JP6805699B2 - Pharmaceutical compositions, methods for producing pharmaceutical compositions, and methods for improving the stability of amorphous materials. - Google Patents

Description

The present invention relates to a pharmaceutical composition, a method for producing a pharmaceutical composition, and a method for improving the stability of an amorphous substance.

The amorphous form of solifenacin is known as an active ingredient of overactive bladder agents, but the stability of the amorphous form is low, and the amorphous form changes over time or decomposes to generate analogs. Therefore, various amorphous pharmaceutical compositions of solifenacin have been developed in order to improve the stability of the amorphous material.

As such an amorphous pharmaceutical composition of soliphenacin, Patent Document 1 describes a pharmaceutical composition containing an amorphous substance of soliphenacin or a salt thereof, citric acid, sodium metabisulfite, and ethylenediaminetetraacetate. The thing is disclosed.

Japanese Patent No. 4816828

However, the pharmaceutical composition of Patent Document 1 is not yet sufficient in terms of the stability of the amorphous form of solifenacin, and there is room for improvement.

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a pharmaceutical composition having high stability of an amorphous form of solifenacin and a method for improving the stability of an amorphous form of solifenacin. And.

By incorporating a copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer in the pharmaceutical composition together with the amorphous body of soriphenacin, the present inventors can improve the stability of the amorphous body of soriphenacin. We have found that it is improved, and have completed the present invention. More specifically, the present invention provides the following.

(1) A pharmaceutical composition containing an amorphous form of solifenacin and / or an amorphous form of a salt thereof, and a copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer.

(2) The pharmaceutical composition according to (1), wherein the amorphous substance of solifenacin and / or the amorphous substance of a salt thereof contains the form of a solid dispersion dispersed in the copolymer.

(3) The amorphous body of soriphenacin and / or the amorphous body of soriphenacin with respect to the total content of the amorphous body of soriphenacin and / or the amorphous body of the salt thereof and the crystalline body of soriphenacin and / or the crystalline body of the salt thereof. The pharmaceutical composition according to (1) or (2), wherein the content of the amorphous substance of the salt thereof is more than 77% by mass.

(4) The mass ratio of the amorphous substance of solifenacin and / or the amorphous substance of the salt thereof to the copolymer is 1: 2 to 1:20, according to (1) to (3). The pharmaceutical composition according to any one.

(5) The pharmaceutical composition according to any one of (1) to (4), wherein the dosage form is a tablet.

(6) The pharmaceutical composition according to any one of (1) to (5), wherein the copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer is polyvinyl alcohol-polyethylene glycol-graft copolymer.

(7) In a pharmaceutical composition containing an amorphous substance of solifenacin and / or an amorphous substance of a salt thereof,
Further, a method for improving the stability of an amorphous form of solifenacin and / or an amorphous form of a salt thereof by containing a copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer.

(8) The method for improving stability according to (7), wherein the copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer is a polyvinyl alcohol-polyethylene glycol-graft copolymer.

According to the present invention, the stability of the amorphous form of solifenacin can be improved.

Hereinafter, embodiments of the present invention will be described, but the present invention is not limited in any way.

<Pharmaceutical composition>
The pharmaceutical composition of the present invention contains an amorphous form of solifenacin and / or an amorphous form of a salt thereof, and a copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer. As described above, by incorporating the above-mentioned copolymer in the pharmaceutical composition, it is possible to obtain high stability of the amorphous form of solifenacin. In the present invention, the stability of the amorphous body of solifenacin means the stability of maintaining the morphology of the amorphous body by suppressing the conversion from the amorphous body to the crystalline body, and solifenacin. Includes both stability to the decomposition of amorphous materials (including the resulting decomposition of solifenacin analogs).

The pharmaceutical composition of the present invention may contain an amorphous form of solifenacin as an active ingredient, or may contain an amorphous form of a salt of solifenacin.

The amorphous salt of soriphenacin is not particularly limited as long as it is a pharmaceutically acceptable salt, and is, for example, an inorganic acid such as hydrochloride, hydroiodide, hydrobromide, nitrate, or sulfate. Salts with, succinates, citrates, oxalates, acetates, malates, tartrates, maleates, fumarates, salts with organic acids such as benzenesulfonates, calcium salts, magnesium Examples thereof include salts with alkaline earth metals such as salts, salts with alkali metals such as lithium salt, potassium salt and sodium salt, salts with organic bases such as ethylenediamine salt, diethanolamine salt and N-methylglucamine salt. .. These may be used alone or in combination of two or more. The pharmaceutically acceptable salt is preferably a salt with an organic acid, and among the salts with an organic acid, it is more preferable to use succinate. Further, the amorphous substance of solifenacin and / or the amorphous substance of a salt thereof may be an anhydride thereof or a solvate such as a hydrate.

In the pharmaceutical composition of the present invention, the content of the amorphous substance of solifenacin and / or the amorphous substance of the salt thereof is not particularly limited, and is, for example, 0.01 to 0.01 to the mass of the entire pharmaceutical composition. It may be appropriately changed within the range of 90.0% by mass, but it is preferably 0.05 to 85% by mass, more preferably 0.05 to 80% by mass, and 0.05 to 50% by mass. %, More preferably 0.05 to 10% by mass, and particularly preferably 1.5 to 3.5% by mass. The content of the amorphous substance of solifenacin and / or the amorphous substance of the salt thereof in the pharmaceutical composition is measured by high performance liquid chromatography. Further, when the pharmaceutical composition of the present invention is formulated into a tablet and the nuclear particles, the drug substance layer covering the nuclear particles, and the coating layer covering these are provided, the "mass of the entire pharmaceutical composition" of the present invention. May be "the mass of the entire formulation including all of the nuclear particles, the drug substance layer and the coating layer".

In the present specification, the “nuclear particles” refer to the particles that become the core of the tablet, and known components can be appropriately used depending on the purpose. For example, crystalline cellulose and purified sucrose spherical granules. , Carmelose sodium and the like can be used. Further, the "drug layer" is a copolymer having "an amorphous substance of solifenacin and / or an amorphous substance thereof and a vinyl alcohol and / or ethylene glycol as a constituent monomer (hereinafter, the present specification). Refers to a layer composed of "composition containing" (sometimes abbreviated as "copolymer"). The coating of the nuclei particles with the drug substance layer can be performed by dissolving the components constituting the drug substance layer in a solvent, then spraying the nuclei particles and drying them. Further, a protective layer for protecting the nuclear particles may be provided between the nuclear particles and the drug substance layer. The protective layer refers to, for example, a layer for protecting nuclear particles from gelation due to water or the like, and in such a case, the protective layer can be composed of talc, hydroxypropylmethyl cellulose or the like. The coating layer refers to the outermost layer of the tablet covering the drug substance layer, and the same coating layer as that described in detail later can be used. For example, the coating layer masks the bitterness of solifenacin. When used as a masking layer, the coating layer can be made of ethyl cellulose, hydroxypropyl methyl cellulose, or the like.

The pharmaceutical composition of the present invention may contain a crystal of solifenacin and / or a crystal of a salt thereof in addition to an amorphous body of solifenacin and / or an amorphous substance thereof. It is preferable that the amount of the amorphous substance is small and the amount of the amorphous substance is large. More specifically, the amorphous body of soriphenacin and / or the amorphous body of soriphenacin and / or the amorphous body of the salt thereof with respect to the total content of the amorphous body of soriphenacin and / or the crystalline body of the salt thereof. / Or the content of the amorphous body of the salt thereof is preferably more than 77% by mass, more preferably 80% by mass or more, further preferably 85% by mass or more, and 90% by mass or more. Is even more preferably 95% by mass or more, 99% by mass or more is particularly preferable, and 99.5% by mass or more is most preferable. In the present invention, the ratio of the amorphous body of solifenacin and / or the amorphous body of the salt thereof to the crystal body of solifenacin and / or the crystal body of the salt thereof is measured by an X-ray diffraction method.

The pharmaceutical composition of the present invention contains a copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer. It is presumed that the reason why the copolymer in the present invention improves the stability of the amorphous form of solifenacin by having vinyl alcohol and / or ethylene glycol as a constituent monomer is as follows. That is, it is generally known that when a polymer is used to maintain a drug or the like in an amorphous state, the higher the glass transition point of the polymer used, the easier it is to maintain the amorphous state. However, although polyvinyl alcohol, polyethylene glycol, graft copolymer and the like have a relatively low glass transition point, they unexpectedly showed an effect of maintaining solifenacin succinate (drug) in an amorphous state. The reason for improving the stability of the amorphous body of soriphenacin is that when the drug forms the crystal nucleation precursor, the polymer is incorporated into the crystal nucleation precursor and the transfer from the crystal nucleation precursor to the crystal nuclei is suppressed. This is because (increases the activation energy required for transition), probably because the hydrophobic and hydrophilic balance between the drug and the polymer is close, and the combination is easy to interact with by functional groups and the like. Is guessed.

The copolymer (copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer) contained in the pharmaceutical composition of the present invention is, for example, alkylene glycol (when the copolymer in the present invention has vinyl alcohol). It is preferable to have ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, etc.) as a monomer. When the copolymer in the present invention has ethylene glycol, it has an alkenyl alcohol (ethenyl group, 1-propenyl group, 2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group and the like. Alcohol), alkynyl alcohol (alcohol having an alkynyl group such as ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group) and the like are preferably used as monomers. The copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer is particularly preferably vinyl alcohol-polyethylene glycol-graft copolymer.

The copolymer (copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer) contained in the pharmaceutical composition of the present invention preferably has both vinyl alcohol and ethylene glycol as constituent monomers. .. The mass ratio of the monomer of vinyl alcohol and ethylene glycol is not particularly limited, but is preferably 1: 0.01 to 10, more preferably 1: 0.1 to 2, and 1: 0.15. It is more preferably to 1 and particularly preferably 1: 0.3 to 0.5.

The weight average molecular weight of the copolymer (copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer) contained in the pharmaceutical composition of the present invention is preferably 5000 to 100,000 Da, preferably 1000 to 80,000 Da. More preferably, it is more preferably 20000 to 60,000 Da, and particularly preferably 40,000 to 50,000 Da.

The copolymer (copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer) in the present invention may be, for example, a random copolymer, an alternate copolymer, a block copolymer, or the like, but the block copolymer may be used. It is preferably a polymer, and in particular, a graft copolymer.

The active component of the copolymer (copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer) contained in the pharmaceutical composition of the present invention (amorphous form of soriphenacin and / or an amorphous form of a salt thereof). The amount with respect to 100 parts by mass is not particularly limited, but is preferably 2 to 500 parts by mass with respect to 100 parts by mass of the active ingredient (amorphous form of soriphenacin and / or an amorphous form of a salt thereof). It is particularly preferable that the amount is ~ 300 parts by mass.

The viscosity of the copolymer (copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer) in the present invention is preferably, for example, a 20% by mass aqueous solution having a viscosity at 23 ° C. of 100 to 500 mPa · s. , 120 to 450 mPa · s is more preferable, 150 to 350 mPa · s is further preferable, 170 to 300 mPa · s is even more preferable, and 200 to 270 mPa · s is particularly preferable. In the present invention, the viscosity of the 20% by mass aqueous solution of the copolymer at 23 ° C. is measured according to EN ISO 2555 by measuring the viscosity of the 20% by mass aqueous solution at 23 ° C. with a shearing force of 100 rpm.

An amorphous substance of soriphenacin and / or a salt thereof contained in the pharmaceutical composition of the present invention and the above-mentioned copolymer (a copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer). The mass ratio is not particularly limited, but is more preferably 1: 1 to 1:20, further preferably 1: 1 to 1:18, and even more preferably 1: 4 to 1:15. , 1: 6 to 1:12 is particularly preferable.

The pharmaceutical composition of the present invention preferably contains the form of a solid dispersion. The "solid dispersion" means a solid in which a drug is dispersed in a monomolecular form in an inert carrier. The solid dispersion in the present invention preferably uses the above-mentioned copolymer as an inert carrier.

The pharmaceutical composition of the present invention may be formulated. Examples of the dosage form when formulated include tablets, liquids, capsules, granules, powders and the like. The dosage form of the present invention is preferably tablets, and among the tablets, particularly Orally disintegrating tablets are preferred.

Additives may be added to the pharmaceutical composition of the present invention as appropriate for formulation. Examples of such additives include excipients, binders, disintegrants, lubricants, colorants, preservatives, antioxidants, acidulants, flavors, artificial sweeteners, surfactants and the like. The excipient is not particularly limited, and for example, crystalline cellulose, calcium hydrogen phosphate hydrate, lactose, sucrose, glucose, mannitol, silicon dioxide and the like can be used. The binder is not particularly limited, and examples thereof include ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyethylene glycol, polyvinyl alcohol, and polyvinylpyrrolidone. The disintegrant is not particularly limited, and examples thereof include carmellose sodium, carmellose calcium, croscarmellose sodium, carboxymethyl starch sodium, sodium starch glycolate and the like. The lubricant is not particularly limited, and examples thereof include magnesium stearate, talc, and silica. The colorant is not particularly limited, and examples thereof include yellow iron sesquioxide and red iron sesquioxide. The antioxidant is not particularly limited, and examples thereof include tocopherol acetate, sodium sulfite, sodium hydrogen sulfite, and ascorbic acid. The acidulant is not particularly limited, and examples thereof include malic acid and the like. The fragrance is not particularly limited, and examples thereof include menthol and lemon. The artificial sweetener is not particularly limited, and examples thereof include aspartame and stevia. The surfactant is not particularly limited, and examples thereof include sodium lauryl sulfate, polyoxyethylene sorbitan aliphatic ester, and the like.

Further, when the pharmaceutical composition of the present invention is made into a tablet, it may be a preparation having a coating for coating the tablet body. In this case, the tablet body may be the same as the pharmaceutical composition in the form of the tablet described above. As a component constituting the coating, a component used as a coating agent for conventional tablets can be used, and examples thereof include hydroxypropylmethyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, cellulose acetate phthalate, titanium oxide, talc, lactose and the like. However, it is not limited to these. These may be used alone or in combination of two or more.

The pharmaceutical composition of the present invention may or may not contain water, but it is preferable that the amount of water is small, for example, the content of water is 1.0 with respect to the mass of the entire pharmaceutical composition. It is preferably 0% by mass or less, more preferably 0.1% by mass or less, further preferably 0.01% by mass or less, and further preferably not containing water.

The method for administering the pharmaceutical composition of the present invention may be oral administration or parenteral administration (intravenous administration or the like), and can be appropriately selected depending on the dosage form of the pharmaceutical composition. The dose is appropriately selected from a conventionally known effective amount of solifenacin in consideration of the administration method, disease symptoms, age of the administration target, etc. For example, for adults, the active ingredient (amorphous solifenacin) Amorphous form of the bulk and / or its salt) may be administered in an amount of 0.01 to 100 mg / kg / day.

<Manufacturing method of pharmaceutical composition>
In the present invention, the above-mentioned method for producing a pharmaceutical composition can be produced, for example, by the following method.

Specific examples of the production method include (1) a method of mixing particles of a pharmaceutical composition as they are with sugars or sugar alcohols or a selected disintegrant and pressurizing and compressing them to form tablets, and (2) pharmaceuticals. By mixing the particles of the composition with sugar or sugar alcohols, selected disintegrants, etc. and granulating with a binder solution, and mixing with other appropriate tablet additives and compressing under pressure. Method for producing tablets, (3) A saccharide having a low moldability is mixed with particles of a pharmaceutical composition, and the mixture is sprayed with a saccharide having a high moldability as a binder to coat and / or granulate the mixture under low pressure compression molding. After that, there are various manufacturing methods such as humidification and drying to make tablets. In the case of an orally disintegrating tablet containing particles of a pharmaceutical composition, special consideration must be given to particle destruction, tablet hardness, disintegration property, content uniformity, etc., and the method for producing an orally disintegrating tablet Is not limited to the method described here, and any method such as a molding method, a wet molding and drying method, etc. may be adopted for tableting.

The production method of the pharmaceutical composition of the present invention is not particularly limited, but an example of a specific production method is shown below.
Ethyl cellulose (Etocell STD-7) is taken and dissolved in ethanol, and talc is suspended to prepare a waterproof membrane solution. Solifenacin succinate and polyvinyl alcohol-polyethylene glycol-graft copolymer are taken and dissolved in a mixed solution of ethanol and purified water to prepare a drug coating solution. Etocell STD-7 and TC-5E are taken and dissolved in a mixed solution of ethanol and purified water to prepare an outer layer solution.
Carmelose sodium is put into a rolling flow type coating granulator (manufactured by Paulek Co., Ltd .: MP-01 type), and the waterproof film solution is sprayed and coated while being stirred and flowed, and dried to prepare waterproof film coating particles. .. The waterproof film-coated particles are put into a rolling flow type coating granulator (MP-01 type), and the drug coating liquid is sprayed and coated while being stirred and flowed, and dried to prepare the drug coating particles.
Next, the drug-coated particles are put into a rolling fluid coating granulator (MP-01 type), and the outer layer solution is spray-coated and dried while stirring and flowing to obtain particles of the outer layer-coated pharmaceutical composition. it can.

<Method of improving the stability of solifenacin amorphous>
The present invention includes a method of improving the stability of an amorphous form of solifenacin.

The method of the present invention further contains a copolymer containing vinyl alcohol and / or ethylene glycol as a constituent monomer in a pharmaceutical composition containing an amorphous substance of solifenacin and / or an amorphous substance of a salt thereof. This is a method for improving the stability of the amorphous form of solifenacin and / or the amorphous form of a salt thereof.

The copolymer having an amorphous form of solifenacin and / or an amorphous form of a salt thereof, vinyl alcohol and / or ethylene glycol as a constituent monomer exemplifies the same as those in the above-mentioned pharmaceutical composition of the present invention. can do.

<Amorphous metal stability evaluation 1>
(Example 1)
2.0 g of solifenacin succinate was dissolved in 475.0 g of water in which 10.0 g of polyvinyl alcohol-polyethylene glycol-graft copolymer (KOLLICOAT® IR) was dissolved. 200.0 g of crystalline cellulose (grains) (Selfia CP102) was put into a rolling flow type coating granulator (manufactured by Paulek Co., Ltd .: MP-01 type), and the prepared liquid was sprayed, coated and dried while being stirred and flowed. The pharmaceutical composition according to Example 1 was prepared. The mass ratio of solifenacin succinate to polyvinyl alcohol-polyethylene glycol-graft copolymer in the pharmaceutical composition was 1: 5.

(Example 2)
1.0 g of solifenacin succinate was dissolved in 475.0 g of water in which 10.0 g of polyvinyl alcohol-polyethylene glycol-graft copolymer (KOLLICOAT® IR) was dissolved. 200.0 g of crystalline cellulose (grains) (Selfia CP102) is put into a rolling flow type coating granulator (manufactured by Paulek Co., Ltd .: MP-01 type), and the prepared liquid is sprayed, coated and dried while stirring and flowing. Then, the pharmaceutical composition according to Example 2 was prepared. The mass ratio of solifenacin succinate to polyvinyl alcohol-polyethylene glycol-graft copolymer in the pharmaceutical composition was 1:10.

(Example 3)
It was prepared in the same manner as in Example 1 above, and produced so that the mass ratio of solifenacin succinate to polyvinyl alcohol-polyethylene glycol-graft copolymer in the pharmaceutical composition was 1: 1.

(Example 4)
It was prepared in the same manner as in Example 1 above, and produced so that the mass ratio of solifenacin succinate to polyvinyl alcohol-polyethylene glycol-graft copolymer in the pharmaceutical composition was 1: 3.

(Comparative Example 1)
2.0 g of solifenacin succinate was dissolved in 475.0 g of water in which 10.0 g of hydroxypropyl methylcellulose (TC-5 (registered trademark) E) was dissolved. 200.0 g of crystalline cellulose (grains) (Selfia CP102) was put into a rolling flow type coating granulator (manufactured by Paulek Co., Ltd .: MP-01 type), and the prepared liquid was sprayed, coated and dried while being stirred and flowed. The pharmaceutical composition according to Comparative Example 1 was prepared. The mass ratio of solifenacin succinate to hydroxypropylmethylcellulose in the pharmaceutical composition was 1: 5.

(Comparative Example 2)
1.0 g of solifenacin succinate was dissolved in 475.0 g of water in which 10.0 g of hydroxypropyl methylcellulose (TC-5 (registered trademark) E) was dissolved. 200.0 g of crystalline cellulose (grains) (Selfia CP102) was put into a rolling flow type coating granulator (manufactured by Paulek Co., Ltd .: MP-01 type), and the prepared liquid was sprayed, coated and dried while being stirred and flowed. A pharmaceutical composition according to Comparative Example 2 was prepared. The mass ratio of solifenacin succinate to hydroxypropylmethyl cellulose in the pharmaceutical composition was 1:10.

(Evaluation)
The stability of the pharmaceutical compositions according to Examples 1 and 2 and Comparative Examples 1 and 2 was evaluated. First, the pharmaceutical compositions according to Examples 1 and 2 and Comparative Examples 1 and 2 were placed in aluminum bags with zippers and stored at 60 ° C. and 75% RH for 14 days. After storage, the crystalline state of solifenacin succinate and the amount of the main decomposition product in the pharmaceutical compositions according to Examples 1 and 2 and Comparative Examples 1 and 2 were evaluated. After storage, the crystalline state of solifenacin succinate in the pharmaceutical compositions according to Examples 1 and 2 and Comparative Examples 1 and 2 was evaluated by X-ray diffraction from the viewpoint of whether or not the amorphous form was maintained. However, when a peak specific to solifenacin was confirmed, it was evaluated as having partially changed to a crystal, and when it was a halo peak, it was evaluated as having maintained an amorphous state. The "main decomposition product amount" is the ratio (mass%) of the amount of the amorphous body of solifenacin succinate after storage to the amount of the amorphous body of solifenacin succinate at the start of storage. means. The "main decomposition product" means the decomposition product having the largest amount of decomposition among the decomposition products of the amorphous body of solifenacin succinate. The amount of the main decomposition product of the amorphous form of solifenacin succinate was measured by high performance liquid chromatography. The results are shown in Table 1 below.

As shown in Table 1, the pharmaceutical compositions of Comparative Examples 1 and 2 can maintain the amorphous form of solifenacin succinate, but the amount of the main decomposition product is large, and the stability against decomposition is high. So it wasn't good. On the other hand, the pharmaceutical compositions of Examples 1 to 4 all maintained the amorphous form, and the amount of the main decomposition product was low. From this, it was confirmed that the use of polyvinyl alcohol-polyethylene glycol-graft copolymer together with solifenacin succinate improves both the stability of maintaining the amorphous form and the stability against decomposition. .. In particular, by increasing the mass ratio of the content of solifenacin succinate to the content of polyvinyl alcohol-polyethylene glycol-graft copolymer from 1: 1 to 1:10 and increasing the amount of polyvinyl alcohol-polyethylene glycol-graft copolymer. It was found that the stability of the amorphous substance against decomposition was further improved.

Claims (6)

It contains an amorphous form of solifenacin and / or an amorphous form of a salt thereof, and a copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer .
Copolymer having a vinyl alcohol and / or ethylene glycol as a constituent monomer, a polyvinyl alcohol - polyethylene glycol - graft copolymer der Ru, pharmaceutical compositions. The pharmaceutical composition according to claim 1, wherein the amorphous substance of solifenacin and / or the amorphous substance of a salt thereof contains the form of a solid dispersion dispersed in the copolymer. The amorphous body of soriphenacin and / or a salt thereof with respect to the total content of the amorphous body of soriphenacin and / or the amorphous body of the salt thereof and the crystalline body of soriphenacin and / or the crystalline body of the salt thereof. The pharmaceutical composition according to claim 1 or 2, wherein the content of the amorphous substance in the above is more than 77% by mass. The invention according to any one of claims 1 to 3, wherein the mass ratio of the amorphous substance of solifenacin and / or the amorphous substance of a salt thereof to the copolymer is 1: 1 to 1:20. Pharmaceutical composition. The pharmaceutical composition according to any one of claims 1 to 4, wherein the dosage form is a tablet. In a pharmaceutical composition containing an amorphous form of solifenacin and / or an amorphous form of a salt thereof,
Further, it is a method for improving the stability of an amorphous substance of solifenacin and / or an amorphous substance of a salt thereof by containing a copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer .
The method, wherein the copolymer having vinyl alcohol and / or ethylene glycol as a constituent monomer is polyvinyl alcohol-polyethylene glycol-graft copolymer .