[DESCRIPTION]
CONTROLLED-RELEASE MICROPARTICLES AND METHOD OF
PREPARING SAME
[Technical Field]
The present disclosure relates to a controlled-release microparticle including
a matrix comprising a pharmacologically active component, and a method for
preparing the same.
[Background Art]
Many pharmacologically active substances including drugs and prodrugs are
prepared into orally administrable preparations allowing controlled release (also
known as slow release or sustained release).
When such a drug as tamsulosin hydrochloride is administered in the form of
a controlled-release tablet, increase of blood level and concentration-dependent side
effects resulting therefrom occur frequently because of its nonuniform rate of passing
through the pyloric sphincter. Thus, there have been attempts to prepare a tablet
with a small particle diameter that is disintegrated quickly in the buccal cavity.
For instance, Korean Patent No. 0530546 discloses a composition for a tablet
comprising drug-containing controlled-release microparticles of 350 um or smaller, an
excipient and a binder. However, the patent relates to controlled-release
microparticles without a matrix comprising a drug. The disclosed controlled-release

microparticles are disadvantageous in that control of drug release is difficult, a large
amount of coating substance is required to achieve controlled release of the
microparticles, and a long coating time is required.
[Disclosure]
[Technical Problem]
The present disclosure is directed to providing a controlled-release
microparticle allowing easy control of drug release.
The present disclosure is also directed to providing a method for preparing a
controlled-release microparticle allowing easy control of drug release.
[Technical Solution]
In one general aspect, the present disclosure provides a controlled-release
microparticle including: a matrix comprising a pharmacologically active component;
and a controlled-release layer comprising a substance which forms a
controlled-release stratum on the matrix. The pharmacologically active component
may be uniformly dispersed or distributed in the matrix.
In another general aspect, the present disclosure provides a method for
preparing a controlled-release microparticle, including: preparing a matrix comprising
a pharmacologically active component; and forming a controlled-release layer
comprising a substance which forms a controlled-release stratum on the matrix.
[Advantageous Effects]

The controlled-release microparticle of the present disclosure not only allows
effective release control of a drug but can also exhibit outstanding dissolution
characteristics even when a small amount of coating substance is used.
[Description of Drawings]
Figure 1 shows a dissolution test result of controlled-release microparticles
prepared in Example 5 and Comparative Example 1.
[Mode for Invention]
The present disclosure provides a dual controlled-release system comprising:
a matrix comprising a pharmacologically active component; and a controlled-release
layer comprising a substance which forms a controlled-release stratum on the matrix.
The matrix allows primary controlled release of the active component, and the
additional coating layer allows secondary controlled release of the active component.
The amount of the coating substance and coating time can be reduced remarkably.
Consequently, comparable or better dissolution characteristics can be exhibited even
when a smaller amount of coating substance is used.
In an embodiment, the substance which forms a controlled-release stratum
may be a polymer selected from a group consisting of a water-insoluble polymer, a
gastric-soluble polymer, an enteric-soluble polymer, a water-soluble polymer, and a
mixture thereof. The polymer material may be selected adequately depending on
purposes.
The substance which forms a controlled-release stratum may be a
pH-independent water-insoluble polymer for enabling controlled drug release. For

example, the water-insoluble polymer may be one or more selected from a group
consisting of a ethyl cellulose, water-insoluble cellulose ether such as Aquacoat
(FMC), etc., an ethyl acrylate-methyl methacrylate-chlorotrimethylammoniumethyl
methacrylate copolymer (e.g., Eudragit RS, Evonik), polyvinyl acetate, an ethyl
acrylate-methyl methacrylate copolymer, and a dispersion thereof (As an example of
the ethyl acrylate-methyl methacrylate copolymer dispersion, Eudragit NE30D
(Evonik) may be used.).
For example, the gastric-soluble polymer may be one or more selected from a
group consisting of polyvinyl acetal diethylamino acetate, and a methyl
methacrylate-butyl methacrylate-dimethylaminoethyl methacrylate copolymer (e.g.,
Eudragit E, Evonik).
The substance which forms a controlled-release stratum may be an
enteric-soluble polymer for providing enteric solubility. For example, the
enteric-soluble polymer may be one or more selected from a group consisting of
hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose
phthalate, hydroxymethylethyl cellulose phthalate, carboxymethylethyl cellulose, a
methacrylic acid-methyl methacrylate copolymer (e.g., Eudragit L100 and Eudragit S,
Evonik), and a methacrylic acid-ethyl acrylate copolymer (e.g., Eudragit L100-55 and
Eudragit L30D55, Evonik).
For example, the water-soluble polymer may be one or more selected from a
group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose,
polyvinylpyrrolidone, and polyvinyl alcohol.
These polymer materials may be used alone or in combination to attain
desired controlled release.
In an embodiment, the controlled-release layer may account for 15-60 wt%,

more specifically 20-40 wt%, based on the total weight of the controlled-release
microparticle. Within the aforesaid range, drug release may be effectively controlled
and coating may be accomplished in short time.
The active component may be uniformly dispersed or distributed in the matrix.
The active component may be any therapeutically or prophylactically active
component requiring controlled release, without particular limitation.
For example, the active component may be selected from a group consisting
of: an antidiabetic selected from a group consisting of acetohexamide, insulin,
tolbutamide, desmopressin, and glipizide; a diuretic selected from a group consisting
of hydrochlorothiazide, polythiazide, and triamterene; a bronchodilator selected from
a group consisting of aminopyrine, formoterol maleate, and theophylline; an
antitussive selected from a group consisting of codeine phosphate, noscapine,
dimemorfan phosphate, and dextromethorphan; an antiarrhythmic agent selected
from a group consisting of quinidine nitrate, digitoxin, propafenone hydrochloride, and
procainamide; a topical anesthetic selected from a group consisting of ethyl
aminobenzoate, lidocaine, and dibucaine hydrochloride; an antiepileptic selected
from a group consisting of phenytoin, ethosuximide, and primidone; a synthetic
adrenocortical steroid selected from a group consisting of hydrocortisone,
prednisolone, triamcinolone, and betamethasone; a peptic ulcer drug selected from a
group consisting of famotidine, ranitidine hydrochloride, cimetidine, sucralfate,
sulpiride, teprenone, plaunotol, 5-aminosalicylic acid, sulfasalazine, omeprazole,
pantoprazole, and lansoprazole; a central nervous system drug selected from a group
consisting of indeloxazine, idebenone, tiapride hydrochloride, bifemelane
hydrochloride, and calcium homopantothenate; an antihyperlipidemic agent selected
from a group consisting of pravastatin sodium, simvastatin, lovastatin, fluvastatin, and

atorvastatin; an antibiotic selected from a group consisting of phthalylampiciilin
hydrochloride, cefotetan, and josamycin; a benign prostatic hypertrophy therapeutic
agent selected from a group consisting of tamsulosin hydrochloride, doxazosin
mesylate, and terazosin hydrochloride; an antiasthmatic agent selected from a group
consisting of pranlukast, the philcast, albuterol, ambroxol, budesonide, and
levalbuterol; a gastroprokinetic agent selected from a group consisting of mosapride,
mosapride citrate, itopride, itopride hydrochloride, cisapride, cisapride monohydrate,
cisapride tartrate, domperidone, domperidone maleate, metoclopramide,
metoclopramide hydrochloride, trimebutine, trimebutine maleate, clebopride,
clebopride maleate, bromopride, and levosulpiride; an anti-depressant; a peripheral
circulation improving agent; an antithrombotic agent; an antihypertensive; a heart
failure drug; a diabetic complication drug; a skin ulcer drug; and a combination
thereof.
In the matrix, the active component may exist alone or in combination of two
or more. The active component may be present in any therapeutically effective
amount without particular restriction. For example, the active component may be
present in the matrix in an amount of 1-80 wt%, specifically 5-30 wt%, based on the
total weight of the matrix.
In a specific embodiment, the matrix may comprise an excipient and a binder.
The excipient included in the matrix is not particularly restricted as long as it
has properties appropriate for the formation of the matrix, and may be selected
adequately depending on purposes. For example, the excipient may be selected
from a group consisting of an organic excipient such as a cellulose derivative and a
saccharide, an inorganic excipient such as calcium phosphate, and a mixture thereof.
The cellulose derivative may be selected from a group consisting of microcrystalline

cellulose and low-substituted hydroxypropyl cellulose, the saccharide may be
selected from a group consisting of lactose, starch and pregelatinized starch, and the
calcium phosphate may be one or more selected from a group consisting of
anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, and
tricalcium phosphate.
The amount of the excipient in the matrix may be controlled adequately
depending on the dose of the drug and/or the final size of the microparticle. It may
be present in an amount of 20-99 wt%, specifically 70-95 wt%, based on the matrix.
Within the aforesaid range, drug release can be controlled effectively only with the
matrix.
The binder included in the matrix is not particularly restricted as long as it acts
as a binder for preparation of the microparticle. For example, the binder may be one
or more selected from water, an aqueous suspension of a methacrylic acid copolymer,
an aqueous suspension of ethyl cellulose, and an aqueous suspension of polyvinyl
acetate.
The amount of the binder in the matrix may be controlled adequately
depending on the dose of the drug and/or the final size of the microparticle. It may
be present in the matrix in an amount of more than 0 but below 30 wt%, specifically
more than 0 but below 10 wt%, based on solid content.
In an embodiment, the controlled-release microparticle may have an average
particle diameter of, for example, 300 µm or smaller, 250 µm or smaller, or 200 µm or
smaller. Furthermore, the controlled-release microparticle may have an average
particle diameter of, for example, 300-100 µm, 300-150 µm, 250-100 µm, 250-150 µm,
or 200-100 µm. In general, a large amount of coating substance and a long coating
time are required to enable controlled release of a microparticle which is 300 µm or

smaller. However, the controlled-release microparticle of the present disclosure,
which comprises the matrix comprising the pharmacologically active component and
the controlled-release layer comprising the substance which forms a
controlled-release stratum on the matrix, allows effective control of release even
when the particle size is 300 µm or smaller and exhibits comparable or better
dissolution characteristics even when a smaller amount of coating substance is used.
As occasion demands, the controlled-release microparticle may be prepared
into a tablet such as a quickly disintegrating tablet, a suspension tablet or a chewable
tablet or into a capsule by a common tablet making method or by humidifying/drying
or heating as required. For this purpose, a pharmaceutically acceptable additive
may be further included, common examples of which include a plasticizer, a lubricant,
and other supplementary aids.
The present disclosure also provides a method for preparing a
controlled-release microparticle, comprising: preparing a matrix comprising a
pharmacologically active component; and forming a controlled-release layer
comprising a substance which forms a controlled-release stratum on the matrix.
In an embodiment, in the step of preparing the matrix comprising a
pharmacologically active component, a drug, an excipient and a binder may be mixed
until the mixture becomes homogeneous to prepare the matrix. The excipient and
the binder are the same as those described above.
An apparatus used to prepare the matrix is not particularly restricted. For
example, such apparatus as a flow type grahulator or a high shear mixer may be used.
The diameter of the matrix may be controlled adequately such that the final diameter
of the controlled-release microparticle may be 300 µm or smaller.
Through this, the drug may be uniformly distributed in the matrix, and the drug

and the excipient may be bound together by the binder. As a result, the matrix can
release the drug as desired through diffusion and erosion.
Next, the controlled-release layer comprising the substance which forms a
controlled-release stratum is formed on the matrix. The substance which forms a
controlled-release stratum may be different polymer layers depending on purposes.
For example, the polymer layer may be formed by spraying a solution in which the
polymer component is dissolved to the matrix to a thickness required to attain the
desired drug release rate. The polymer that may be used for the polymer layer is the
same as described above.
The examples and experiments will now be described. The following
examples and experiments are for illustrative purposes only and not intended to limit
the scope of the present disclosure.
Preparation of matrix >
Example 1
Tamsulosin hydrochloride (3.33 g) was adequately triturated and mixed with
microcrystalline cellulose powder (Vivapur PH101, 496.67 g). Then, a spherical
matrix comprising tamsulosin hydrochloride was prepared while spraying water (500
g) using a rotary-type fluidized bed apparatus (GPCG-1, Glatt, Germany).
Among the prepared particles, only those having a particle diameter of
150-250 µm (60-100 mesh) were selected.
Example 2
A spherical matrix was prepared in the same manner as in Example 1, except
for spraying a dispersion comprising Eudragit L30D-55 (88.90 g; solid 26.67 g (solid
content = 30%), water 62.23 g) and water (437.77 g). Only the particles having a

particle diameter of 150-250 µm (60-100 mesh) were selected.
Example 3
Tamsulosin hydrochloride (3.33 g) was adequately triturated and mixed with
microcrystalline cellulose (346.67 g), calcium hydrogen phosphate (100 g) and
lactose (50 g). Then, a spherical matrix was prepared while spraying a dispersion
comprising Eudragit L30D-55 (88.90 g; solid 26.67 g (solid content = 30%), water
62.23 g) and water (437.77 g).
Among the prepared particles, only those having a particle diameter of
150-250 µm (60-100 mesh) were selected.
preparation of controlled-release microparticles>
Example,4
To the tamsulosin hydrochloride-containing matrix (800 g) prepared in
Example 1, a 30% aqueous dispersion of ethyl cellulose (ECD, 206.3 g; solid 61.89 g)
and a mixed aqueous dispersion (533.33 g, solid content 15%) of Kollicoat IR (3.26 g,
weight ratio = 9.5:0.5) and triethyl citrate (14.85 g) were repeatedly sprayed by
bottom spraying using the same fluidized bed apparatus to coat to a weight ratio of
10%, 20%, 30% and 40% based on the weight of the microparticle. Then, by
hardening at room temperature and 60 °C for 12 hours, respectively,
controlled-release microparticles with an average particle diameter of 250 µm were
prepared.
Example 5
To the tamsulosin hydrochloride-containing matrix (800 g) prepared in
Example 1, an ECD (190.5 g, solid 57.15 g) and a mixed aqueous dispersion (533.33
g, solid content 15%) of Kollicoat IR (6.35 g, weight ratio = 9:1) and triethyl citrate
(13.70 g) were repeatedly sprayed to coat to a weight ratio of 10%, 15%, 20% and

30% based on the weight of the microparticle. Then, by hardening at room
temperature and 60 °C for 12 hours, respectively, controlled-release microparticles
with an average particle diameter of 230 µm were prepared.
Each controlled-release microparticle (800 g) coated with a weight ratio of
15%, 20% and 30%, respectively, was coated by bottom spraying using the same
fluidized bed apparatus with a mixed solution of Eudragit L30D-55 (381.3 g, solid
114.3 g), talc (34.2 g), triethyl citrate (11.4 g) and purified water (373 g) to a weight
ratio of 20% based on the weight of the controlled-release microparticles. Thus,
enteric-soluble controlled-release microparticles with an average particle diameter of
about 250 µm, coated with a weight ratio of 35%, 40% and 50% were prepared.
Example 6
Controlled-release microparticles with an average particle diameter of 230 µm
were prepared in the same manner as in Example 4, except for spraying an ECD (680
g, solid 204g) and a mixed aqueous dispersion (1984 g, solid content = 15.0%) of
Kollicoat IR (36 g, weight ratio = 8.5:1.5) and triethyl citrate (57.6 g).
Example 7
To the tamsulosin hydrochloride-containing matrix (800 g) prepared in
Example 2, an ECD (680 g, solid 204 g) and a mixed aqueous dispersion (1984 g,
solid content 15.0%) of Kollicoat IR (36 g, weight ratio = 8.5 : 1.5) and triethyl citrate
(57.6 g) were repeatedly sprayed to coat to a weight ratio of 37.2% based on the
weight of the microparticle. Then, by hardening at 60 °C for 12 hours, a
controlled-release microparticle with an average particle diameter of 250 µm was
prepared.
Comparative Example 1
Tamsulosin hydrochloride (20 g) and hydroxypropyl methylcellulose (20 g)

were dissolved in a mixed solution of purified water (76 g) and methanol (684 g).
After putting an inert core (spherical microcrystalline cellulose particle, 1000 g) having
a particle diameter of approximately 50-150 µm in a rotary-type fluidized bed
apparatus (GPCG-1, Glatt, Germany), the core was coated with the mixed solution to
prepare a tamsulosin hydrochloride microparticle.
Separately from this, ethyl cellulose (133.25 g) and hydroxypropyl
methylcellulose (46.75 g) were dissolved in a mixed solution of purified water (174.5
g) and methanol (5645.5 g) to prepare a coating solution.
The tamsulosin hydrochloride microparticle (1000 g) was put in the same
fluidized bed apparatus and coated with the separately prepared coating solution to a
weight ratio of 18% based on the microparticle to prepare a controlled-release
microparticle.
The prepared controlled-release microparticle (1000 g) was put in the same
fluidized bed apparatus and coated with a mixed solution of an ECD (500 g), Eudragit
L30D-55 (1000 g), Eudragit NE30D (166.75 g) and purified water (1666.75 g) to a
weight ratio of 50% based on the microparticle to prepare an enteric-soluble
controlled-release microparticle with an average diameter of about 250 µm.

Each of the tamsulosin hydrochloride 0.2 mg microparticles prepared in
Examples and Comparative Example 1 was filled in a capsule and dissolution rate
was compared according to the Korean Pharmacopeia Dissolution Test No. 2. The
test was performed at 75 rpm, using a disintegration test solution no. 2 (pH 6.8, 500
mL). Samples (10 mL) were taken at 30 minutes, 1 hour and 4 hours after initiation
of the dissolution test. After addition of 0.5 N HCI (1.0 mL) followed by filtration, the
filtrate was quantitated by high-performance liquid chromatography (HPLC) under the

following conditions. 6 samples were tested for each microparticle.
Column: LUNA C18 (4.6 x 150 mm, 5 urn)
Detector: UV 225 nm
Flow rate: to maintain tamsulosin residence time at about 6 minutes
Sample injection volume: 100 µL
Column temperature: 40 °C
Mobile phase: Perchloric acid (8.7 mL) and sodium hydroxide (3.0 g)
dissolved in water (1900 mL) to prepare a sodium hydroxide test solution. After
adjusting to pH 2.0, water was added to make final volume 2000 mL. Acetonitrile
(600 mL) was added to the resultant solution (1400 mL) for use as the mobile phase.
The result is shown in Figure 1. It can be seen that the controlled-release
microparticle of Example 5 (coated to a weight ratio of 35%) exhibits a similar
dissolution profile as that of Comparative Example 1 (coated to a weight ratio of 58%).
Consequently, it can be confirmed that the controlled-release microparticle according
to the present disclosure exhibits comparable dissolution characteristics as
Comparative Example 1 even with a smaller amount of coating substance and less
coating time.
Those skilled in the art will appreciate that the conceptions and specific
embodiments disclosed in the foregoing description may be readily utilized as a
basis for modifying or designing other embodiments for carrying out the same
purposes of the present disclosure. Those skilled in the art will also appreciate
that such equivalent embodiments do not depart from the spirit and scope of the
disclosure as set forth in the appended claims.

[CLAIMS]
[Claim 1]
A controlled-release microparticle comprising:
a matrix comprising a pharmacologically active component; and
a controlled-release layer comprising a substance which forms a
controlled-release stratum on the matrix.
[Claim 2]
The controlled-release microparticle according to claim 1, wherein the
substance which forms a controlled-release stratum is a polymer selected from a
group consisting of a water-insoluble polymer, a gastric-soluble polymer, an
enteric-soluble polymer, a water-soluble polymer, and a mixture thereof.
[Claim 3]
The controlled-release microparticle according to claim 2, wherein the
water-insoluble polymer is one or more selected from a group consisting of ethyl
cellulose, cellulose ether, an ethyl acrylate-methyl
methacrylate-chlorotrimethylammoniumethyl methacrylate copolymer, polyvinyl
acetate, an ethyl acrylate-methyl methacrylate copolymer, and a dispersion thereof.
[Claim 4]
The controlled-release microparticle according to claim 2, wherein the

gastric-soluble polymer is one or more selected from a group consisting of polyvinyl
acetal diethylamino acetate, and a methyl methacrylate-butyl
methacrylate-dimethylaminoethyl methacrylate copolymer.
[Claim 5]
The controlled-release microparticle according to claim 2, wherein the
enteric-soluble polymer is one or more selected from a group consisting of
hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose
phthalate, hydroxymethylethyl cellulose phthalate, carboxymethylethyl cellulose, a
methacrylic acid-methyl methacrylate copolymer, and a methacrylic acid-ethyl
acrylate copolymer.
[Claim 6]
The controlled-release microparticle according to claim 2, wherein the
water-soluble polymer is one or more selected from a group consisting of
hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and
polyvinyl alcohol.
[Claim 7]
The controlled-release microparticle according to claim 1, wherein the
controlled-release layer accounts for 15-60 wt% based on the total weight of the
controlled-release microparticle.

[Claim 8]
The controlled-release microparticle according to claim 1, wherein the active
component is selected from a group consisting of: an antidiabetic selected from a
group consisting of acetohexamide, insulin, tolbutamide, desmopressin, and glipizide;
a diuretic selected from a group consisting of hydrochlorothiazide, polythiazide, and
triamterene; a bronchodilator selected from a group consisting of aminopyrine,
formoterol maleate, and theophylline; an antitussive selected from a group consisting
of codeine phosphate, noscapine, dimemorfan phosphate, and dextromethorphan; an
antiarrhythmic agent selected from a group consisting of quinidine nitrate, digitoxin,
propafenone hydrochloride, and procainamide; a topical anesthetic selected from a
group consisting of ethyl aminobenzoate, lidocaine, and dibucaine hydrochloride; an
antiepileptic selected from a group consisting of phenytoin, ethosuximide, and
primidone; a synthetic adrenocortical steroid selected from a group consisting of
hydrocortisone, prednisolone, triamcinolone, and betamethasone; a peptic ulcer drug
selected from a group consisting of famotidine, ranitidine hydrochloride, cimetidine,
sucralfate, sulpiride, teprenone, plaunotol, 5-aminosalicylic acid, sulfasalazine,
omeprazole, pantoprazole, and lansoprazole; a central nervous system drug selected
from a group consisting of indeloxazine, idebenone, tiapride hydrochloride,
bifemelane hydrochloride, and calcium homopantothenate; an antihyperlipidemic
agent selected from a group consisting of pravastatin sodium, simvastatin, lovastatin,
fluvastatin, and atorvastatin; an antibiotic selected from a group consisting of phthalyl
ampicillin hydrochloride, cefotetan, and josamycin; a benign prostatic hypertrophy
therapeutic agent selected from a group consisting of tamsulosin hydrochloride,
doxazosin mesylate, and terazosin hydrochloride; an antiasthmatic agent selected

from a group consisting of pranlukast, the philcast, albuterol, ambroxol, budesonide,
and levalbuterol; a gastroprokinetic agent selected from a group consisting of
mosapride, mosapride citrate, itopride, itopride hydrochloride, cisapride, cisapride
monohydrate, cisapride tartrate, domperidone, domperidone maleate,
metoclopramide, metoclopramide hydrochloride, trimebutine, trimebutine maleate,
clebopride, clebopride maleate, bromopride, and levosulpiride; an anti-depressant; a
peripheral circulation improving agent; an antithrombotic agent; an antihypertensive;
a heart failure drug; a diabetic complication drug; a skin ulcer drug; and a combination
thereof.
[Claim 9]
The controlled-release microparticle according to claim 1, wherein the matrix
further comprises an excipient and a binder.
[Claim 10]
The controlled-release microparticle according to claim 9, wherein the
excipient is selected from a cellulose derivative, a saccharide, calcium phosphate,
and a mixture thereof.
[Claim 11]
The controlled-release microparticle according to claim 10, wherein the
cellulose derivative is selected from a group consisting of microcrystalline cellulose
and low-substituted hydroxypropyl cellulose, the saccharide is selected from a group

consisting of lactose, starch and pregelatinized starch, and the calcium phosphate is
selected from a group consisting of anhydrous calcium hydrogen phosphate, calcium
hydrogen phosphate dihydrate, and tricalcium phosphate.
[Claim 12]
The controlled-release microparticle according to claim 9, wherein the binder
is one or more selected from water, an aqueous suspension of a methacrylic acid
copolymer, an aqueous suspension of ethyl cellulose, and an aqueous suspension of
polyvinyl acetate.
[Claim 13]
The controlled-release microparticle according to claim 1, wherein the
controlled-release microparticle has an average particle diameter of 300 µm or
smaller.
[Claim 14]
The controlled-release microparticle according to claim 1, wherein the
controlled-release microparticles is prepared into a tablet or a capsule.
[Claim 15]
A method for preparing the controlled-release microparticle according to any
one of claims 1 to 14, comprising:

preparing a matrix comprising a pharmacologically active component; and
forming a controlled-release layer comprising a substance which forms a
controlled-release stratum on the matrix.

Disclosed is a controlled-release microparticle: including a matrix
comprising a pharmacologically active component; and a controlled-release layer
comprising a substance which forms a controlled-release stratum on the matrix.
The disclosed controlled-release microparticie not only allows effective dual
release control of a drug but can also exhibit outstanding dissolution
characteristics even when a small amount of coating substance is used.