JP2016079102A - Solifenacin-containing formulation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solifenacin-containing formulation which has no bitter taste and the like at the time of taking without coating bitter taste masking agent, and can be obtained by a simple method, in formulations containing solifenacin or a pharmaceutically acceptable salt thereof.SOLUTION: The invention provides a solifenacin-containing formulation containing solifenacin or a pharmaceutically acceptable salt thereof, and a metal chloride; and a production method of solifenacin-containing formulation characterized by containing solifenacin or a pharmaceutically acceptable salt thereof, and a metal chloride.SELECTED DRAWING: None

Description

  The present invention relates to a solifenacin-containing preparation, such as an orally disintegrating tablet. More specifically, the present invention relates to a preparation containing solifenacin and a method for producing the same.

  Solifenacin has the following formula:

The chemical name is (R) quinuclidin-3-yl (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate. Solifenacin is also known as the free base form and the succinate form (solifenacin succinate), for example, solifenacin succinate is a bladder spasm that functions as a selective antagonist to the muscarinic M3 receptor, It is used as a treatment for symptoms of active bladder (for example, urgency of urine and increased frequency of urination that may occur in patients with overactive bladder syndrome (OAB)). In particular, the present compound has a higher selectivity for M3 receptors present in smooth muscle, glandular tissues and the like compared to M2 receptors present in the heart and the like, and as an M3 receptor antagonist with few side effects on the heart and the like. It is particularly useful as a preventive or therapeutic agent for urinary incontinence, frequent urination, chronic obstructive pulmonary disease, chronic bronchitis, asthma and rhinitis. Solifenacin is currently sold in Japan as a treatment for urgency, frequent urination and urge urinary incontinence in overactive bladder as Vesicare (registered trademark), VESicare (registered trademark) in the United States, and Vesicare (registered trademark) in Europe Has been. Also, solifenacin or a pharmaceutically acceptable salt thereof is known to have a unique bitter taste.

  On the other hand, in recent years, various dosage forms have been developed from the viewpoint of QOL (Quality of life). In particular, orally disintegrating tablets have been actively developed because they can be taken without requiring water and can be taken even by patients who are difficult to chew or swallow. However, when a drug having a bitter taste is formulated as an orally disintegrating tablet, it is necessary to take measures to prevent the bitter taste of the drug from being exposed to the oral cavity due to the nature of the tablet to be taken after being dissolved or dissolved with saliva water. .

  For example, in Patent Document 1, core particles containing a drug having a bitter taste, an intermediate layer containing two types of water-soluble components, an insolubilization accelerator and an insolubilizing substance, and the water penetration speed into the outermost layer are set. It is disclosed to prepare time-release particles containing a controlled water infiltration amount control layer and to use the particles in an orally disintegrating tablet. Here, by using an insolubilization accelerator and an insolubilizing substance in the intermediate layer, it is possible to cover the core particles with the intermediate layer that dissolves quickly after the lag time but does not dissolve for a certain period of time. By further covering a water infiltration control layer made of a water-insoluble substance, the infiltration rate of water into the preparation is suppressed, so that the temporary insolubilization of the intermediate layer proceeds slowly and a long lag time is formed. As a result, bitterness is masked.

  In Patent Documents 2 and 3, the drug-containing particles are compressed by coating them with a coating substance containing methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer and a water-soluble polymer substance. It is disclosed that it is possible to reduce drug release from the core after molding and to form a sufficient lag time without using an insolubilization accelerator.

Japanese Patent No. 4277904 JP 2010-83886 A JP 2010-265325 A

  However, in Patent Documents 1 to 3, depending on the drug or base selected, initial drug elution and subsequent release may not be sufficient. In any of the examples, since a plurality of coating layers are provided on the drug particles, the manufacturing is complicated, and there is still room for further improvement.

  An object of the present invention is to provide a solifenacin-containing preparation which is obtained by a simple method without feeling bitterness when taken in a preparation containing solifenacin or a pharmaceutically acceptable salt thereof.

  As a result of repeated studies to solve the above problems, the present inventors have found that the drug particles containing solifenacin or a pharmaceutically acceptable salt thereof can be coated with metal without coating a bitter masking agent. By simply blending and compressing the above chloride, the obtained preparation was found to have a bitter taste masked when taken, and the present invention was completed.

That is, the present invention relates to [1] to [2].
[1] A solifenacin-containing preparation comprising solifenacin or a pharmaceutically acceptable salt thereof and a metal chloride.
[2] A method for producing a solifenacin-containing preparation, comprising combining solifenacin or a pharmaceutically acceptable salt thereof and a metal chloride.

  The solifenacin-containing preparation of the present invention is excellent in bitterness masking and has an excellent effect that it can be easily produced.

  The solifenacin-containing preparation of the present invention is characterized by comprising a metal chloride in solifenacin or a pharmaceutically acceptable salt thereof.

  The preparation of the present invention can be obtained by adding a metal chloride to the drug without coating the drug particles containing solifenacin or a pharmaceutically acceptable salt thereof with a substance that suppresses bitterness. Surprisingly, it can mask the bitter taste of solifenacin or a pharmaceutically acceptable salt thereof.

  Solifenacin in the present invention has the structural formula as described above. Also, pharmaceutically acceptable salts of solifenacin include succinic acid, formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, fumaric acid, maleic acid, lactic acid, malic acid, citric acid, tartaric acid, carbonic acid, picric acid Acid addition salts or quaternary ammonium salts with organic acids such as methanesulfonic acid, ethanesulfonic acid, glutamic acid, or mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid Can be mentioned. Solifenacin or a pharmaceutically acceptable salt thereof can be synthesized according to a known method. In the present invention, for example, succinate of solifenacin is preferable as a pharmaceutical product.

  The content of solifenacin or a pharmaceutically acceptable salt thereof in the preparation of the present invention is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and further preferably 1.0% by mass or more. . Further, it is preferably 50% by mass or less, more preferably 40% by mass or less, and still more preferably 30% by mass or less.

  The content of solifenacin in one preparation is preferably 0.1 mg or more, more preferably 1.0 mg or more, and further preferably 2.5 mg or more. Moreover, Preferably it is 30 mg or less, More preferably, it is 20 mg or less, More preferably, it is 10 mg or less. In this specification, “one preparation” means 1 tablet for tablets, 1 capsule for capsules, 1 capsule for fine granules, powders and granules, and 1 case for liquids and syrups. Means a single dose unit.

  In addition, solifenacin or a pharmaceutically acceptable salt thereof may be a powder itself. For example, even if it is a particle consisting only of a drug as an active ingredient, the drug and one or more additives You may use as a particle | grain consisting of.

  The additive used for the drug particles is not particularly limited as long as it is pharmaceutically acceptable, and can be appropriately selected according to a known formulation technique. In the present invention, solifenacin or a pharmaceutically acceptable salt thereof. From the viewpoint of ensuring the stability of the composition, an amorphous form of solifenacin and a stabilizer can be used in combination. Therefore, solifenacin or a pharmaceutically acceptable salt thereof may be used after it is made amorphous. “Amorphous” or “amorphous” means that solifenacin or a pharmaceutically acceptable salt thereof has a crystallographically amorphous structure. The method for evaluating the crystal state is not particularly limited as long as the crystal structure can be identified. For example, a method such as powder X-ray diffraction (XRD), DSC measurement, NMR measurement, or near infrared spectroscopy Is mentioned. Specifically, when the evaluation is performed using the XRD method, it should be clarified because it varies somewhat depending on the measurement conditions. However, a specific peak derived from the solifenacin crystalline substance seen around 2θ = 10 ° is present. If it is not recognized, it can be determined to be amorphous.

  The method for amorphizing solifenacin or a pharmaceutically acceptable salt thereof is not particularly limited as long as it is a known method. Specifically, solifenacin or a pharmaceutically acceptable salt thereof and any additive (for example, starches such as mannitol, corn starch and potato starch, crystalline cellulose, light anhydrous silicic acid, magnesium metasilicate inorganic aluminate, etc. Salt, etc.) or after pulverization, solifenacin or a pharmaceutically acceptable salt thereof such as freeze-drying or spray-drying in any solvent (for example, water, methanol, ethanol, propanol, polyethylene glycol, acetone, etc.) ) And then drying again, solifenacin or a pharmaceutically acceptable salt thereof dissolved in any solvent (eg, water, methanol, ethanol, propanol, polyethylene glycol, acetone, etc.) The tow Starches such as Rokoshidenpun and potato starch, crystalline cellulose, although a method of adsorbing the like in an inorganic salt or the like), such as light anhydrous magnesium silicate or metasilicate aluminate, and the like.

  The stabilizer is not particularly limited as long as it is pharmaceutically acceptable, and can be appropriately selected according to a known formulation technique. However, a more stable solifenacin or an amorphous form of a pharmaceutically acceptable salt thereof can be used. From the viewpoint of obtaining it, it is preferable to use one or more selected from the group consisting of malic acid or a pharmaceutically acceptable salt thereof and meglumine or a pharmaceutically acceptable salt thereof. In the present specification, “malic acid or a pharmaceutically acceptable salt thereof” and “meglumine or a pharmaceutically acceptable salt thereof” may be collectively referred to as an amorphous body maintenance agent. .

  As malic acid, neither L body nor D body is particularly limited. The pharmaceutically acceptable salt of malic acid is not particularly limited, and specific examples include sodium malate, disodium malate, calcium malate and the like. In addition, a malic acid derivative may be used as long as the effects of the present invention are not impaired.

  Meglumine or a pharmaceutically acceptable salt thereof is not particularly limited, and specific examples include meglumine and meglumine hydrochloride.

  The content of the amorphous body maintenance agent is preferably 1 part by mass or more, more preferably 10 parts by mass or more, and still more preferably 50 parts by mass or more with respect to 100 parts by mass of solifenacin or a pharmaceutically acceptable salt thereof. More preferably, it is 100 parts by mass or more. Moreover, although an upper limit is not set in particular, 1000 mass parts or less are preferable. In the present specification, the content of the amorphous body maintenance agent means the total content when a plurality of amorphous body maintenance agents are used.

  Further, the content of the amorphous body maintenance agent in the drug particles is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and further preferably 1% by mass or more. Further, it is preferably 90% by mass or less, more preferably 80% by mass or less, and still more preferably 50% by mass or less.

  In the case of using the amorphous body maintenance agent, an adsorbent can be further blended in order to ensure more stability. By containing the adsorbent, solifenacin or a pharmaceutically acceptable salt thereof and the amorphous body maintenance agent can be efficiently contacted, and as a result, the stability is further improved and the productivity is improved. .

  The adsorbent is not particularly limited as long as it is pharmaceutically acceptable, and can be appropriately selected according to a known preparation technique. Specifically, for example, calcium silicate, mannitol, partially pregelatinized starch, crystalline cellulose, soft anhydrous silicic acid, magnesium aluminate metasilicate, and the like may be used alone or in combination of two or more. It may be used. Of these, calcium silicate, mannitol, partially pregelatinized starch, crystalline cellulose, and magnesium aluminate metasilicate are preferred.

  The content of the adsorbent is preferably 1 part by mass or more, more preferably 50 parts by mass or more, and still more preferably 100 parts by mass or more with respect to 100 parts by mass of solifenacin or a pharmaceutically acceptable salt thereof. Moreover, although an upper limit is not set in particular, 1000 mass parts or less are preferable. In the present specification, the content of the adsorbent means the total content when a plurality of adsorbents are used.

  Further, the content of the adsorbent in the drug particles is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and further preferably 1.0% by mass or more. Further, it is preferably 90% by mass or less, more preferably 80% by mass or less, and still more preferably 50% by mass or less.

  Furthermore, when using the amorphous body maintenance agent, a binder can be further blended in addition to the adsorbent. By containing the binder, the contact of solifenacin or a pharmaceutically acceptable salt thereof and the amorphous body maintenance agent can be maintained. As a result, the amorphous state of solifenacin or a pharmaceutically acceptable salt thereof can be maintained over time. Any additive that can provide such an effect can be used as a binder in the present invention.

  The binder is not particularly limited as long as it is pharmaceutically acceptable, and can be appropriately selected according to a known preparation technique. Specifically, for example, water-soluble polymers such as polyvinylpyrrolidone, hypromellose, pullulan, methylcellulose, hydroxypropylcellulose, ethylcellulose, macrogol, polyvinyl alcohol, methacrylic acid copolymer, pregelatinized starch, starches, agar, etc. And sugar alcohols such as mannitol and the like, and these may be used alone or in combination of two or more. Of these, polyvinylpyrrolidone, hypromellose, pullulan and methylcellulose are preferable.

  In one aspect of the present invention, when the amorphous body maintenance agent is malic acid or a pharmaceutically acceptable salt thereof, the preferred binder is hypromellose, and the amorphous body maintenance agent is meglumine or When it is a pharmaceutically acceptable salt, a preferred binder is polyvinylpyrrolidone, pullulan or methylcellulose, and a more preferred binder is polyvinylpyrrolidone or methylcellulose.

  The content of the binder is preferably 1 part by mass or more, more preferably 10 parts by mass or more, and still more preferably 20 parts by mass or more with respect to 100 parts by mass of solifenacin or a pharmaceutically acceptable salt thereof. Moreover, although an upper limit is not set in particular, 1000 mass parts or less are preferable. In the present specification, the content of the binder means the total content when a plurality of binders are used.

  Further, the content of the binder in the drug particles is preferably 0.1% by mass or more, more preferably 0.2% by mass or more, and further preferably 0.5% by mass or more. Further, it is preferably 40% by mass or less, more preferably 35% by mass or less, and further preferably 25% by mass or less.

  The mass ratio of the adsorbent to the binder in the drug particles (adsorbent / binder) is preferably 1/100 or more, more preferably 1/10 or more, and even more preferably 1/1 or more. Further, it is preferably 1000/1 or less, more preferably 100/1 or less, and still more preferably 10/1 or less.

  Examples of additives used for drug particles other than the above components include excipients, disintegrants, binders, lubricants, sweeteners, acidulants, fragrances, fluidizing agents, colorants, and amorphous Stabilizers other than the mass maintaining agent, foaming agents, buffering agents, antioxidants, surfactants and the like can be mentioned. Moreover, it is also possible to use a well-known bitterness masking agent within the range which does not impair the effect of this invention.

  Examples of the excipient include saccharides such as dextran, dextrin, glucose, powdered sugar, and lactose, starches such as corn starch, and sugar alcohols such as crystalline cellulose and mannitol.

  Examples of the disintegrant include starches such as corn starch, partially pregelatinized starch, carmellose, carmellose calcium, croscarmellose sodium, crospovidone, and low-substituted hydroxypropylcellulose.

  Examples of the binder include hydroxypropyl cellulose, hypromellose, methyl cellulose, pregelatinized starch, polyvinyl pyrrolidone, and polyvinyl alcohol.

  Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated oil, sodium stearyl fumarate, sucrose fatty acid ester and the like.

  Sweeteners include, for example, sugars and sugar alcohols such as sucrose, fructose, maltose, sucrose, glucose, fructose, isomerized liquid sugar, fructooligosaccharides, cyclic oligosaccharides, saccharin sodium, dipotassium glycyrrhizin, aspartame, stevia, Examples include thaumatin.

  Examples of the sour agent include benzoic acid and its derivatives, tartaric acid, ascorbic acid and the like.

  Examples of the fragrances include menthol, orange extract, camphor, and vanillin.

  Examples of the fluidizing agent include silicon dioxides, magnesium aluminate metasilicate, and talc.

  Examples of the colorant include yellow ferric oxide, ferric oxide, iron oxide, titanium oxide, yellow No. 5, blue No. 1, yellow No. 4, red No. 2, red No. 3, red No. 102, copper chlorophyll, and the like. Can be mentioned.

  Examples of the stabilizer other than the amorphous body maintaining agent include citric acid or a salt thereof, sodium pyrosulfite, ascorbic acid, sodium bisulfite, sodium sulfite, benzoic acid or a salt thereof, EDTA, and the like.

  Examples of the foaming agent include sodium bicarbonate and sodium carbonate.

  Examples of the buffer include citric acid, sodium citrate, sodium hydrogen carbonate, sodium carbonate, sodium hydrogen phosphate, sodium dihydrogen phosphate and the like.

  Examples of the antioxidant include tocopherol, hydroquinone, sodium hydrogen sulfite, sodium sulfite, butylhydroxyanisole and the like.

  Examples of the surfactant include macrogol, polysorbate, polyoxyethylene hydrogenated castor oil, and sodium lauryl sulfate.

  These additives can be used individually by 1 type or in combination of 2 or more types, The usage-amount can be set suitably.

  The drug particles in the present invention can be granulated according to a known technique as long as they contain solifenacin or a pharmaceutically acceptable salt thereof. For example, solifenacin or a pharmaceutically acceptable salt thereof, or a mixture obtained by mixing an additive with solifenacin or a pharmaceutically acceptable salt thereof is extruded granulation method, rolling granulation method, fluidized bed granulation method. Granulation can be performed by a granulation method such as a granulation method, a spray-drying granulation method, or a crushing granulation method. Here, a solvent can be used as long as it does not impair the effects of the present invention. Specifically, for example, purified water, methyl alcohol, ethyl alcohol, propyl alcohol and the like can be used. Moreover, as an apparatus used, if it is a well-known stirring granulator or a fluid bed granulator, it can be used without limitation, The conditions can also be set suitably. If necessary, drying, sizing and sizing can be performed.

Although there is no restriction | limiting in particular as a particle diameter of a drug particle, From a viewpoint of handling, such as subsequent compression molding, capsule filling, packaging, etc., 20 micrometers or more are preferable, 50 micrometers or more are more preferable, and 100 micrometers or more are further more preferable. Moreover, 2000 micrometers or less are preferable, 1000 micrometers or less are more preferable, and 500 micrometers or less are more preferable. In the present specification, the particle diameter of the particle means a volume median particle diameter (D ₅₀ ), and can be measured by, for example, a laser diffraction particle size distribution measuring apparatus.

  Thus, drug particles containing solifenacin or a pharmaceutically acceptable salt thereof can be obtained, and this may be blended with a metal chloride.

  As the metal chloride, for example, sodium chloride, potassium chloride, and magnesium chloride can be used. These can be used if they are pharmaceutically acceptable. Of these, sodium chloride and / or potassium chloride is preferable.

  The content of the metal chloride is not particularly limited as long as it has the effect of the present invention. For example, it is preferably 1 part by mass or more with respect to 100 parts by mass of solifenacin or a pharmaceutically acceptable salt thereof. Is 10 parts by mass or more, more preferably 100 parts by mass or more, and still more preferably 200 parts by mass or more. Moreover, Preferably it is 2000 mass parts or less, More preferably, it is 1000 mass parts or less, More preferably, it is 500 mass parts or less. In the present specification, the content of metal chloride means the total content when a plurality of metal chlorides are used.

  Further, the content of the metal chloride in the preparation is not particularly limited as long as it has an effect of the present invention. For example, it is preferably 0.1% by mass or more, more preferably 0.5% by mass or more. More preferably, it is 1% by mass or more. Moreover, it is preferably 20% by mass or less, more preferably 15% by mass or less, and still more preferably 10% by mass or less.

  The preparation of the present invention may contain other additives in addition to the drug and metal chloride. Examples of other additives include the same additives as those used for the above-described drug particles, and can be appropriately selected according to a known formulation technique. Moreover, those usage-amounts can be set suitably.

  The preparation of the present invention can be prepared by adding a metal chloride to the drug, and can be prepared according to a known formulation technique according to the dosage form of the preparation of the present invention.

  The dosage form of the preparation of the present invention includes tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, jelly-like drops, etc.), capsules (including hard capsules and soft capsules), fine granules And dosage forms that can be administered as oral preparations such as powders, granules, liquids, syrups and the like. Of these, orally disintegrating tablets are preferred. The orally disintegrating tablet in the present invention may be rapidly disintegrated when the tablet is included in the oral cavity, and the specific disintegration time is within 3 minutes after being included in the oral cavity, preferably 1 Within minutes, more preferably within 30 seconds.

  For example, when the preparation of the present invention is an orally disintegrating tablet, it is prepared by mixing directly with raw materials containing other additives, if necessary, in addition to the drug particles and metal chloride, and then directly compressing the tablet. be able to. Moreover, it can prepare according to the method etc. which are described in patent gazette 4601271, patent publication gazette 2006-282551, patent publication gazette 2010-531841, etc. The apparatus to be used can be used without particular limitation as long as it is a known tableting machine, and the conditions can be set as appropriate. If necessary, humidification, drying, and coating can be performed.

  When the preparation of the present invention is, for example, an orally disintegrating tablet, it has disintegration property in the oral cavity and hardness sufficient to maintain the shape of the preparation when handled in the manufacturing process, distribution process, medical field, etc. There must be. The hardness is, for example, preferably 30 N or more, more preferably 40 N or more, still more preferably 50 N or more. In addition, although the hardness of the tablet in this invention can be measured using a tablet hardness meter, since it fluctuates with a tablet diameter and thickness, it is not limited to the said range.

  The preparation of the present invention can be suitably used for the treatment of urinary urgency, frequent urination, urge urinary incontinence, etc. in overactive bladder. Thus, it is appropriately determined according to individual cases. As an example, when solifenacin succinate is used as an active ingredient, the dose of the active ingredient per adult is usually about 0.01 to 100 mg / kg / day, which is divided into 1 or 2 to 4 times. Can be administered. In addition, water is not required for taking, but it may be taken as needed.

  Moreover, as one embodiment of the present invention, there is provided a method for producing a solifenacin-containing preparation comprising a step of blending a metal chloride with a drug containing solifenacin or a pharmaceutically acceptable salt thereof. In addition, the raw material and apparatus used here, and the preparation method are prescribed | regulated similarly to the above.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples. In this embodiment, the room temperature is 25 ° C.

Test example 1
After dissolving 30 g of solifenacin succinate in 15 g of purified water, 9 g of polyvinylpyrrolidone (PVP K90, manufactured by BASF) as a binder is dissolved in 54 g of purified water and mixed as an amorphous body maintaining agent. To a mixture of 60 g of meglumine and 30 g of calcium silicate as an adsorbent (FLORITE (registered trademark) RE, manufactured by Tokuyama Corporation), a stirring granulator (high speed mixer, LFS-GS-2J, manufactured by Fukae Kogyo Co., Ltd.) The mixture was stirred and granulated. The obtained granulated product was dried and sized (32 mesh).

  Next, 54 g of the obtained granulated product was mixed with 182 g of Mannit-P (manufactured by Mitsubishi Foodtech) and 111.8 g of Parteck Delta M (manufactured by MERCK), and then polyvinylpyrrolidone (PVP K30, manufactured by BASF) 7.5 A solution obtained by dissolving g in 150 g of purified water was granulated by spraying and stirring using a fluidized bed granulator (MP-01, manufactured by POWREC). The conditions were an air supply of 65 ° C and an exhaust of 35 ° C. The obtained granulated product was dried and sized (24 mesh) (particle size of the granulated product was 180 μm).

  Further, after 14.2 g of the obtained granulated product was mixed with 1.4 g of bitterness masking agent shown in Table 1, 0.5 g of Kollidon CL-F (BASF), 0.15 g of Aerosil 200 (Nippon Aerosil), What further mixed 0.15 g of magnesium stearate vegetable (Taipei Chemical Co., Ltd.) was tableted at 200 kgf using an oil press (HANDTAB-200, Ichibashi Seiki Co., Ltd.), and the mass per tablet was 164 mg of orally disintegrating tablets were obtained (solifenacin succinate content 5 mg, bitterness masking agent content 14 mg per tablet).

  The obtained tablets were subjected to a well-trained subject to evaluate the presence or absence of bitterness during oral disintegration. The results are shown in Table 1.

  Table 1 shows that bitterness is suppressed only when sodium chloride and potassium chloride are used as a bitterness masking agent.

  As described above, by adding sodium chloride to solifenacin-containing granules, it was possible to design a formulation that does not feel the bitterness unique to solifenacin.

  The solifenacin-containing preparation of the present invention suppresses the bitter taste of solifenacin and can be produced by a simple technique.

Claims (12)

  A solifenacin-containing preparation comprising solifenacin or a pharmaceutically acceptable salt thereof and a metal chloride.   The preparation according to claim 1, wherein the content of the metal chloride is 1 to 2000 parts by mass with respect to 100 parts by mass of solifenacin or a pharmaceutically acceptable salt thereof.   The preparation according to claim 1 or 2, wherein the metal chloride comprises sodium chloride and / or potassium chloride.   Furthermore, any one of Claims 1-3 which comprise 1 type, or 2 or more types selected from the group which consists of malic acid or its pharmaceutically acceptable salt, and meglumine or its pharmaceutically acceptable salt. 2. The preparation according to item 1.   The content of one or more selected from the group consisting of malic acid or a pharmaceutically acceptable salt thereof and meglumine or a pharmaceutically acceptable salt thereof is solifenacin or a pharmaceutically acceptable salt thereof The preparation according to claim 4, which is 1-1000 parts by mass with respect to 100 parts by mass.   The preparation according to any one of claims 1 to 5, further comprising an adsorbent.   The preparation according to claim 6, wherein the adsorbent comprises one or more selected from the group consisting of calcium silicate, mannitol, partially pregelatinized starch, crystalline cellulose, and magnesium aluminate metasilicate.   The preparation according to claim 6 or 7, further comprising a binder.   The preparation according to claim 8, wherein the binder comprises one or more selected from the group consisting of polyvinylpyrrolidone, hypromellose, pullulan and methylcellulose.   The preparation according to any one of claims 1 to 9, wherein the dosage form is selected from the group consisting of tablets, capsules, fine granules, powders, granules, liquids, and syrups.   The formulation in any one of Claims 1-10 whose dosage form is an orally disintegrating tablet.   A method for producing a solifenacin-containing preparation, comprising combining solifenacin or a pharmaceutically acceptable salt thereof and a metal chloride.