared in the same manner as in Example 20, and
the coating solution was sprayed onto 0.1 mg of Harnal (registered trademark) D
Tablets (Astellas Phama Inc.) containing tamsulosin hydrochloride as a drug to

provide 122.9 mg of orally disintegrating coated tablets having 3.7 mg of coating
layers per 119.2 mg of tablets.
[0064]
Example 22
A coating solution was prepared in the same manner as in Example 20, and
the coating solution was sprayed onto 10 mg of Gamofa (registered trademark) D
Tablets (Sandoz) containing famotidine as a drug to provide 131.6 mg of orally
disintegrating coated tablets having 3.6 mg of coating layers per 128.0 mg of tablets.
[0065]
Example 23
A coating solution was prepared in the same manner as in Example 20, and
the coating solution was sprayed onto 5 mg of Ebastel (registered trademark) OD
Tablets (Dainippon Sumitomo Pharma Co., Ltd.) containing ebastine as a drug to
provide 103.9 mg of orally disintegrating coated tablets having 2.9 mg of coating
layers per 101.0 mg of tablets.
[0066]
Example 24
A coating solution was prepared in the same manner as in Example 20, and
the coating solution was sprayed onto Takepron (registered trademark) OD Tablets
15 (Takeda Pharmaceutical Company Limited) containing lansoprazole as a drug to
provide 296.6 mg of orally disintegrating coated tablets having 13.0 mg of coating
layers per 283.6 mg of tablets.
[0067]
Example 25
A coating solution was prepared in the same manner as in Example 20, and
the coating solution was sprayed onto 0.2 mg of Voglibose OD Tablets "TOWA"
(Towa Pharmaceutical Co., Ltd.) containing voglibose as a drug to provide 137.4 mg

of orally disintegrating coated tablets having 1.8 mg of coating layers per 135.6 mg
of tablets.
[0068]
Example 26
A coating solution was prepared in the same manner as in Example 20, and
the coating solution was sprayed onto 0.25 mg of Lendormin (registered trademark)
D Tablets (Boehringer Ingelheim) containing brotizolam as a drug to provide 172.3
mg of orally disintegrating coated tablets having 4.9 mg of coating layers per 167.4
mg of tablets.
[0069]
Example 27
1. Measurement of Oral Disintegration Time
For the orally disintegrating coated tablets obtained in Examples 1 to 26,
Comparative Examples 1 to 6, Comparative Example 8, and Comparative Example 9,
oral disintegration time was measured in three subjects consisting of a healthy adult
male(s) and female(s). The time calculated by subtracting the oral disintegration
time of the inner core tablet from the oral disintegration time of the orally
disintegrating coated tablet was defined as the oral disintegration time of the coating
layer (Table 2).
2. Crack in Coating Layer under High Humidity
For the orally disintegrating coated tablets obtained in Examples 1 to 26,
Comparative Examples 1 to 6, Comparative Example 8, and Comparative Example 9,
the presence of cracks in the coating layer was evaluated by visually observing the
tablet after storing at 40°C and 75% RH for one day (Table 2).
3. Light Stability Testing
The inner core (Reference Example 1) used in Example 7 and the orally
disintegrating coated tablet of Example 7 were spread out on a Petri dish so that they

do not overlap, and irradiated with white fluorescent light (2000 Lux/hr, total
600,000 Lux), after which the stability was evaluated by measuring the percentage of
residual drug (%) by HPLC method under the following conditions (Table 3).
Column: Inertsil ODS-3 (inner diameter 3.0 mm x length 150 mm, particle size 5
µm)
Guard column: Cartridge column E (inner diameter 3.0 mm x length 10 mm, particle
size 5 µm)
Mobile phase: 25 mmol phosphate buffer (pH 4.5)/acetonitrile mixture (77.5:22.5)
(v/v)
Flow rate: 0.5 mL/min
Detection wavelength: 280 nm
4. Measurement of Tablet Hardness
The inner core (Reference Example 1) used in Example 7 and the orally
disintegrating coated tablet of Example 7 were measured using a hardness tester
(TABLET TESTER6D, Schleuniger) (Table 4).
5. Measurement of Friability
Friability of Amlodin (registered trademark) OD Tablets 2.5 mg and the
coated tablets of Amlodin (registered trademark) OD Tablets 2.5 mg obtained in
Example 19 were measured immediately after production and after storage under the
conditions of 40°C and 75% RH for two hours in accordance with the Friability Test
described in the Japanese Pharmacopoeia 15th Edition, General Notices, page F-131
(Table 5).

As shown in Table 2, it was shown that a stable orally disintegrating coated
tablet containing a drug, wherein the tablet is coated with a coating layer containing a
water-soluble substance and a polyvinyl alcohol resin of not less than 5% by weight
based on the weight of the coating layer, the water-soluble substance dissolving in an
amount of 1 g or more in less than 10 mL of water at 20°C, having a hydroxyl
group(s) in its molecule, and having a molecular weight of not more than 200 per a
unit hydroxyl group, has excellent orally disintegrating properties compared to the
formulations of Comparative Examples and at the same time does not cause a crack

in the coating layer even when stored under high-humidity conditions of 40°C and
75% RH. As shown in Table 3, it became apparent that a marked light stabilizing
effect is shown and even in the case of a light-unstable drug, sufficient stability can
be ensured when handling the medicament. Further, as shown in Table 4 and Table
5, the tablet hardness is enhanced and at the same time the friability is markedly
improved, and these effects allow single-dose packaging of the orally disintegrating
tablet which hitherto could not be packaged in a single-dose pack, which in turn
improves drug compliance of patients and enhances therapeutic effects.
INDUSTRIAL APPLICABILITY
[0077]
The present invention is applicable also to various drugs. Particularly, the
light-unstable drug to which it has hitherto been difficult to apply can be made into
an orally disintegrating tablet. In addition, the tablet hardness is enhanced and at
the same time the friability is markedly improved, and these effects allow single-dose
packaging of the orally disintegrating tablet which hitherto could not be packaged in
a single-dose pack, which in turn improves drug compliance of patients and enhances
therapeutic effects.

we claim:
1. A stable orally disintegrating coated tablet containing a drug, wherein said
tablet is coated with a coating layer containing a water-soluble substance and a
polyvinyl alcohol resin of not less than 5% by weight based on the weight of said
coating layer, said water-soluble substance dissolving in an amount of 1 g or more in
less than 10 mL of water at 20°C, having a hydroxyl group(s) in its molecule, and
having a molecular weight of not more than 200 per a unit hydroxyl group.
2. The stable orally disintegrating coated tablet according to claim 1, wherein
said water-soluble substance is at least one of saccharides, sugar alcohols, and
polyhydric alcohols.
3. The stable orally disintegrating coated tablet according to claim 1, wherein
said water-soluble substance is at least one of maltose, maltitol, sorbitol, xylitol,
glycerin, fructose, glucose, lactitol, isomaltose, lactose, erythritol, mannitol,
trehalose, sucrose, and polyethylene glycol having an average molecular weight of
not more than 400.
4. The stable orally disintegrating coated tablet according to claim 1, wherein
said polyvinyl alcohol resin in said coating layer has a content of 10 to 60% by
weight based on the weight of said coating layer.
5. The stable orally disintegrating coated tablet according to claim 1,
characterized in that weight ratio of said polyvinyl alcohol resin in said coating layer
to said water-soluble substance is 1:0.1 to 1:9.
6. The stable orally disintegrating coated tablet according to claim 1,
characterized in that said coating layer disintegrates in an oral cavity within 18
seconds and said orally disintegrating coated tablet disintegrates in an oral cavity
within 60 seconds.
7. The stable orally disintegrating coated tablet according to claim 1,
characterized in that said coating layer contains a light shading agent.

8. The stable orally disintegrating coated tablet according to claim 7, wherein
said light shading agent is at least one of titanium oxide, red ferric oxide, yellow
ferric oxide, black iron oxide, talc, and kaolin.
9. The stable orally disintegrating coated tablet according to claim 7,
characterized in that said light shading agent in said coating layer has a content of 0.1
to 40% by weight based on the weight of said coating layer.
10. The stable orally disintegrating coated tablet according to claim 1, wherein
said drug is at least one of nalfurafine, amlodipine, donepezil, ebastine, selegiline,
famotidine, irsogladine, brotizolam, olanzapine, lansoprazole, bepotastine,
ramosetron, tamsulosin, naftopidil, polaprezinc, voglibose, rizatriptan, midodrine,
risperidone, ondansetron, loratadine, montelukast, azulene sulfonate, etizolam,
enalapril, captopril, glibenclamide, chlormadinone acetate, doxazosin, triazolam,
domperidone, ketotifen, bromperidol, pravastatin, simvastatin, loperamide, lisinopril,
rilmazafone, precipitated calcium carbonate, magnesium oxide, mecobalamin,
alfacalcidol, bromocriptine, and pramipexole, and pharmaceutically acceptable salts
and solvates thereof.

The present invention relates to a stable orally disintegrating coated tablet
containing a drug, wherein the tablet is coated with a coating layer containing a
water-soluble substance and a polyvinyl alcohol resin of not less than 5% by weight
based on the weight of the coating layer, the water-soluble substance dissolving in an
amount of 1 g or more in less than 10 mL of water at 20°C, having a hydroxyl
group(s) in its molecule, and having a molecular weight of not more than 200 per a
unit hydroxyl group. There is provided a stable orally disintegrating coated tablet
which does not cause a crack in the coating layer even when the orally disintegrating
tablet has been swollen by moisture absorption under high humidity, while ensuring
rapid disintegration properties in an oral cavity. In the case of an orally
disintegrating tablet containing a light-unstable drug, degradation of the drug can be
suppressed by blending a light shading agent in the coating layer.