Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/1605—Excipients; Inactive ingredients
  • A61K9/1611—Inorganic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/1605—Excipients; Inactive ingredients
  • A61K9/1629—Organic macromolecular compounds
  • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P11/00—Drugs for disorders of the respiratory system
  • A61P11/02—Nasal agents, e.g. decongestants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P11/00—Drugs for disorders of the respiratory system
  • A61P11/06—Antiasthmatics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/08—Antiallergic agents

Definitions

• the present invention relates to a solid preparation containing a dibenzo [b, e] oxepin derivative and having excellent storage stability such as light stability.
• A represents a single bond, —CH ⁇ CH— or (CH 2 ) n — (wherein n represents an integer of 1 to 3), and R 1 and R 2 are the same or different and represent hydrogen.
• a lower alkyl, or a dibenzo [b, e] oxepin derivative represented by the above or a pharmaceutically acceptable salt thereof (hereinafter referred to as compound ( I)) has anti-allergic and anti-inflammatory effects and is known to be useful for allergic rhinitis, allergic diseases such as asthma and skin diseases such as urticaria (Japanese Patent Laid-Open No. 63-10784).
• a stabilized solid preparation can be obtained by adding a cellulose derivative such as croscarmellose sodium to the sugar- and cellulose-based compound (I) or a pharmacologically acceptable salt-containing preparation thereof. It is known (see Patent Document 1).
• Compound (I) or a pharmaceutically acceptable salt thereof is known to be unstable by light, and is excellent in storage stability such as light stability by applying a film coating containing a light-shielding agent.
• Known solid preparations and the like are also known.
• dry syrup which is one of quick disintegrating preparations
• dry syrup is a “preparation used by dissolving or suspending at the time of use” and is preferably dissolved or disintegrated rapidly and suspended when added to water.
• Orally disintegrating tablets are required to dissolve or disintegrate rapidly in the oral cavity with saliva or a small amount of water.
• fast disintegrating preparations such as dry syrup and orally disintegrating tablets
• film coating is applied to the surface of the preparation, dissolution or disintegration of the preparation may be delayed, and a coating is provided on the surface of the solid preparation. It is desirable to stabilize the light-labile active ingredient contained in the preparation.
• a film coating containing a light-shielding agent is used on the surface of a solid preparation.
• a film coating containing a light-shielding agent is used.
• it is insensitive to the light contained in the preparation even when the surface of the solid preparation is not provided with a film coating.
• An object of the present invention is to provide a solid preparation containing compound (I) or a pharmaceutically acceptable salt thereof and having excellent storage stability such as light stability.
• the present invention relates to the following (1) to (9).
• Compound (I) a lower alkyl, or a dibenzo [b, e] oxepin derivative (hereinafter referred to as Compound (I)) or a pharmaceutically Containing an acceptable salt, (ii) iron oxide, and (iii) a drug-containing granule containing one or more selected from sugar, starch, starch derivative, cellulose, cellulose derivative and sugar alcohol, A solid preparation in which (i) to (iii) are mixed. (2) further comprising (iv) iron oxide, and (v) an iron oxide-containing part containing one or more selected from sugar, starch, starch derivatives, cellulose, cellulose derivatives and sugar alcohols, (Iv) and (v) are mixed in the solid preparation according to the above (1).
• the drug-containing granule is one or more selected from the dibenzo [b, e] oxepin derivative or a pharmaceutically acceptable salt thereof, iron oxide, and sugar, starch, starch derivative, cellulose, cellulose derivative and sugar alcohol.
• the amount of iron oxide in the drug-containing granule is 0.01 to 1 part by mass with respect to 1 part by mass of the dibenzo [b, e] oxepin derivative or pharmaceutically acceptable salt thereof in the drug-containing granule.
• the amount of iron oxide contained in the solid preparation is 0.01 to 6 parts by mass with respect to 1 part by mass of the dibenzo [b, e] oxepin derivative or pharmaceutically acceptable salt thereof in the drug-containing granules.
• the amount of the dibenzo [b, e] oxepin derivative or pharmaceutically acceptable salt thereof in the drug-containing granule is 0.1 to 30 parts by mass with respect to 100 parts by mass of the drug-containing granule.
• a solid preparation containing compound (I) or a pharmaceutically acceptable salt thereof and excellent in storage stability such as light stability can be provided.
• the solid preparation of the present invention is selected from (i) compound (I) or a pharmaceutically acceptable salt thereof, (ii) iron oxide, and (iii) sugar, starch, starch derivative, cellulose, cellulose derivative and sugar alcohol.
• the drug-containing granule containing one or more of the above, and (i) to (iii) are mixed in the drug-containing granule.
• the drug-containing granules obtained by granulating (i) to (iii) are preferred as the drug-containing granules, and the drug-containing granules obtained by mixing (i) to (iii) at once and then granulating them.
• the solid preparation of the present invention contains (iv) iron oxide, and (v) an oxidation containing one or more selected from sugar, starch, starch derivatives, cellulose, cellulose derivatives and sugar alcohols.
• An iron-containing part is preferably contained, and (iv) and (v) are preferably mixed in the iron oxide-containing part.
• the iron oxide-containing part is obtained by granulating the iron-containing part or (iv) and (v) obtained by powder-coating the drug-containing granules in the present invention with (iv) and (v).
• the resulting iron oxide-containing part is preferred.
• the lower alkyl is, for example, a linear or branched alkyl having 1 to 6 carbon atoms, specifically methyl, ethyl, propyl Isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl and the like.
• the heterocyclic group formed together with the adjacent nitrogen atom include pyrrolidinyl, morpholino, thiomorpholino, N-methylpiperazinyl, pyrazolidinyl, piperidino, piperazinyl, indolyl, isoindolyl and the like.
• Examples of the pharmaceutically acceptable salt of compound (I) include pharmaceutically acceptable acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts, and the like.
• Examples of pharmaceutically acceptable acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, nitrate, sulfate, and phosphate, such as acetate, maleate, fumarate, and tartrate. And organic acid salts such as citrate.
• Examples of the pharmaceutically acceptable metal salt include alkali metal salts such as lithium salt, sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt and zinc salt.
• Examples of the pharmaceutically acceptable ammonium salt include salts such as ammonium and tetramethylammonium.
• examples of the pharmaceutically acceptable organic amine addition salt include addition salts such as morpholine and piperidine.
• Examples of pharmaceutically acceptable amino acid addition salts include addition salts of lysine, glycine, phenylalanine, aspartic acid, glutamic acid and the like.
• Compound (I) can be produced by the method disclosed in JP-A-63-10784 or according thereto.
• compounds in which A is CH 2 and R 1 and R 2 are both CH 3 are preferred, and preferred specific examples of compound (I) or a pharmaceutically acceptable salt thereof include compounds of the formula (A) And (Z) -11- (3-dimethylaminopropylidene) -6,11-dihydrodibenzo [b, e] oxepin-2-acetic acid hydrochloride (hereinafter referred to as compound (A)).
• the particle diameter of the compound (I) or a pharmaceutically acceptable salt thereof is preferably 5 to 150 ⁇ m, and preferably 20 to 120 ⁇ m, as measured by microscopy or sieving. More preferably, the thickness is 30 to 100 ⁇ m.
• the amount of compound (I) or a pharmaceutically acceptable salt thereof in the drug-containing granules in the present invention is preferably 0.1 to 30 parts by mass with respect to 100 parts by mass of the drug-containing granules, More preferably, it is ⁇ 20 parts by mass.
• the solid preparation of the present invention may contain other active ingredients in addition to the compound (I) or a pharmaceutically acceptable salt thereof.
• the iron oxide in the present invention is not particularly limited.
• iron sesquioxide Bengara, Fe 2 O 3
• yellow iron sesquioxide Fe 2 O 3 .H 2 O
• yellow iron oxide iron black iron oxide
• Preferred examples include iron sesquioxide, yellow iron sesquioxide, or a combination thereof.
• the total amount of iron oxide contained in the drug-containing granule in the present invention is 0.005 to 1 with respect to 1 part by mass of the compound (I) or a pharmaceutically acceptable salt thereof contained in the drug-containing granule.
• the amount is preferably part by mass, more preferably 0.01 to 0.5 part by mass, and still more preferably 0.03 to 0.1 part by mass.
• the total amount of iron oxide contained in the drug-containing granule is the compound (I ) Or its pharmaceutically acceptable salt amount is preferably 0.01 parts by mass or more per 1 part by mass.
• the total amount of iron oxide contained in the iron oxide-containing part of the present invention is 1 part by weight of the amount of the compound (I) or pharmaceutically acceptable salt thereof contained in the drug-containing granule of the present invention.
• the amount is preferably 0.005 to 5 parts by mass, more preferably 0.01 to 0.5 parts by mass, and still more preferably 0.03 to 0.2 parts by mass.
• the present invention contains the drug-containing granule according to the present invention and an iron oxide-containing part obtained by powder-coating (iv) and (v) on the drug-containing granule
• the total amount of iron oxide contained in the iron oxide-containing part is 0.01 parts by weight with respect to 1 part by weight of the compound (I) or a pharmaceutically acceptable salt thereof contained in the drug-containing granule in the present invention. If it is the above, it is not necessary to contain iron oxide in the drug-containing granule in the present invention.
• the total amount of iron oxide in the solid preparation of the present invention is 0.01 to 6 with respect to 1 part by mass of the compound (I) or a pharmaceutically acceptable salt thereof contained in the drug-containing granule in the present invention.
• the amount is preferably part by mass, more preferably 0.02 to 0.5 part by mass.
• the sugar in the present invention is not particularly limited, and examples thereof include monosaccharides, disaccharides, and oligosaccharides.
• monosaccharides include glucose, xylose, galactose, and fructose.
• disaccharide include trehalose, lactose, sucrose, maltose, palatinose and the like.
• oligosaccharide include raffinose, inulooligosaccharide (chicory oligosaccharide), palatinose oligosaccharide and the like.
• the sugar in the present invention may be an anhydride or a hydrate.
• lactose includes lactose hydrate and anhydrous lactose listed in the Japanese Pharmacopoeia.
• Preferred sugars in the present invention include lactose, sucrose, maltose or combinations thereof, and more preferably lactose, sucrose or combinations thereof.
• the starch in the present invention is not particularly limited, and examples thereof include corn starch, potato starch, rice starch, wheat starch, and combinations thereof.
• the starch derivative in the present invention is not particularly limited, and examples thereof include pregelatinized starch, partially pregelatinized starch, hydroxypropyl starch, sodium carboxymethyl starch and the like, or combinations thereof.
• the cellulose in the present invention is not particularly limited, and examples thereof include crystalline cellulose, powdered cellulose and the like, or combinations thereof.
• the cellulose derivative in the present invention is not particularly limited, and examples thereof include croscarmellose sodium, low-substituted hydroxypropyl cellulose, carmellose calcium and the like, or combinations thereof.
• the sugar alcohol in the present invention is not particularly limited, and examples thereof include mannitol, maltitol, erythritol, sorbitol, xylitol, and preferably mannitol, maltitol, erythritol, or a combination thereof.
• sugar, starch, starch derivatives, cellulose, cellulose derivatives and sugar alcohols more preferably lactose, sucrose, corn starch, potato starch, crystalline cellulose, croscarmellose sodium, low substituted hydroxypropyl cellulose,
• lactose sucrose, corn starch, potato starch, crystalline cellulose, croscarmellose sodium, low substituted hydroxypropyl cellulose
• carmellose calcium, hydroxypropyl starch, mannitol, maltitol and erythritol are mentioned, and more preferably lactose, sucrose, croscarmellose sodium, low-substituted hydroxypropylcellulose, carmellose calcium, hydroxypropyl
• starch and mannitol one or more selected from starch and mannitol.
• the drug-containing granule and the iron oxide-containing part in the present invention may contain other additives as desired. However, it is preferable not to contain titanium oxide.
• Other additives that may be contained in the drug-containing granules in the present invention include, for example, poorly water-soluble inorganic salts (for example, talc, light anhydrous silicic acid, sodium aluminate metasilicate, calcium silicate, calcium phosphate, etc.), binding Agents (for example, methylcellulose, carboxymethylcellulose, carboxypropylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, pullulan, dextrin, gum arabic, gelatin, etc.) and the like are used alone or in combination of two or more. May be.
• poorly water-soluble inorganic salts for example, talc, light anhydrous silicic acid, sodium aluminate metasilicate, calcium silicate, calcium phosphate, etc
• acidulants e.g., citric acid, tartaric acid, malic acid, etc.
• antioxidants e.g., tocopherol, ascorbic acid, cysteine hydrochloride, L-ascorbic acid stearate, etc.
• Coloring agents for example, food yellow No. 5, food red No. 2,
• the drug-containing granules in the present invention can be obtained, for example, by granulating a mixture containing (i) to (iii), or powder-coating the mixture onto core particles.
• the total amount of iron oxide contained in the mixture is preferably 0.05 to 1 part by mass, more preferably 0.1 to 0.5 part by mass with respect to 100 parts by mass of the mixture.
• the iron oxide-containing part in the present invention may be a mixture obtained by mixing (iv) and (v) .
• the mixture containing (iv) and (v) is granulated, or
• the mixture may be obtained by powder coating the drug-containing granules in the present invention.
• the total amount of iron oxide contained in the mixture is preferably 0.05 to 1 part by mass, more preferably 0.1 to 0.5 part by mass with respect to 100 parts by mass of the mixture.
• examples of the granulation method include a wet granulation method and a dry granulation method.
• examples of the wet granulation method include an extrusion granulation method (by a screw extrusion granulator, a roll extrusion granulator, etc.), a rolling granulation method (a rotating drum granulator, a centrifugal rolling granulator). Etc.), fluidized bed granulation method (by fluidized bed granulator, rolling fluidized bed granulator, etc.), stirring granulation method (by stirring granulator, etc.), etc., preferably stirring granulation The law is raised.
• the binder liquid is a liquid obtained by suspending or dissolving the binder in water or a pharmaceutically acceptable solvent, and the concentration of the binder in the binder liquid is the total mass of the binder liquid.
• the amount is preferably 0.1 to 50 parts by mass, more preferably 0.5 to 20 parts by mass with respect to 100 parts by mass.
• the core particles are rolled or agitated to flow the powder.
• a coating layer covering the core particles is formed by spraying or dropping water or the binder liquid onto the core particles while sprinkling the agent on the core particles with powder.
• the drug-containing granules in the present invention are obtained by, for example, powder-coating a mixture containing (i) to (iii) on the core particles, the core particles are granulated spherical seed particles and the like.
• the powder spray is a mixture containing (i) to (iii). Further, in the case where the iron oxide-containing part in the present invention is obtained by, for example, powder-coating the drug-containing granule in the present invention with a mixture containing (iv) and (v), the above-mentioned core particles are used in the present invention. It is a drug-containing granule, and the powder spray is a mixture containing (iv) and (v).
• the solid preparation of the present invention may have any shape as long as it can be administered orally, and examples thereof include powders, fine granules, granules, tablets and the like, and solids in the form of powder, fine granules or granules.
• Formulations include dry syrups, and solid formulations in the form of tablets include orally disintegrating tablets.
• the drug-containing granule in the present invention can be used as it is as a powder, fine granule or granule.
• the drug-containing granules in the present invention may be film coated to form a powder, fine granules or granules, but when it is a dry syrup in the form of a powder, fine granules or granules, Even when a film coating is not provided or a film coating is provided, it is preferable that a film coating that is very rapidly disintegrated or dissolved is applied.
• the drug-containing granule according to the present invention obtained by powder-coating the mixture containing (iv) and (v) to produce the iron oxide-containing part according to the present invention is used as it is, as a powder, fine granule or It can be a granule.
• the drug-containing granule according to the present invention is powder-coated with a mixture containing (iv) and (v) to produce the iron oxide-containing part according to the present invention. It may be a granule or a granule, but if it is a dry syrup in the form of a powder, fine granule or granule, it will not disintegrate even if it has no film coating or a film coating. Or it is preferable that the film coating which melt
• the drug-containing granule in the present invention alone or mixed with (iv) and (v) and optionally contained in the iron oxide-containing part in the present invention. It can be produced by a method of producing a tablet by mixing with other additives which may be good and compression molding with a tableting machine.
• the tablet may be produced by a method of producing a tablet in the same manner after film coating is applied to the drug-containing granule in the present invention.
• the tablet is an orally disintegrating tablet, the drug-containing granule may be produced.
• the granule has no film coating, or even if it has a film coating, it is film coated into a drug-containing granule that is small enough to be swallowed without water, or has disintegrated or dissolved. It is preferable that the film is subjected to fast film coating.
• the drug-containing granule according to the present invention is a powder-coated mixture containing (iv) and (v) to produce an iron oxide-containing part according to the present invention alone or as desired.
• One or more selected from starch derivatives, cellulose, cellulose derivatives and sugar alcohols, and other additives that may be contained in the iron oxide-containing part of the present invention are mixed and compression-molded with a tableting machine to produce tablets. It can also be manufactured by the following method.
• the tablet is produced by a method of producing a tablet in the same manner after coating the mixture containing (iv) and (v) by powder coating to produce the iron oxide-containing part in the present invention.
• the film coating is not provided, or even if it is provided with a film coating, it is small enough to be swallowed without water. It is preferable that the drug-containing granule is a film-coated one or a film coating that is rapidly disintegrated or dissolved.
• the drug-containing granule according to the present invention and the iron oxide-containing part according to the present invention obtained by granulating a mixture containing, for example, (iv) and (v) are mixed, and if desired, the sugar
• a mixture containing, for example, (iv) and (v) are mixed, and if desired, the sugar
• the sugar By mixing one or more selected from starch, starch derivatives, cellulose, cellulose derivatives and sugar alcohols and other additives that may be contained in the iron oxide-containing part in the present invention, and compression-molding with a tableting machine It can also be produced by a method for producing tablets.
• the tablet may be produced by the same method of producing a tablet after film coating is applied to the drug-containing granule in the present invention.
• the drug-containing granule may be produced.
• the granule does not have a film coating or is provided with a film coating, it is a film-coated granule that is small enough to be swallowed without water, or has disintegrated or dissolved. It is preferable that a fast film coating is applied.
• the tableting machine is not particularly limited, and for example, a tableting machine such as a rotary tableting machine or a hydraulic press machine can be used. Also, for example, a mortar coated with a trace amount of a lubricant such as stearic acid such as stearic acid, magnesium stearate, calcium stearate, or a metal salt thereof, sucrose fatty acid ester or glycerin fatty acid ester, hardened oil and fat in advance. You may use the tableting machine which has, and may manufacture a tablet using what is called an external lubrication compression molding method.
• a lubricant such as stearic acid such as stearic acid, magnesium stearate, calcium stearate, or a metal salt thereof, sucrose fatty acid ester or glycerin fatty acid ester, hardened oil and fat.
• the shape of the tablet is specifically preferably a round tablet, a triangular tablet, a cannonball tablet, or the like.
• the size of the tablet of the present invention is not particularly limited, but for example, it is preferably 0.1 to 2 g in mass and 0.3 to 2.0 cm in diameter.
• the tablet has a hardness that does not cause breakage, breakage, or the like.
• the hardness of the tablet is generally measured as a breaking strength in the diameter direction of the tablet with a tablet hardness tester, and the value is preferably 20 to 200N, more preferably 30 to 150N, and 40 to 100N. It is particularly preferred that The hardness of the tablet can be measured with a commercially available tablet breaking strength measuring machine such as TH-203CP type manufactured by Toyama Sangyo.
• Test example 1 10 g of the ingredients shown in Table 1 were mixed in a mortar until uniform.
• the photostability tests of the mixed powders obtained in A to E and comparisons a to c were performed under the following conditions. Each mixed powder was uniformly arranged on a petri dish, and irradiated with xenon lamp 30000 Lux light for 40 hours (1.2 million Lux ⁇ hour) in a constant temperature and humidity chamber maintained at 25 ° C./60% RH. After exposure, the amount of the related substance produced of compound (A) was determined by high performance liquid chromatography. The results are shown in Table 2.
• the related substance (B) is a geometric isomer of the compound (A), is generated by photoisomerization, and does not occur in a solid preparation under storage protected from light.
• CF-360 CF Granulator 360, manufactured by Freund Corporation, the same shall apply hereinafter
• 2000 g of purified sucrose spherical granules as core particles are sprayed with an aqueous hydroxypropyl cellulose solution (5.9% by weight).
• 23.6 g of compound (A) and a mixture (solid) of each additive in an amount according to the composition ratio shown in Table 3 were sprayed to obtain the drug-containing granules in the present invention.
• a solid preparation of the present invention was obtained in the same manner as in Example 1 except that the amount of additive according to the composition ratio shown in Table 3 was used.
• a solid preparation of the present invention was obtained in the same manner as in Example 1 except that the amount of additive according to the composition ratio shown in Table 3 was used.
• CF-360 CF Granulator 360, manufactured by Freund Corporation, the same shall apply hereinafter
• 2000 g of purified sucrose spherical granules as core particles are sprayed with an aqueous hydroxypropyl cellulose solution (5.9% by weight).
• 23.6 g of compound (A) and a mixture (solid) of each additive in an amount according to the composition ratio shown in Table 3 were powder-coated to obtain a drug-containing granule according to the present invention.
• a solid preparation of the present invention was obtained in the same manner as in Example 5 except that the amount of additive according to the composition ratio shown in Table 4 was used.
• a solid preparation of the present invention was obtained in the same manner as in Example 5 except that the amount of additive according to the composition ratio shown in Table 4 was used.
• Test example 2 The light stability of each solid preparation obtained in Examples 1 to 7 was evaluated. Each solid preparation (granule) is charged to a plastic petri dish to a thickness of 3 mm, and it is placed in a light stability tester (LTX-01, light source: xenon lamp) under the condition of 30000 Lux -25 °C / 60% RH Irradiated for 20 hours (600,000 Lux ⁇ hour) and 40 hours (1.2 million Lux ⁇ hour). After exposure, the production amount of the related substance of compound (A) was determined by high performance liquid chromatography in the same manner as in Test Example 1. The results are shown in Table 5.
• LTX-01 light source: xenon lamp
• a solid preparation containing compound (I) or a pharmaceutically acceptable salt thereof and excellent in storage stability such as light stability can be provided.

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• 2010
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