BASIS PARTICLES, METHOD FOR MANUFACTURING THE SAME, AND
ORALLY-DISINTEGRATING TABLET
BACKGROUND OF THE INVENTION
[0001]
1. Field of the Invention
The present invention relates to basis particles, a method for manufacturing
the same, and orally-disintegrating tablets, and more specifically relates to basis
particles capable of masking bitterness, a method for manufacturing the same, and
orally-disintegrating tablets.
[0002]
2. Description of Related Art
The dosage form most generally adopted in oral solid preparations is the tablet
form. Conventional pharmaceutical preparations disintegrate in the digestive tract
such as stomach, if they are swallowed soon after ingestion since they disintegrate after
two minutes or more.
However, orally-disintegrating tablets, which are easily swallowed by the
young and elderly, that is, emphasize increasing patient quality of life (QOL), are noted
as a dosage form that may cause an unpleasant sensation due to the bitterness of a basis
(i.e., a main ingredient or an active drug) at the time of ingestion as they disintegrate
intraorally within 30 seconds of ingestion, although they can be ingested without water.
[0003]
The development of technology that makes it easier for a basis to be absorbed
by the stomach or intestines and technology for masking the bitter taste of the basis has
therefore been taking place. As the simplest of these methods, technology to conceal
the bitterness by the addition of sweetners such as aspartame, stevia, or sugar alchohol
and the addition of a flavoring such as L-menthol is proposed (see, for example,
Japanese Laid-Open Patent Application H8-208517, H10-101582, 2001-302510 and

2001-106639).
[0004]
However, since this technology conceals the bitterness with other flavors,
complete elimination of drug bitterness is difficult.
Technology where the basis is coated with a coating agent has therefore been
proposed (see, for example, Japanese Laid-Open Patent Application 2005-60309).
With this technology, it is disclosed that bitterness is suppressed by directly coating the
basis with a water-insoluble coating film.
[0005]
However, with this technology, delays in elution are observed depending on
the drug, and a phenomenon may occur where the amount of drug originally included is
not eluted. When this tendency is observed in elution tests, elution occurs without
problems in the case of a basic drug in an eluate at an acidic pH but delays in elution
occur with an eluate of a pH of 5.0 or more.
[0006]
When coated pharmaceutical preparations are ingested in cases where the pH
within the stomach is high as a result of achlorhydria or diet, elution of the drug is
insufficient and satisfactory results cannot be obtained.
SUMMARY OF THE INVENTION
[0007]
It is an object of the present invention to provide a basis (i.e., a main
ingredient or an active drug) particles and method for manufacturing the same as well as
an orally-disintegrating tablet with which superior elution can be exhibited without
dependence on bodily pH and despite characteristics of the acidic and basic basis, and
the bitterness of the basis can be masked.
[0008]

The present invention provides a basis particle comprising a basic or acidic
basis particle coated by a water-insoluble coating film, wherein the water-insoluble
coating film contains a substance that is acidic with respect to the basic basis or basic
with respect to the acidic basis.
Further, the present invention provides a method for manufacturing a basis
particle comprising: coating a basic or acidic basis particle with a water-soluble primary
coating film containing a substance that is acidic with respect to the basic basis or basic
with respect to the acidic basis, and coating the basis particle obtained with a
water-insoluble coating film.
Moreover, the present invention provides an orally-disintegrating tablet
comprising the basis particle of the above, wherein the tablet is tabletted with a
pharmaceutically acceptable excipient, disintegrant and/or lubricant.
[0009]
According to the basis particles and method for manufacturing the basis (i.e., a
main ingredient or an active drug) particles of the present invention, it is possible to
temporarily adjust pH occurring in the immediate proximity of the basis particles by
using a coating film, elution of the basis particles is suppressed and superior elution is
exhibited without dependence on bodily pH. It is also possible to mask tastes such as
the bitterness of the basis and it is possible to ingest drugs without sensing any
bitterness.
[0010]
According to orally-disintegrating tablets of the present invention, it is
possible to provide pharmaceutical preparations without fear of affecting the therapeutic
effects even in achlorhydric patients or when the drug is ingested postprandially.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011]
FIGs. 1A and 1B are graphs showing a drug elution behavior of the basis

particles and the orally-disintegrating tablet of the present invention, respectively;
FIGs. 2 A and 2B are graphs showing a drug elution behavior of the basis
particles and the orally-disintegrating tablet of the comparative example, respectively.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0012]
The present invention is constructed to comprise a basis particle and a
water-insoluble coating film coating at least the basis particle.
There is no particular restriction on the basis particles used in the present
invention, but it can be the basis particles themselves having basic or acidic property.
Examples includes medicines for airsickness, analgesic antipyretic, aromatic stomachic,
digestant, antacid agent, vitamin, nutrient tonic, enzyme preparation, nutrient tonic
supplement, anti-inflammatory, antirheumatic drug, gout remedy, antihistamine, allergy
agent, antibiotic agent, synthetic antibacterial, medicine for dental and oral use,
bronchodilator, cough remedy, expectorant drug, sleep sedative, anxiolytic agent,
antiepileptic drug, psychoneurotic agent, autonomic agent, central nervous system drug,
antispasmodic agent, ameliorant of cerebral metabolism, ameliorant of cerebral
circulation, antiParkinson's disease agent, Alzheimer therapeutic agent, cardiotonic
agent, antiarrhythmia agent, diuretic agent, vasoconstrictor, vasodilatation agent,
hypotensive agent, antihyperlipemia agent, constipating agent, peptic ulcer agent,
cathartic, hormone agent, diabetes agent, and the like, as well as prodrugs.
[0013]
In particular, examples of the basic basis include substances having, for
example, an amino group (primary, secondary, tertiary, or quaternary), nifedipine,
nitrendipine, amlodipine besilate, risperidone, zolpidem tartrate, donepezil
hydrochloride, diclofenac sodium, loxoprofen sodium, ibuprofen, and the like.
Examples of the acidic basis include acetaminophen, ascorbic acid, and the like. These

can also be in the form of a salt such as a free base, a hydrochloride, and a
sulfate.[0014]
From a different viewpoint, the basis can be drug having bitterness. Example
of the basis having bitterness include nifedipine, nitrendipine, amlodipine besilate,
risperidone, zolpidem tartrate, donepezil hydrochloride, diclofenac sodium, loxoprofen
sodium, ibuprofen, acetaminophen, and the like. The basis particles of the present
invention are therefore particularly useful for the basic basis because a bitter drug tends
to have basicity.
[0015]
The basis can be powdered, solid, granular, and the like. There are no
particular restrictions with regards to size, and the size can, for example, be varied as
appropriate taking texture etc. into consideration when ingesting as an
orally-disintegrating tablet. Specifically, a mean particle diameter of about 5 μm to
about 50 μm may be shown as an example. A method of arranging particle diameters
using, for example, a sieve or a membrane filter etc., or a method of crushing using a
ball mill pulverizer, hammer mill pulverizer, or pin mill pulverizer etc. can be given as
methods for making the basis an appropriate shape and size. The basis can also be
granulated using a known method in the field.
[0016]
As the water-insoluble coating film for coating the basis particles, any of the
various water-insoluble coating film which is commonly used in the field can be used.
Here, as defined by the Japanese Pharmacopoeia, "water-insoluble" means extremely
difficult to dissolve (the quantity of solvent required to dissolve 1g of solute is from
1000 ml or more to less than 10000 ml) and hardly dissolves at all (10000 ml or more).
There is no particular restriction on the coating agent for forming the water-insoluble
coating film, it can be used, for example, ethylcellulose, methacrylic acid co-polymer,
amino methacrylic acid methacrylate co-polymer, hydroxypropylmethylcellulose
phthalate, and the like. These can be used alone or as mixture of two or more.

There is no particular restriction on the film thickness of the water-insoluble
coating film, for example, about 0.01 μm to about 20 urn. Further, from a further
point of view, the water-insoluble coating film is preferably formed so as to be an extent
of about 15 % to about 80% by weight with respect to the whole weight of the basis
particles. It is therefore appropriate for a mean particle diameter of the basis particles
of the present invention coated by the water-insoluble coating film to be varied between,
for example, about 50 μm to about 300 μm, and preferably about 50 μm to about 200
An acidic substance with respect to the basic basis, or a basic substance with
respect to an acidic basis is included at an inner part of the water-insoluble coating film,
in other words, on the inside of the coating film. This means that the basis and the
basic or acidic substance are present together at the space coated by the water-insoluble
coating film.
[0018]
It is therefore preferable that a substance that does not affect the effectiveness
of the basis is adopted as the basic or acidic substance such as, for example, a substance
used as a pH adjuster. Examples of the acidic substance include, for example, an
organic acid such as citric acid, fumaric acid, succinic acid, acetic acid, tartaric acid, or
salts thereof, and an inorganic acid such as hydrochloric acid, sulfuric acid,
hydrobromic acid, phosphoric acid or salts thereof. Among these, it is preferably citric
acid, acetic acid, tartaric acid, or salts thereof as the acidic substance. Examples of the
basic substance include, for example, sodium hydroxide, sodium carbonate, sodium
hydrogencarbonate, ammonia, and the like. These can be used alone or as mixture of
two or more.
[0019]
The quantity of the basic or acidic substance contained in the water-insoluble
coating film can be varied appropriately according to the kind of basis, the kind of the

basic or acidic substance, etc., and, for example, about 0.1 % to about 20 % by weight
with respect to the total weight of the basis particles is appropriate. By adjusting this
range, at the space enclosed within the water-insoluble coating film, it is possible to
adjust the pH of the basis appropriately using slight permeation of fluid in the initial
stage. The basis is therefore eluted in an appropriate manner under an environment
such as in the stomach, intestines, and the like.
[0020]
The specific form of the basic or acidic substance being contained within
(inside) the water-insoluble coating film may refer to existing between the basis
particles and the water-insoluble coating film, being mixed with the basis particles, or
the like.
More specifically, an example form is shown where, within the
water-insoluble coating film, the basis particles are coated by a water-soluble primary
coating film, and the water-soluble primary coating film includes the acidic substance
with respect to the basic basis, or basic substance with respect to the acidic basis.
[0021]
As the water-soluble primary coating film, any of the various water-soluble
coating film which is commonly used in the field can be used. Here, as defined by the
Japanese Pharmacopoeia, "water-soluble" means moderately-soluble (the quantity of
solvent required to dissolve 1g of solute is from 10 ml or more to less than 30 ml),
easily-soluble (from 1 ml or more to less than 10 ml) and extremely easily-soluble (less
than 1 ml). The water- soluble primary coating film may include a film which is
caused to swell by water and also results in a clear or slightly cloudy fluid having
consistency as with hydroxypropyl methylcellulose described later. There is no
particular restriction on a coating agent for forming the water-soluble primary coating
film, but examples include hydroxypropylmethylcellulose, methylcellulose,
hydroxypropyl cellulose, and the like, for example. These can be used alone or as
mixture of two or more.

There is no particular restriction on the film thickness of the water-soluble
primary coating film, but it is suitably about 0.01 jam to about 20 (am, for example.
Further, from a further point of view, the water-soluble primary coating film is
preferably formed so as to an extent of about 3 % to about 15% by weight with respect
to the whole weight of the basis particles.
The amount of the basic or acidic substance contained in the water-soluble
primary coating film can be, for example, provided of 1 % to 30 % by weight (not
including water) with respect to the total weight of the water-soluble primary coating
film.
In a further form, when a mixture of the basis particles and the acidic or basic
substance exists within the water-insoluble coating film, as described above, the
granulated or ungranulated acidic or basic substance can exist together with the
granulated or ungranulated basis particles, or the basis and acidic or basic substance can
be mixed together and granulated to form a granules.
[0023]
The granules can be formed using a known method in the field such as, for
example, wet granulation and dry granulation, optionally, together with an additive for
granulation. For example, granulation can be performed using various apparatus for
wet granulation such as a fluidized bed granulation dehydrator, an aggregate granulating
machine, a cylindrical extrusion aggregating machine, and a roll fluidized bed
granulated coating machine, or various apparatus for dry granulation using spray dry
techniques such as dry granulation machines, e.g., roller compactors, and slag tablet
machines.
[0024]
In a method for manufacturing a basis particles of the present invention, first,
a basis particles are coated with a water-soluble primary coating film containing an

acidic substance with respect to a basic basis, or a basic substance with respect to an
acidic basis.
Any known method in the field can be utilized as the method for coating the
basis particles with the water-soluble primary coating film. Particularly, a coating
agent constituting the water-soluble primary coating film may be dissolved in a solvent
such as water, and then, the basis particles may be coated with the water-soluble
primary coating film using by a known method such as pan coating, flow coating, and
rolling coating utilizing apparatus such as an inclined type pan, an aeration type rotating
cylinder coating apparatus, a general purpose flow coating apparatus, a Worcester-type
coating apparatus, and a composite rolling/flow coating apparatus. Also, it may be
utilized a pump, a squirt gun, a solution sending line, and the like.
[0025]
The coating agent may optionally includes a known additives in the field, such
as a plasticizer, a sweetener, a dispersion stabilizer, an excipient, lubricant, and the like.
Examples of the plasticizer include triethyl citrate, triacetin, ziacetin,
acetylated monoglyceride, dibutyl sebacate, medium-chain triglyceride, dibutyl adipate,
and the like.
Examples of the dispersion stabilizer include sodium polyphosphate, trisodium
citrate, and the like.
As the sweetener, excipient, lubricant, and the like can be used the same
agents as described bellow.
[0026]
Next, the particles coated with the water-soluble primary coating film are
coated with the water-insoluble coating film.
Any known method in the field can be utilized as the method for coating the
basis particles obtained with the water-insoluble coating film. For example, the same
method as the covering method described above other than using an organic solvent can
also be given.

Basis particles obtained in this way can then be made into a pharmaceutical
preparation in various ways. For example, other forms such as tablet,
orally-disintegrating tablet, capsule, pill, troche, granule, powder, suspension, emulsion,
liquid, syrup, ant the like provided orally are also possible. Among these, tablet form,
particularly orally-disintegrating tablet, is useful.
[0028]
These pharmaceutical preparations, particularly orally-disintegrating tablets,
can be made by tableting together with commonly used additives.
Examples of the additive include excipient, disintegrating agent, lubricant,
binder, solubilizing agent, fluidiser, sweetener, fragrance, foaming agent, surfactant,
preservative, coloring agent, and the like.
Examples of the excipient include glucose, fructose, lactose, sucrose,
hydrogenated maltose, sugar alcohol (for example, D-mannitol, erythritol, sorbitol,
xylitol, trehalose, maltitol, lactitol, etc.), and the like. These can be used alone or as
mixture of two or more.
[0029]
Examples of the disintegrating agent include crospovidone, sodium starch
glycolate, sodium carboxymethyl starch, starch, partially pregelatinized starch,
cornstarch, lactose, calcium carbonate, precipitated calcium carbonate, calcium citrate,
light silicic anhydride, synthetic aluminum silicate crystalline cellulose, low substitution
degree hydroxypropylcellulose, croscarmellose, sodium croscarmellose, calcium
carboxymethylcellulose, carmellose, hydroxypropyl starch, and the like. These can be
used alone or as mixture of two or more. Among these, it is preperably croscarmellose,
sodium starch glycolate, carmellose, starch, hydroxypropyl starch, crospovidone, and
the like. The amount of the disintegrating agent can be, for example, provided of
about 0.1 % or more, preferably about 0.5 % or more, and more preferably about 2 % or
more by weight with respect to the total weight of the orally-disintegrating tablet.

Also, it can be included about 30 % or less, preferably about 25 % or less, and more
preferably about 15 % by weight.
[0030]
Examples of the lubricant include magnesium stearate, calcium stearate, talc,
sucrose fatty acid ester, polyethyleneglycol, stearic acid, light silicic anhydride,
hydrogenated rape oil, hydrogenated castor oil, glycerin fatty acid ester, sodium stearyl
fumarate, sodium benzoate, L-leucin, L-valine, and the like. These can be used alone
or as mixture of two or more.
[0031]
Examples of the binder include a water-soluble substance such as gelatine,
agar, alginic acid, sodium alginate, dextrin, xanthan gum, arabian gum,
hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose,
polyvinylpyrrolidone, partially saponification polyvinyl alcohol, methylcellulose,
pullulan, partially pregelatinized starch, sugar, and the like. These can be used alone
or as mixture of two or more.
[0032]
Examples of the solubilizing agent include magnesium oxide, calcium oxide,
sodium citrate, magnesium chloride, sodium carbonate, sodium bicarbonate, and the
like. These can be used alone or as mixture of two or more.
Examples of the fluidizer include hydrated silicon dioxide, light silicic
anhydride, and the like.
Examples of the sweetener include aspartame, sodium saccharin, dipotassium
glycyrrhizinate, stevia, thaumatin, and the like. These can be used alone or as mixture
of two or more.
[0033]
Examples of the fragrance include mint, lemon or orange extract, and the like.
Examples of the foaming agent include tartrate, citrate, bicarbonate, and the
like.

Examples of the surfactant include an anionic surfactant such as sodium
alkylsulfate; a nonionic surfactant such as sucrose fatty acid ester, polyoxyethylene
sorbitan fatty acid ester, polyoxyethylene fatty acid ester and polyoxyethylene castor oil
derivatives, and the like. These can be used alone or as mixture of two or more.
[0034]
Examples of the preservative include benzoic acid, parahydroxybenzoic acid,
and the like or a salt thereof.
Examples of the coloring agent include yellow oxide of iron, yellow iron
sesquioxide, iron sesquioxide (red), orange essence, brown iron oxide, caramel, light
silicic anhydride, Food Blue No.5, Food Yellow No.4, Food Yellow No.4 aluminum
lake, Food Yellow No.5, Food Red No.2 (Amaranth), Food Red No.3, Food Red
No. 102, talc, sodium tetrafluorescein, green tea powder, Vitamin C, and the like.
[0035]
The tableting can be carried out using a known apparatus employing a known
method in the field. For example, a hydraulic hand press machine, a single punch
tableting machine, a rotary type tableting machine, which are provided with a tableting
mill, upper and lower pestles for tableting, and the like can be utilized as apparatus for
tableting and compression molding.
[0036]
Tableting requires regulation so that the tablets obtained have the appropriate
hardness and rapidly disintegrate as orally-disintegrating tablets. There is no particular
restriction on the tablet compression pressure, but it can be adjusted appropriately
according to the apparatus used, the theory, the size of the tablets, and the type of basis,
etc. In the case of using the apparatus described above, for example, a tablet
compression pressure is suitably about 50kg/cm or more, and about 1500 kg/cm or
less, preferably about 300 kg/cm2 or more, and 1000 kg/cm2 or less.
[0037]

There is no particular restriction on the shape of the orally-disintegrating tablet
of the present invention, but it includes a disc-shaped, a donut shaped, a polygonal
plate-shaped, a spherical, an ellipsoidal, a caplet-shaped, and the like. It is preferable
for the shape of the tablets to be the common disc-shape. There is no particular
restriction on the size, but it is preferably a slightly larger size to the extent that
swallowing does not take place directly, for example, a diameter of about 3 mm to about
30mm, and a thickness of about 1 mm to about 10mm.
[0038]
The following is a description of an example of basis particles, a method for
manufacturing basis particles, and orally-disintegrating tablets of the present invention.
Example 1
5.3g of hydroxypropyl methylcellulose, 0.96g of citric acid anhydride, and
0.53g of polyethelene glycol (PEG-6000) was dissolved in 73.21g of purified water to
give a coating fluid I.
9.12g of triacetin was added to 121.5g of 30 % ethylcellulose dispersion fluid
(CX-1), the obtained mixture was stirred for dispersion by agitation. And then, 2.44g
of D-mannitol and 106.94g of purified water was added to the mixture, and stirred for
dispersion to give a coating fluid II.
[0039]
300g of blended powder of zolpidem tartrate: D-mannitol at a ratio of 1:1 was
introduced into Worcester-type fluid bed granulating machine (MP-SPC-01, Burridge
Engineering), and coating was performed firstly under the conditions of an intake air
temperature of 75 degrees centigrade, an intake air flow of 0.40 m3/sec, an atomized air
flow of 15.0 to 22.5 NL/minute, and a spray velocity for the coating fluid I of 4.5 to 7.8
g/minute.
And then, another coating was performed under the conditions of an intake air
temperature of 75 degrees centigrade, an intake air flow of 0.35 m3/sec, an atomized air

flow of 17.5 NL/minute, and a spray velocity for the coating fluid II of 6.0 to 8.0
g/minute to give basis particles I having a mean particle diameter of 150 urn.
[0040]
24 g of the basis particles 1,20 g of microcrystalline cellulose, 5 g of
anhydrous calcium hydrogen phosphate, 25 g of D-mannitol, 14 g of mannitol for direct
impacting (PARTECH 100M, Merck Pharmaceuticals, granulated mannitol, mean
granule diameter 90 to 120 jam), 10 g of crospovidone, 1 g of aspartame, and 1 g of
magnesium stearate warer mixed together. Tableting was then carried out at a rotary
tableting machine to give 100 mg tablets of a hardness of 40 N constituting
orally-disintegrating tablets that disintegrate in twenty seconds within the mouth.
[0041]
Comparative Example 1
11.43 g of triacetin was added to 152.4 g of 30 % ethylcellulose dispersion
fluid (CX-1), the obtained mixture was stirred for dispersion by agitation. And then,
2.85 g of D-mannitol and 133.32 g of purified water was added to the mixture, and
stirred for dispersion to give a coating fluid.
300g of blended powder of zolpidem tartrate: D-mannitol at a ratio of 1:1 was
introduced into Worcester-type fluid bed granulating machine (MP-SPC-01, Burridge
Engineering), and coating was performed under the conditions of an intake air
temperature of 75 degrees centigrade, an intake air flow of 0.35 m3/sec, an atomized air
flow of 17.5 NL/minute, and a spray velocity for the coating fluid of 6.0 to 8.0 g/minute
to give basis particles II having a mean particle diameter of 112 μm.
[0042]
Test Example 1
Elution test according to the rules for elution test of the Japanese
Pharmacopoeia were then carried out for the basis particles I obtained in the Example 1
and the orally-disintegrating tablet made using the basis particles I. The test solutions
were of pH1.2, pH5.0, and water. The results are shown in FIG. 1A and FIG. IB. In

FIG. 1A and FIG. 1B, the black circles denote a test solution of pH 1.2, the black
triangles denote a test solution of pH 5.0, and the black squares denote water.
According to FIG. 1, it is observed that the basis particles of the present
invention elute sufficiently in test solutions whatever the pH, and this does not depend
on the pH. Further, rapid elution is confirmed regardless of the pH for tablet that
disintegrate within the mouth. Bitterness is also suppressed sufficiently when the
orally-disintegrating tablets disintegrate within the mouth.
[0043]
Test Example 2
Elution test according to the rules for elution test of the Japanese
Pharmacopoeia were then carried out for the basis particles II obtained in the
Comparative Example 1 and the orally-disintegrating table made using the basis
particles II. The test solutions are of pH1.2, pH5.0, and water. The results are shown
in FIG. 2A and FIG. 2B.
According to FIG. 2, it is observed that there is a striking delay in elution for
the basis particles II when the pH is high at pH 5.0 and in water. Similarly, a striking
delay in elution can also be observed for a high pH of 5.0 and for water for the
orally-disintegrating table.
[0043]
The present invention can be utilized in various pharmaceutical drug
preparations in order to conceal any taste or flavor, not just bitterness. Further, it is
also possible to use any pharmaceutical drug preparation with the intent of adjusting
solubility with respect to a basic or acidic drug.
[0044]
This application claims priority to Japanese Patent Application No. 2007-104477.
The entire disclosure of Japanese Patent Application No. 2007-104477 are hereby
incorporated herein by reference.
While only selected embodiments have been chosen to illustrate the present

invention, it will be apparent to those skilled in the art from this disclosure that various
changes and modifications can be made herein without departing from the scope of the
invention as defined in the appended claims. Furthermore, the foregoing description
of the embodiments according to the present invention is provided for illustration only,
and not for the purpose of limiting the invention as defined by the appended claims and
their equivalents.

What is claimed is:
1. A basis particle comprising a basic or acidic basis particle coated by a
water-insoluble coating film,
wherein the water-insoluble coating film contains a substance that is acidic
with respect to the basic basis or basic with respect to the acidic basis.
2. The basis particle according to claim 1, wherein the basic or acidic basis
particle is primary coated by a water-soluble primary coating film inside of the
water-insoluble coating film, and the substance that is acidic with respect to the basic
basis or is basic with respect to the acidic basis is included in the water-soluble primary
coating film.
3. The basis particle according to claim 1, wherein the water-insoluble
coating film is formed by at least one compound selected from the group consisting of
ethylcellulose, methacrylic acid co-polymer, amino methacrylic acid methacrylate
co-polymer and hydroxypropylmethylcellulose phthalate.
4. The basis particle according to claim 1, wherein the basis particle is the
basic basis particle, and the acidic substance is at least one compound selected from the
group consisting of citric acid, acetic acid, tartaric acid and a salt thereof.
5. The basis particle according to claim 1, wherein the water-soluble primary
coating film is formed by at least one compound selected from the group consisting of
hydroxypropylmethylcellulose, methylcellulose and hydroxypropyl cellulose.
6. A method for manufacturing a basis particle comprising:

coating a basic or acidic basis particle with a water-soluble primary coating
film containing a substance that is acidic with respect to the basic basis or basic with
respect to the acidic basis, and
coating the basis particle obtained with a water-insoluble coating film.
7. An orally-disintegrating tablet comprising the basis particle of Claim 1,
wherein the tablet is tabletted with a pharmaceutically acceptable excipient, disintegrant
and/or lubricant.

A basis particle comprises a basic or acidic basis particle coated by a water-insoluble coating film, wherein the water-insoluble coating film contains a substance that is acidic with respect to the basic basis or basic with respect to the acidic basis. According to the basis particles (i.e., a main ingredient or an active drug)of the present invention, it is possible to temporarily adjust pH occurring in the immediate proximity of the basis particles by using a coating film, elution of the basis particles is suppressed and superior elution is exhibited without dependence on bodily pH. It is
also possible to mask tastes such as the bitterness of the basis and it is possible to ingest drugs without sensing any bitterness.