KR102090135B1 - Orally disintegrating tablet comprising solifenacin or its pharmaceutically acceptable salts, and preparing method thereof - Google Patents

Abstract

The present invention 1) a core layer; 2) a drug layer comprising solifenacin or a pharmaceutically acceptable salt thereof, and a binder as an active ingredient; And 3) a coating layer coated with a coating base on the drug layer. In addition, the pharmaceutical formulation of the present invention does not contain a plasticizer. The present invention relates to an oral disintegrating tablet prepared by the pharmaceutical preparation.

Description

Orally disintegrating tablet comprising solifenacin or its pharmaceutically acceptable salts, and preparing method thereof

The present invention relates to a pharmaceutical preparation comprising solifenacin or a pharmaceutically acceptable salt thereof having a blocked bitter taste, and an oral disintegrating tablet prepared using the same.

Tablets that require daily medication for a long period of time have low medication compliance, so tablets that can disintegrate quickly in the oral cavity (e.g., oral disintegrating tablets) are preferred in terms of convenience and compliance when taken. Do. In particular, oral disintegrating tablets are one of the preferred formulations because they can be easily taken by elderly people with weak swallowing power.

Solifenacin is represented by the following formula (I), and its chemical name is (1R, 3'R) -3'-quinuclidinyl-1-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate to be.

[Formula I]

In European Patent No. 801068, the series of quinoclidine derivatives containing solifenacin or a salt thereof has excellent selective antagonistic action against muscarinic M3 receptors, neurogenic anuria, neurogenic bladder, enuresis, unstable bladder, bladder It has been reported to be useful as a preventive treatment for urinary diseases such as spasticity and chronic cystitis, chronic obstructive pulmonary disease, chronic bronchitis, and respiratory diseases such as asthma and rhinitis.

On the other hand, solifenacin and its pharmaceutically acceptable salts are known to have high solubility and very strong bitterness for various solvents. Therefore, in order to develop an oral disintegrating tablet of solifenacin or a pharmaceutically acceptable salt thereof, it is necessary to block the bitter taste.

In general, oral disintegrating tablets containing an active ingredient with a strong bitter taste can mask the bitter taste by adding a sweetener. In addition, since even if a small amount of the pellets containing the active ingredient remains in the mouth and breaks, bitter taste may occur, so the pellets contain sweetener components and the like. However, when the sweetener is mixed with the active ingredient and coated with the same layer, the generation of a related substance is promoted, and thus there is a fear that stability is reduced.

In addition, Korean Registered Patent No.1342786 for a stable particulate pharmaceutical composition of solifenacin or a salt thereof contains a drug using a binder (polyvinylpyridone, PVP) or hydroxypropylmethylcellulose (HPMC) commonly used by those skilled in the art ( As a formulation obtained by coating solifenacin succinate, the stability was confirmed under accelerated test conditions (40 ° C, 75% RH, bottle sealing condition). As a result, the residual rate of solifenacin succinate decreased and after 2 months, solifenacin It is described that the amount of oxidized product of succinate is not more than 0.4% and does not have sufficient stability.

In addition, in Korean Patent No. 13,428, when preparing a fine particle by spraying a drug solution onto core particles to obtain a granular substance with a bitter taste blocked, it is necessary to dissolve solifenacin or its salt in a solution and spray it. It is described that solifenacin cannot be secured in the case of obtaining granular material by dissolving solifenacin in a solvent because solipenacin is easily changed to a crystalline form and decomposition products are formed when it is changed from an amorphous form to a crystalline form.

Crystalline forms of solifenacin exist in various forms, and compounds of different crystalline forms have different physical properties such as melting point, solubility and density, and particularly show differences in stability.

The present invention is to provide an oral disintegrating tablet using a pharmaceutical preparation, which is blocked and stable in bitter taste including solifenacin or a pharmaceutically acceptable salt thereof. In pharmaceutical preparations using solifenacin or a pharmaceutically acceptable salt thereof as an active ingredient, solifenacin is easy to change into a crystalline form and a degradation product is generated when it is changed from an amorphous form to a crystalline form. The present inventors have surprisingly found that the pharmaceutical preparations present in a high content amorphous form are stable for a long time and completed the present invention.

The present inventors have developed a formulation that maintains stability while masking bitter taste using hydroxypropyl methylcellulose (HPMC) as a binder to obtain a granular substance of solifenacin or a pharmaceutically acceptable salt thereof.

In addition, a plasticizer is generally used to coat the granular material, but the present invention provides a pharmaceutical formulation that does not use a plasticizer. The plasticizer is added to the coating base to increase flexibility and strength, but when using a plasticizer, it is difficult to meet the best process conditions.

In the formulation of the present invention, there is no problem in coating the granular material even without the use of a plasticizer, so that the manufacturing cost is reduced and the preparation of the preparation is easy. In particular, in order to minimize the discomfort of the oral disintegrating tablet, the size of the granules can be adjusted to a small size, and side effects to the human body can be reduced.

In particular, since solifenacin is prescribed to elderly patients over the age of 60, it is possible to increase the patient's medication compliance by controlling the size of the particles small.

When preparing fine particles by spraying solifenacin or a salt thereof to the core particles in order to obtain a granular substance blocking the bitter taste, solifenacin is likely to change into a crystalline form and decomposition products are formed when changed from an amorphous form to a crystalline form. The stability of phenacin cannot be ensured. Accordingly, the present inventor has prepared a pharmaceutical formulation containing stabilized solifenacin, which effectively shields the bitter taste and has no foreign body sensation in the mouth after taking it, and has a small particle size because it does not contain a plasticizer, and at the same time maintains an amorphous form without changing for a long time. .

Specifically, the present invention

1) a drug layer comprising solifenacin or a pharmaceutically acceptable salt thereof, and a binder as an active ingredient; And

2) It provides a pharmaceutical formulation having a bitter taste, including a coating layer coated with a coating base on the drug layer.

In addition, the present invention

1) core layer;

2) a drug layer coated on the core layer and comprising solifenacin or a pharmaceutically acceptable salt thereof, and a binder as an active ingredient; And

3) It provides a pharmaceutical formulation having a bitter taste, including a coating layer coated with a coating base on the drug layer.

That is, the present invention provides a pharmaceutical formulation consisting of two or more layers comprising no core layer or three or more layers comprising the core layer.

(a) core layer

In the present invention, the core layer may be selected from the group consisting of white sugar, mannitol, sorbitol, lactose, potato starch, corn starch, hydroxyethyl cellulose, microcrystalline cellulose, platinum, carnauba wax, microcrystalline wax, and mixtures thereof.

(b) drug layer

In the present invention, the drug layer may include solifenacin or a pharmaceutically acceptable salt thereof as an active ingredient. In addition, the present invention provides a pharmaceutical preparation in which solifenacin or a pharmaceutically acceptable salt thereof as the active ingredient is mainly present in an amorphous form. Preferably at least 80%, more preferably at least 90%, most preferably at least 95% amorphous solifenacin or a pharmaceutically acceptable salt thereof. This is based on the inventors' discovery that the pharmaceutical preparations can keep solifenacin stable by containing a high content of amorphous.

 In the present invention, polyvinylpyrrolidone (PVP), methyl cellulose or hydroxypropylmethylcellulose (HPMC) may be used as the binder, and it is preferable to use hydroxypropylmethylcellulose.

In addition, the drug layer in the present invention, sodium citrate (Sodium citrate), citric acid (Citric acid), butylated hydroxyanisole (Butyl hydroxy anisole), butylated hydroxy toluene (Butylated hydroxy toluene) and propyl gallate ( Propyl gallate) may include one or more antioxidants selected from the group consisting of, but is not limited to.

(c) coating layer

In the present invention, a methacrylic acid copolymer, preferably Eudragit, may be used as a coating base. Specifically, butyl methacrylate- (2-dimethylaminoethyl) methacrylic acid-methyl methacrylate 1: 2: 1 copolymer (Eudragit E), methacrylic acid-methyl methacrylate 1: 1 copolymer (Eudragit L), ethyl acrylate- Methyl methacrylate-trimethylammonioethyl methacrylate chloride 1: 2: 0.2 copolymer (Eudragit RL), ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate chloride 1: 2: 0.1 copolymer (Eudragit RS), acrylic acid Ethyl-methyl acrylate 2: 1 copolymer (Eudragit NE or Eudragit NM), and mixtures thereof can be used, preferably ethyl acrylate-methyl acrylate 2: 1 copolymer (Eudragit NE30D, Eudragit NE40D or Eudragit NM30D) ), Methacrylic acid-ethyl acrylate 1: 1 copolymer (Eudragit L30-D55 or Eudragit L100-55), and mixtures thereof may be used, but is not limited thereto. At this time, the mixing ratio of ethyl acrylate-methyl acrylate 2: 1 copolymer and methacrylic acid-ethyl acrylate 1: 1 copolymer may be 0.1: 1 to 3: 1, preferably 0.5 to 2: 1, It can reduce agglomeration and twinning and improve bitterness and foreign body sensation.

The present invention provides pharmaceutical formulations having a particle size of 50 to 200 μm, preferably 80 to 170 μm. When the particle size of the pharmaceutical preparation is in the above range, there is little foreign body feeling when taking.

The pharmaceutical preparation of the present invention may be formulated into various forms of oral preparations such as pellets, capsules, tablets, powders, granules, oral disintegrating tablets or suspensions, and oral disintegrating tablets are preferred.

Orally disintegrating tablet means a pharmaceutical preparation that disintegrates in less than 1 minute (preferably within 40 seconds) by saliva substantially without taking water when taking the preparation. According to one embodiment of the present invention, the pharmaceutical preparation prepared above may be formulated in the form of an oral disintegrating tablet by mixing with a pharmaceutically acceptable additive (for example, a diluent) and then tableting.

In the present invention, the oral disintegrating tablet has a hardness of 1-5 kp, preferably 2-4 kp, and more preferably 3 kp. At this time, the wear resistance is low and the disintegration time can be adjusted within 60 seconds.

The diluent may be selected from the group consisting of xylitol, trehalose, sorbitol, maltose, sorbitol, erythritol, glucose, maltitol, mannitol, white sugar, lactose and hydrates thereof.

The oral disintegrating tablet of the present invention may include, in addition to the above components, a disintegrating agent, acidifying agent, flavoring agent, lubricant, and combinations thereof, which are commonly used as pharmaceutically acceptable additives, and may further include a sweetening agent. .

The disintegrant may be selected from the group consisting of crospovidone, sodium starch glycolate, croscarmellose sodium, low-substituted hydroxypropylcellulose, starch, alginic acid or its sodium salt, and mixtures thereof.

The acidulant may be citric acid anhydride, tartaric acid, malic acid, and the like, and as the fragrance, peppermint flavor, strawberry flavor, peppermint flavor powder, menthol, lemon flavor powder, orange flavor powder, etc. may be used.

The lubricant is sodium stearyl fumarate, magnesium stearate, calcium stearate, white sugar, fatty acid stearate, sucrose fatty acid ester, talc, hydrogenated vegetable oil, high melting point wax, glyceryl fatty acid esters, glyceryl behenate And mixtures thereof.

The pharmaceutical formulation according to the present invention

(a) dissolving solifenacin or a pharmaceutically acceptable salt thereof, and a binder in a solvent to prepare a drug solution to form a drug layer; And

(b) dissolving the coating base in a solvent to prepare a coating solution to form a coating layer.

In the present invention, ethanol, acetone, a mixture of ethanol and acetone, or water may be used as the solvent, and water is preferably used. When water is used as a solvent in the present invention, it can be confirmed that the particle size of the pharmaceutical formulation can be controlled to be small, the effect of blocking bitterness is excellent, and the electrostatic phenomenon is improved during the twinning and coating process.

At this time, the temperature may be in the range of 20 to 35 ° C, preferably 25 to 30 ° C.

In addition, in order to prepare the pharmaceutical preparation, an oral disintegrating tablet is prepared by mixing with an additional process, for example, a pharmaceutically acceptable additive, followed by tableting, or by mixing with an excipient for a pharmaceutically acceptable suspension. The pharmaceutical formulation may be formulated by further comprising a step of preparing.

Coating in the manufacturing method of the present invention can be made by using a conventional method used for the coating of the formulation in the art, for example, a fan coating method, a fluidized bed coating method or a compression coating method without limitation, but coated on a fluidized bed coating device A fluidized bed coating method in which a preparation to be added is flowed with air blown downward and sprayed to coat the coating solution is preferred.

The pharmaceutical formulation of the present invention provides an oral disintegrating tablet that effectively shields the bitter taste of solifenacin and has no foreign body sensation in the mouth after taking, and is capable of rapid disintegration in the oral cavity without water. In addition, since no plasticizer is used, it is inexpensive, easy to formulate, and can be prepared as a formulation having a small particle size. In particular, solifenacin can be stabilized so that the amorphous form is maintained without changing to a crystalline form even under accelerated conditions.

1 shows DSC measurement results of solifenacin succinate.
2 shows the DSC measurement results of F-melt.
Figure 3 shows the results of DSC measurement of granular sugar (Sugar sphere).
4 shows the results of DSC measurement of solifenacin oral disintegrating tablet (Example 1).

Hereinafter, the present invention will be described in more detail through examples. These examples are intended to illustrate the present invention in more detail, and the scope of the present invention is not limited by these examples.

[Example 1]

Step 1. Preparation of the solifenacin drug layer

A drug layer solution was prepared by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of hydroxypropyl methylcellulose (HPMC), 1.0 mg of sodium citrate, and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. Thereafter, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was placed in a fluidized bed coater, and the drug layer solution was sprayed under conditions of an air supply temperature of 70 ° C., an air flow rate of 40 m ³ / min, and an injection pressure of 2.0 bar. It was prepared.

Step 2. Preparation of coating layer

The pellet formed with the drug layer obtained in step 1 was coated with a coating solution prepared by dispersing 10.0 mg of Eudragit NE 30D, 5.0 mg of Eudragit L30-D55 and 10.0 mg of talc in 150.0 mg of purified water in a fluid bed coater to prepare a coating layer.

The coating conditions were performed under a supply temperature of 60 ° C, an air volume of 50 m ³ / min, and an injection pressure of 2.0 bar.

Step 3. Preparation of oral disintegrating tablet

Efmelt (spray dried mannitol), crospovidone, aspartame, and sodium stearyl fumarate were mixed in a mixer so that the weight of the coated pellet obtained in step 2 was 200 mg, and tableted to a hardness of 2-5 kp, solifenacin succinic acid per tablet. Tablets containing 10.0 mg of salt were prepared.

[Example 2]

A drug layer solution was prepared by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of polyvinylpyrrolidone (PVP), 1.0 mg of sodium citrate and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. Thereafter, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was placed in a fluidized bed coater, and the drug layer solution was sprayed under conditions of an air supply temperature of 70 ° C., an air flow rate of 40 m ³ / min, and an injection pressure of 2.0 bar. It was prepared. Steps 2 and 3 were performed in the same manner as in Example 1.

[Example 3]

A drug layer solution was prepared by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of methylcellulose (MC), 1.0 mg of sodium citrate and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. Thereafter, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was placed in a fluidized bed coater, and the drug layer solution was sprayed under conditions of an air supply temperature of 70 ° C., an air flow rate of 40 m ³ / min, and an injection pressure of 2.0 bar. It was prepared. Steps 2 and 3 were performed in the same manner as in Example 1.

[Example 4]

A drug layer solution was prepared by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of hydroxypropyl methylcellulose (HPMC), 1.0 mg of citric acid and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. Thereafter, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was placed in a fluidized bed coater, and the drug layer solution was sprayed under conditions of an air supply temperature of 70 ° C., an air flow rate of 40 m ³ / min, and an injection pressure of 2.0 bar. It was prepared.

[Example 5]

Prepare a drug layer solution by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of hydroxypropyl methylcellulose (HPMC), 1.0 mg of butylated hydroxy anisole and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. Did. Subsequently, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was put in a fluid bed coater, and the drug layer solution was sprayed under coating conditions under a supply temperature of 70 ° C., an air flow rate of 40 m ³ / min, and a spray pressure of 2.0 bar. Was prepared.

[Example 6]

A drug layer solution was prepared by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of hydroxypropyl methylcellulose (HPMC), 1.0 mg of butylated hydroxy toluene and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. . Thereafter, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was placed in a fluidized bed coater, and the drug layer solution was sprayed under conditions of an air supply temperature of 70 ° C., an air flow rate of 40 m ³ / min, and an injection pressure of 2.0 bar. It was prepared.

[Example 7]

A drug layer solution was prepared by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of hydroxypropyl methylcellulose (HPMC), 1.0 mg of propyl gallate and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. Subsequently, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was placed in a fluid bed coater, and the drug layer was sprayed under conditions of an air supply temperature of 70 ° C., an air volume of 40 m ³ / min, and a spray pressure of 2.0 bar. It was prepared.

[Comparative Example 1]

Comparative Example without Antioxidants

A drug layer solution was prepared by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of hydroxypropyl methylcellulose (HPMC) and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. Thereafter, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was placed in a fluidized bed coater, and the drug layer solution was sprayed under conditions of an air supply temperature of 70 ° C., an air flow rate of 40 m ³ / min, and an injection pressure of 2.0 bar. It was prepared. Steps 2 and 3 were performed in the same manner as in Example 1.

[Comparative Example 2]

If the drug layer contains a plasticizer

Prepare a drug layer solution by dissolving 10.0 mg of solifenacin succinate, 4.5 mg of hydroxypropyl methylcellulose (HPMC), 1.0 mg of sodium citrate, 1.0 mg of TEC and 3.5 mg of talc in 100.0 mg of purified water with stirring and dissolution. Did. Subsequently, 30 mg of granular white sugar (Sugar sphere) having a size of 100 to 130 μm was put in a fluid bed coater, and the drug layer solution was sprayed under coating conditions under a supply temperature of 70 ° C., an air flow rate of 40 m ³ / min, and a spray pressure of 2.0 bar. Was prepared. Steps 2 and 3 were performed in the same manner as in Example 1.

[Comparative Example 3]

When the coating layer contains a plasticizer

The coating layer obtained by dispersing the pellets formed with the drug layer obtained in Step 1 of Example 1 in a fluid bed coater by dispersing TEC 1.0, Eudragit NE 30D 10.0 mg, Eudragit L30-D55 5.0 mg, talc 10.0 mg in purified water 150.0 mg and coating layer Was prepared. The coating conditions were performed under a supply temperature of 60 ° C, an air volume of 50 m ³ / min, and an injection pressure of 2.0 bar. Step 3 proceeded in the same manner as in Example 1.

[Comparative Example 4]

When both the drug layer and the coating layer contain a plasticizer

The drug layer pellet obtained in Comparative Example 2 was coated with a coating solution prepared by dispersing TEC 1.0, Eudragit NE 30D 10.0 mg, Eudragit L30-D55 5.0 mg, and talc 10.0 mg in purified water 150.0 mg in a fluid bed coater to prepare a coating layer. Step 3 proceeded in the same manner as in Example 1.

[Experimental Example 1]

Amorphous confirmation test results

Differential scanning calorimetry (DSC) can be used as a technique for determining crystalline compounds. DSC is a measure of the heat transfer temperature at which crystals absorb or release heat when the crystal structure of a compound changes or melts, and their transition temperature profiles may be different when the crystal form is different.

As shown in the test results of FIGS. 1 to 4, FIG. 1 shows DSC measurement results of crystalline solifenacin succinate, and FIG. 4 shows solifenacin orally disintegrating tablets stored for up to 6 months of acceleration (Example 1). DSC shows the measurement results. That is, it was confirmed that FIG. 4 does not show the peak of crystalline solifenacin (FIG. 1), but only the peaks of the excipients, efmelt (FIG. 2) and granular white sugar (FIG. 3). Therefore, it can be seen that the oral disintegrating tablet of solifenacin according to the present invention maintains the amorphous form for a long time.

[Experimental Example 2]

Stability test by hydrophilic polymer type

As a result of the severe test, as a result of confirming the commercial products Betsy Care tablets and the related substances of Examples 1 to 3, as shown in [Table 4], it was confirmed that the related substances were kept low in Examples 1 to 3 compared to the Betsy Care tablets. .

Storage condition: 60 ℃, 25% RH

Packaging type: sealed glass vials

Test items: Related substances

* N.D: Non Detectable

[Experimental Example 3]

Stability test according to antioxidant type

The severe test results according to the types of antioxidants are shown in [Table 5], and it was confirmed that the preparations containing antioxidants were stable because the related substances were kept low in Examples 1 and 4 to 7 compared to Comparative Example 1 Did.

Storage condition: 60 ℃, 25% RH

Packaging type: sealed glass vials

Test items: Related substances

[Experimental Example 4]

Dissolution rate according to plasticizer content

The dissolution test results are shown in [Table 6], and it was confirmed that no significant change in dissolution rate of the pellet mixture and the tablet was observed regardless of the presence or absence of a plasticizer.

Test item: Dissolution test

Test condition: Paddle 50rpm, pH 1.2

[Experimental Example 5]

Bitter taste masking and formulation test

In the same manner as in Example 1, Examples 8 and 9, Comparative Examples 5 and 6 tablets were prepared with the components and contents shown in Table 7, and bitter taste masking was confirmed.

As a result of confirming the bitterness masking, it was confirmed that the tablet of Comparative Example 5 did not have a bitterness masking mask. In addition, in Comparative Example 6, a twinning phenomenon in which pellets stick to each other and a caking phenomenon in which pellets agglomerate occurred during the preparation of the formulation. On the other hand, Examples 1, 8 and 9 masked the bitter taste, and did not exhibit twinning and caking phenomena in the manufacturing process.

After all, when the ethyl acrylate-methyl acrylate 2: 1 copolymer (Eudragit NE 30D) and the methacrylic acid-ethyl acrylate 1: 1 copolymer (Eudragit L30-D55) are used together, the bitter taste masking and preparation of the preparation It turns out that it shows an excellent effect in a process.

Claims (16)

1) a drug layer comprising solifenacin or a pharmaceutically acceptable salt thereof, and a binder as an active ingredient; And
2) a coating layer coated with a coating base on the drug layer,
The coating base is a pharmaceutical preparation, characterized in that a mixture of ethyl acrylate-methyl acrylate 2: 1 copolymer and methacrylic acid-ethyl acrylate 1: 1 copolymer. 1) core layer;
2) a drug layer comprising solifenacin or a pharmaceutically acceptable salt thereof, and a binder as an active ingredient; And
3) a coating layer coated with a coating base on the drug layer,
The coating base is a pharmaceutical preparation, characterized in that a mixture of ethyl acrylate-methyl acrylate 2: 1 copolymer and methacrylic acid-ethyl acrylate 1: 1 copolymer. The pharmaceutical preparation according to claim 1 or 2, wherein solifenacin or a pharmaceutically acceptable salt thereof is present in an amorphous form. The pharmaceutical preparation according to claim 1 or 2, wherein the active ingredient is solifenacin succinate. The pharmaceutical preparation according to claim 1 or 2, wherein the binder is selected from one or more of the group consisting of hydroxypropyl methylcellulose, polyvinylpyrrolidone and methylcellulose. The pharmaceutical preparation according to claim 1 or 2, which does not contain a plasticizer. The method according to claim 1 or 2, wherein the drug layer comprises one or more antioxidants selected from the group consisting of sodium citrate, citric acid, butylated hydroxyanisole, butylated hydroxytoluene and propyl gallate. Pharmaceutical formulation characterized by. delete delete delete The pharmaceutical according to claim 1 or 2, wherein the ethyl acrylate-methyl acrylate 2: 1 copolymer and the methacrylic acid-ethyl acrylate 1: 1 copolymer are included in a weight ratio of 0.1: 1 to 3: 1. Formulation. The pharmaceutical preparation according to claim 11, wherein the ethyl acrylate-methyl acrylate 2: 1 copolymer and the methacrylic acid-ethyl acrylate 1: 1 copolymer are included in a weight ratio of 0.5: 1 to 2: 1. The pharmaceutical formulation according to claim 1 or 2, wherein the pharmaceutical formulation has a particle size of 80 to 170 μm. An oral disintegrating tablet prepared with the pharmaceutical preparation of claim 1 or 2. (a) dissolving solifenacin or a pharmaceutically acceptable salt thereof, and a binder in a solvent to prepare a drug solution to form a drug layer; And
(b) dissolving the coating base in a solvent to prepare a coating solution to form a coating layer,
The coating base is a method of manufacturing a pharmaceutical preparation, characterized in that a mixture of ethyl acrylate-methyl acrylate 2: 1 copolymer and methacrylic acid-ethyl acrylate 1: 1 copolymer. 16. The method of claim 15, wherein the solvent is water.

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