WO2012147873A1 - Composition d'enrobage présentant une dispersabilité orale supérieure - Google Patents

Composition d'enrobage présentant une dispersabilité orale supérieure Download PDF

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Publication number
WO2012147873A1
WO2012147873A1 PCT/JP2012/061265 JP2012061265W WO2012147873A1 WO 2012147873 A1 WO2012147873 A1 WO 2012147873A1 JP 2012061265 W JP2012061265 W JP 2012061265W WO 2012147873 A1 WO2012147873 A1 WO 2012147873A1
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WIPO (PCT)
Prior art keywords
water
tablet
trehalose
coating
coating composition
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PCT/JP2012/061265
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English (en)
Japanese (ja)
Inventor
雅裕 西村
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持田製薬株式会社
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Application filed by 持田製薬株式会社 filed Critical 持田製薬株式会社
Priority to JP2013512441A priority Critical patent/JP5690925B2/ja
Priority to PCT/JP2012/077576 priority patent/WO2013161103A1/fr
Priority to JP2014512292A priority patent/JP5690972B2/ja
Publication of WO2012147873A1 publication Critical patent/WO2012147873A1/fr

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    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/282—Organic compounds, e.g. fats
    • A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system

Definitions

  • the present invention relates to an outermost layer coating composition suitably used for forming a thin film as the outermost layer of various orally disintegrating tablets for pharmaceutical use, supplements, etc., an outermost layer coating liquid, and a coating having the outermost layer film It is related with a tablet and its manufacturing method.
  • Patent Document 1 discloses an orally disintegrating film-coated tablet including an orally disintegrating tablet core and a film coating layer. By providing such a film coating layer, an orally disintegrating tablet is disclosed. While maintaining the above characteristics, it is possible to provide a tablet having high strength that is stable against abrasion and impact at the time of manufacturing, transporting, storing, packaging, and dispensing.
  • a film made of a water-soluble polymer, a plasticizer (Macrogol 400) and titanium oxide is used as the film formed on the outside of the tablet.
  • a plasticizer Mocrogol 400
  • titanium oxide titanium oxide
  • problems such as a feeling of slimming and disintegration that are characteristic of film coating, delay of disintegration, and peeling of the tablet due to slight swelling of the tablet due to moisture absorption.
  • Patent Document 2 is mainly composed of a sugar coating layer containing 50 mg of ⁇ , ⁇ -trehalose, 10 mg of talc, 5 mg of precipitated calcium carbonate, 1.5 mg of gum arabic and 0.5 mg of gelatin per 252 mg of uncoated tablet, and sucrose.
  • a sugar-coated tablet is obtained by forming a top sugar-coated layer by a pan coating method.
  • Patent Document 3 discloses an undercoat solution comprising 40 parts by weight of water containing trehalose, 2 parts by weight of pullulan (average molecular weight 200,000), 30 parts by weight of water, 25 parts by weight of talc and 3 parts by weight of titanium oxide, and then water containing trehalose.
  • a coating method is disclosed in which an overcoat liquid comprising 65 parts by weight, 1 part by weight of pullulan and 34 parts by weight of water is used for the uncoated tablet.
  • the coating films disclosed in Patent Documents 2 and 3 are not intended for orally disintegrating tablets, and are further used in combination with a binder and are considered to have a layer thickness of several hundreds of ⁇ m or more. Whether it is possible to produce a coated tablet that maintains the above characteristics is unclear.
  • Patent Document 4 discloses a thin-layer sugar-coated tablet having a sugar-coated layer containing a sugar, an excipient, and a binder at 5 to 60% of the weight of the uncoated tablet. It is useful for masking unpleasant odors and preventing whisker generation, can be made sugar-free, has a short manufacturing time, can be downsized, and decomposes with high moisture due to low water content of tablets. It is said to be a thin-layer sugar-coated tablet that can stabilize the drug.
  • Example 2 a sugar coating solution in which 50 g of erythritol, 28 g of talc, 10 g of crystalline cellulose and 12 g of gum arabic powder were dissolved and suspended in 120 g of purified water was used in 300 g of uncoated tablets, and 35% of the uncoated tablet weight with respect to the uncoated tablets.
  • a sugar coating solution in which 89 g of erythritol, 10 g of gum arabic powder, and 1 g of macrogol 6000 were dissolved in 160 g of purified water was coated on the uncoated tablet in an amount of 5% to obtain a thin-layered sugar-coated tablet,
  • a thin layer of sugar-coated tablets is coated with a slight amount of a polishing liquid.
  • This sugar-coated film is not intended for orally disintegrating tablets, and it is also used as a thin-layered sugar-coated tablet.
  • the thickness is considered to be several hundred ⁇ m or more, and it is completely unknown whether a coated tablet that maintains the characteristics of an orally disintegrating tablet can be produced.
  • Patent document 5 includes spraying a coating solution or suspension comprising sugar or starch or a mixture of sugar and starch onto a tablet or tablet core to obtain a coated tablet, provided that film formation in the coating solution or suspension Disclosed is a tablet core coating method wherein the material is removed.
  • tablet cores were prepared from mannitol (21.4%), soluble starch (21.4%), silicon dioxide (2.0%), talc (31.8%), titanium dioxide (21.4%). ) And aspartame (2.0%).
  • This sugar-coated film is not intended for orally disintegrating tablets, and it is completely unknown whether a coated tablet that maintains the characteristics of orally disintegrating tablets can be produced.
  • this coated tablet is that the tablet already disintegrates in the patient's mouth when contacted with saliva or another liquid, which can be uncomfortable for the patient, as can occur with uncoated tablets. It is described that the release of the active compound can be controlled and can be interpreted as delaying disintegration in the oral cavity.
  • use of mannitol and starch is essential, and trehalose and erythritol are not described at all regarding sugar.
  • a coating film is formed on an uncoated tablet by a conventional method, it is necessary to repeatedly apply a coating solution to the uncoated tablet and dry it, which causes a problem that it takes time to form the coating film.
  • JP 2010-248106 A JP-A-6-227975 Japanese Patent Laid-Open No. 7-143876 JP 2002-179559 A Special table 2003-514848 gazette
  • the present invention obtains a coated tablet that maintains the characteristics of an orally disintegrating tablet that achieves the contradictory properties of fast disintegration and hardness, and is difficult to crack and has a smooth surface despite the thin coating film.
  • An object of the present invention is to provide an outermost layer coating composition and an outermost layer coating solution that can be applied.
  • Another object of the present invention is to provide a coated tablet prepared using the outermost layer coating composition and the outermost layer coating solution.
  • Another object of the present invention is to provide an industrially excellent method for producing a coated tablet.
  • the present invention provides at least one water-insoluble inorganic compound and / or water selected from the group consisting of a specific saccharide and a water-insoluble inorganic salt having a specific average particle diameter, a silicate compound, aluminum hydroxide, magnesium oxide and zinc oxide.
  • a specific sugar is used as a matrix to favorably incorporate the water-insoluble inorganic compound and / or the water-insoluble fatty acid, a salt thereof or an ester thereof. This is based on the knowledge that a thin and smooth film can be formed to solve the above-mentioned problems.
  • the coating composition when the coating composition was made to contain titanium oxide in order to further improve the appearance of the coated tablet, a problem was found that the color tone of the coating changes due to ultraviolet rays. This problem is particularly problematic in tablet coating.
  • the present invention is based on the knowledge that the coating composition can contain at least one organic compound selected from an organic binder, a water-soluble polymer, and a disintegrant to solve this color change problem. It was made. That is, the first aspect of the present invention is the following coating composition. (1-1) At least one selected from the group consisting of trehalose and / or erythritol and water-insoluble inorganic salts having an average particle size of 0.1 to 50 ⁇ m, silicate compounds, aluminum hydroxide, magnesium oxide and zinc oxide.
  • An outermost layer coating composition for forming a film having a thickness of 100 ⁇ m or less as an outermost layer of a tablet comprising a water-insoluble inorganic compound and / or a water-insoluble fatty acid, a salt thereof or an ester thereof.
  • Trehalose and / or erythritol In the above (1-1), the water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof is in the range of 1: 3 to 3: 1 (mass ratio).
  • the water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof is in the range of 1: 2 to 2: 1 (mass ratio).
  • the coating composition as described. (1-4) The coating composition according to any one of (1-1) to (1-3) above, wherein the water-insoluble inorganic compound is a silicate compound. (1-5) The above (1-), wherein the silicate compound is one or more selected from the group consisting of talc, magnesium aluminate metasilicate, silicon dioxide, kaolin, magnesium silicate, hydrous silicon dioxide, and light anhydrous silicic acid.
  • the water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof has an average particle diameter in the range of 1 to 20 ⁇ m, and any one of (1-1) to (1-7) above Coating composition.
  • the colorant is titanium oxide, iron oxide (black iron oxide), iron sesquioxide (red iron oxide), yellow iron sesquioxide, zinc oxide, water-soluble edible tar dye, water-insoluble lake dye, riboflavin
  • the coating composition according to (1-13) which is at least one water-insoluble inorganic particle or light stabilizer selected from the group consisting of chlorophyll and barium sulfate.
  • the second aspect of the present invention is the following coating solution.
  • (2-3) The coating liquid according to (2-1) or (2-2) above, wherein the alcohol is methanol and / or ethanol.
  • the third aspect of the present invention is the following coated tablet.
  • (3-1) At least one selected from the group consisting of trehalose and / or erythritol and water-insoluble inorganic salts having an average particle diameter of 0.1 to 50 ⁇ m, silicate compounds, aluminum hydroxide, magnesium oxide and zinc oxide.
  • the water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof has an average particle diameter in the range of 1 to 20 ⁇ m, as described in any one of (3-1) to (3-7) above Coated tablets.
  • (3-9) The coated tablet according to (3-8) above, wherein the average particle size of the water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof is in the range of 5 to 10 ⁇ m.
  • a fourth aspect of the present invention is the following method for producing a coated tablet.
  • (4-1) A method for producing a coated tablet, wherein the coating liquid is formed as an outermost layer of the tablet with a thickness of 100 ⁇ m or less.
  • (4-2) The method for producing a coated tablet according to (4-1), wherein the thickness of the outermost layer is 50 ⁇ m or less.
  • (4-3) The method for producing a coated tablet according to (4-1), wherein the thickness of the outermost layer is 20 ⁇ m or less.
  • the fifth aspect of the present invention is the following coating composition that effectively reduces coloring by light, particularly ultraviolet rays.
  • (5-1) Titanium oxide, iron oxide (black iron oxide), iron sesquioxide (red iron oxide), at least one water-insoluble inorganic particle selected from the group consisting of yellow iron sesquioxide and zinc oxide, and an organic bond
  • a composition for coating a tablet which contains at least one organic compound selected from the group consisting of an agent, a water-soluble polymer, and a disintegrant, wherein discoloration due to ultraviolet rays of the water-insoluble inorganic particles is reduced .
  • An outermost layer coating composition for forming an outermost layer of an orally disintegrating tablet comprising at least one organic compound selected from the group consisting of an agent, a water-soluble polymer and a disintegrant.
  • the sixth aspect of the present invention is at least one water selected from the group consisting of titanium oxide, iron oxide (black iron oxide), iron sesquioxide (red iron oxide), yellow iron sesquioxide and zinc oxide.
  • This is a method for reducing discoloration of a composition containing insoluble inorganic particles due to light, particularly ultraviolet rays.
  • (6-1) A composition containing at least one water-insoluble inorganic particle selected from the group consisting of titanium oxide, iron oxide (black iron oxide), iron sesquioxide (red iron oxide), yellow iron sesquioxide and zinc oxide.
  • a film having a thickness of 100 ⁇ m or less can be applied as the outermost layer of the tablet by combining only water-insoluble fatty acids, salts thereof or esters thereof. Therefore, there is an advantage that it is not necessary to use a commonly used organic binder and / or water-soluble polymer. There are few problems of delamination.
  • the storage stability of the active ingredient such as shading and moisture prevention is improved, and contact with active ingredients of persons other than patients is prevented.
  • the effect of can be achieved.
  • the external appearance of the tablet coated with the coating composition of the present invention has few irregularities and good slipperiness, it is excellent in production efficiency and handleability, and excellent in applicability and beauty.
  • a colorant and / or a light stabilizer is added to the coating composition of the present invention, the appearance is further improved, and the storage stability of the active ingredient is improved by the light shielding effect.
  • the coating composition of the present invention has at least one, preferably all of the above preferred properties.
  • the coating composition of the present invention comprises trehalose and / or erythritol and water-insoluble inorganic salts having an average particle size of 0.1 to 50 ⁇ m, preferably 1 to 20 ⁇ m, more preferably 5 to 10 ⁇ m, silicate compounds, aluminum hydroxide , At least one water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof selected from the group consisting of magnesium oxide and zinc oxide is 30% or more, preferably 50% by mass or more of the entire coating composition, More preferably, it is used in an amount of 60% by mass or more, particularly preferably 70% by mass or more.
  • the trehalose and / or erythritol used in the coating composition of the present invention is contained as an essential component.
  • Trehalose is a kind of disaccharide formed by combining 1,1-glycoside with glucose, and is a white powdery crystal at normal temperature and pressure.
  • any of ⁇ , ⁇ -trehalose, ⁇ , ⁇ -trehalose and ⁇ , ⁇ -trehalose may be used, but naturally occurring ⁇ , ⁇ -trehalose is preferably used. Further, a water-containing crystallized product may be used.
  • erythritol is a natural sugar alcohol contained in fruits and the like. Both trehalose and erythritol are readily available from the market.
  • trehalose examples include treha (high-purity water-containing crystal ⁇ , ⁇ -trehalose, Hayashibara Biochemical Laboratories), trehalose ( ⁇ , ⁇ -trehalose, Asahi Kasei Corporation), and the like.
  • An example of erythritol is erythritol (Mitsubishi Corporation Food Tech).
  • Trehalose and erythricol have low hygroscopicity among sugars and can be preferably used in a coating composition for orally disintegrating tablets.
  • the coating composition of the present invention contains trehalose and / or erythritol in an amount of 10% by mass or more, preferably 15% by mass or more, more preferably 20% by mass or more of the entire coating composition. Further, it is preferably 10 to 90% by mass, more preferably 15 to 80% by mass, and particularly preferably 20 to 70% by mass.
  • a silicate compound is preferable.
  • the silicate compound include talc, magnesium aluminate metasilicate, silicon dioxide, kaolin, magnesium silicate, hydrous silicon dioxide, and light anhydrous silicic acid. Talc and magnesium aluminate metasilicate are particularly desirable.
  • the inorganic compound other than the silicate compound include dry aluminum hydroxide gel, magnesium oxide, aluminum hydroxide, and zinc oxide.
  • the water-insoluble inorganic salts include tricalcium phosphate, calcium hydrogen phosphate, magnesium carbonate, and calcium carbonate.
  • water-insoluble fatty acid, salt or ester thereof used in the coating composition of the present invention examples include stearic acid or a salt thereof, sodium stearyl fumarate, sucrose fatty acid ester and the like.
  • the above water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof can be easily obtained from the market.
  • high filler # 7 (Matsumura Sangyo Co., Ltd., average particle size 5 ⁇ m by laser diffraction method)
  • high filler # 12 (Matsumura Sangyo Co., Ltd., average particle size 3 ⁇ m by laser diffraction method)
  • high filler # 17 (Matsumura Sangyo Co., Ltd., average particle size 7.4 ⁇ m by laser diffraction method)
  • UM talc Liuzenac Pharma, average particle size 3.6 ⁇ m by laser diffraction method
  • M talc (Luzenac Pharma, average particle size 4 by laser diffraction method) .7 ⁇ m) and the like.
  • Neusilin type FH1 (Fuji Chemical Industry Co., Ltd., average particle diameter 10.7 ⁇ m by laser diffraction method)
  • Neusilin type FL1 (Fuji Chemical Industry Co., Ltd., average particle diameter 5 by laser diffraction method) 0.4 ⁇ m
  • Neusilin type UFL2 (Fuji Chemical Industry Co., Ltd., average particle diameter 4.3 ⁇ m by laser diffraction method) and the like.
  • sodium stearyl fumarate include probe (JRS Pharma, average particle diameter of 22 ⁇ m by laser diffraction method), probe CG (JRS Pharma, average particle diameter of 35 ⁇ m by laser diffraction method), and the like.
  • water insolubility is defined by the Japanese Pharmacopoeia.
  • the powder When the powder is passed through a No. 100 (150 ⁇ m) sieve, it is placed in a solvent and shaken vigorously every 5 minutes at 20 ⁇ 5 ° C for 30 seconds.
  • the degree of dissolution within 30 minutes means that it is extremely difficult to dissolve (the amount of solvent necessary for dissolving 1 g of solute is 1000 ml or more and less than 10,000 ml) and hardly dissolved (10,000 ml or more).
  • the average particle size of the water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof used in the present invention is 0.1-50 ⁇ m, preferably 1-20 ⁇ m, more preferably 5-10 ⁇ m.
  • the average particle size is desirably 80% or less, preferably 60% or less, more preferably 40% or less, and further preferably 20% or less of the thickness of the outermost layer coating film.
  • the average particle diameter can be easily measured by a laser diffraction method using, for example, a laser diffraction / scattering particle diameter / particle size distribution measuring apparatus (for example, Microtrac MT3100 II (Nikkiso Co., Ltd.)).
  • the present invention at least one selected from the group consisting of trehalose and / or erythritol and water-insoluble inorganic salts having an average particle size of 0.1 to 50 ⁇ m, silicate compounds, aluminum hydroxide, magnesium oxide and zinc oxide.
  • the outermost layer of the orally disintegrating tablet is 100 ⁇ m or less, preferably 50 ⁇ m or less, more preferably 20 ⁇ m or less.
  • the thickness is preferably 1 to 50 ⁇ m, more preferably 1 to 30 ⁇ m, still more preferably 2 to 20 ⁇ m.
  • the thickness is preferably 5 ⁇ m or more, preferably 5 to 100 ⁇ m, more preferably 5 to 50 ⁇ m, still more preferably 10 to 50 ⁇ m, and particularly preferably 10 to 30 ⁇ m.
  • the layer thickness of the outermost layer can be measured by using a method and equipment usually used in the scientific and industrial fields. Although the following methods are illustrated, it is not limited to these methods.
  • the section of the coated tablet cut with a cutter is observed with a digital microscope or a scanning electron microscope, the thickness of the coating layer is measured at a plurality of locations, and the average value of the measured values is taken as the layer thickness. Any two or more measurement locations are preferable, more preferably any three or more locations, and an average value of measurement values at any three locations is usually sufficient.
  • Using a near-infrared / mid-infrared / far-infrared imaging system or a terahertz imaging system measure the layer thickness distribution of the coated tablets non-invasively according to the measurement method of each system, and calculate the average value of those measurements. Layer thickness.
  • MatrixNIR TM system (Spectraldimentions) as a near infrared imaging system, Spotlight 400N (PerkinElmer), Frontier FT IR / NIR as a near infrared / middle infrared / far infrared imaging system / MIR / FIR system (Perkin Elmer) and others include TAS7500 terahertz imaging system (Advantest) and TPI Image 2000 (TeraView) as terahertz imaging systems.
  • TAS7500 terahertz imaging system Advancedest
  • TPI Image 2000 TeleView
  • trehalose and / or erythritol a water-insoluble inorganic compound and / or a water-insoluble fatty acid, a salt thereof or an ester thereof is preferably used in a range of 1: 4 to 4: 1 (mass ratio). More preferably, it is used in the range of 3: 1 (mass ratio), and more preferably in the range of 1: 2 to 2: 1 (mass ratio).
  • the combination of trehalose and / or erythritol and the water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof in the coating composition of the present invention is not particularly limited, but the following combinations may be exemplified. it can.
  • a combination of trehalose and talc (2) Combination of trehalose and magnesium aluminate metasilicate; (3) A combination of trehalose and one or more selected from the group consisting of silicon dioxide, kaolin, magnesium silicate, hydrous silicon dioxide, and light anhydrous silicic acid; (4) A combination of trehalose and one or more selected from the group consisting of dried aluminum hydroxide gel, magnesium oxide, aluminum hydroxide, magnesium carbonate, zinc oxide and calcium carbonate; (5) A combination of trehalose and one or more selected from the group consisting of stearic acid or a salt thereof, sodium stearyl fumarate, sucrose fatty acid ester; (6) A combination of erythritol and talc; (7) Combination of erythritol and magnesium aluminate metasilicate; (8) A combination of erythritol and one or more selected from the group consisting of silicon dioxide, kaolin, magnesium silicate, hydrous silicon dioxide, and light anhydr
  • the following combinations can be exemplified.
  • the coating composition of the present invention can contain various components as long as the effects of the present invention are not affected.
  • examples of such components include water-insoluble inorganic particles other than inorganic compounds such as titanium oxide, iron oxide (black iron oxide), iron sesquioxide (red iron oxide), yellow iron sesquioxide, and zinc oxide. These compounds can be used as a colorant and / or a light stabilizer, and can improve the appearance of the coated tablet or improve the storage stability of the active ingredient due to light shielding.
  • auxiliary inorganic particles have an average particle diameter of 0.1 to 50 ⁇ m, preferably 1 to 20 ⁇ m.
  • the auxiliary inorganic particles are preferably used in an amount of 50% by mass or less, more preferably 1 to 20% by mass.
  • the coating composition of the present invention comprises at least one water-insoluble inorganic particle selected from the group consisting of titanium oxide, iron oxide (black iron oxide), iron sesquioxide (red iron oxide), yellow iron sesquioxide and zinc oxide.
  • the organic compound is preferably used in a proportion of 10 to 1000 parts by weight, more preferably 30 to 1000 parts by weight, still more preferably 50 to 800 parts by weight, particularly preferably 100 parts by weight of the inorganic particles. 60 to 600 parts by mass.
  • organic binders water-soluble polymers and disintegrants
  • water-soluble low-viscosity organic binders such as pullulan, crystalline cellulose, powdered cellulose, hypromellose, dextrin, corn starch, pregelatinized starch, and partially pregelatinized Suspending and swelling organic binders such as starch, water-soluble polymers such as Macrogol 6000, and disintegrants such as crospovidone are preferred.
  • the crystalline cellulose, crospovidone, hypromellose and macrogol 6000 which are representative compounds of organic binders, water-soluble polymers and disintegrants, the effect of suppressing the discoloration of titanium oxide to light blue-white by light These compounds are more preferable.
  • the coating composition of the present invention is preferably prepared from only the above components and does not contain an organic binder and / or a water-soluble polymer, but can also contain additives usually used in the pharmaceutical field.
  • the particle size of the additive of the coating composition of the present invention is preferably about 50 ⁇ m or less, and more preferably about 20 ⁇ m or less.
  • additives used include organic binders and / or water-soluble polymers, excipients, disintegrants, lubricants, surfactants, sweeteners, flavoring agents, flavoring agents / fragrances, and fluidizing agents. , PH adjusting agents, colorants, stabilizers, light stabilizers, moisture-proofing agents, and the like.
  • the coating composition of the present invention is used in the pharmaceutical field as necessary for further improving the appearance of the coated tablet or for improving the storage stability of the active ingredient by shading.
  • An embodiment containing an acceptable colorant and / or a light stabilizer is also preferred.
  • the pharmaceutically acceptable colorant and / or light stabilizer is not particularly limited.
  • the above-described titanium oxide, iron oxide (black iron oxide), iron sesquioxide (red iron oxide), yellow three Examples thereof include water-insoluble inorganic particles other than inorganic compounds such as iron dioxide and zinc oxide, and compounds listed as light stabilizers described later.
  • organic binder and / or water-soluble polymer examples include gum arabic powder, pullulan, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose 2208 (HPMC2208), hydroxypropylmethylcellulose 2906 (HPMC2906), and hydroxypropylmethylcellulose 2910 (HPMC2910).
  • HPC hydroxypropylcellulose
  • HPMC2208 hydroxypropylmethylcellulose 2208
  • HPMC2906 hydroxypropylmethylcellulose 2906
  • HPMC2910 hydroxypropylmethylcellulose 2910
  • PVP polyvinylpyrrolidone
  • PVA Carboxyvinyl polymer
  • PVA polyvinyl alcohol
  • the coating composition of the present invention can be produced without adding an organic binder and / or a water-soluble polymer.
  • an organic binder and / or a water-soluble polymer is added to the coating composition to reduce the color tone of the coating composition containing water-insoluble inorganic particles such as titanium oxide. It is also possible to add a binder and / or a water-soluble polymer. When an organic binder and / or a water-soluble polymer is added, it is desirable that the content does not affect the effects of the present invention.
  • the content that does not affect the effect of the present invention means that the organic binder and / or water-soluble polymer mass is 30% by mass or less, preferably 20% by mass or less, more preferably, the entire coating composition. It is 15 mass% or less, More preferably, it is 10 mass% or less, Most preferably, it is 5% mass or less.
  • organic binders and / or water-soluble polymers those that are preferably used in the coating composition of the present invention are water-soluble organic binders having low viscosity, and examples thereof include pullulan.
  • suspendable and swellable organic binders are more preferable, and examples thereof include crystalline cellulose, powdered cellulose, and dextrin. These materials are less prone to sliminess and decay delay.
  • excipients include precipitated calcium carbonate, calcium monohydrogen phosphate, calcium hydrogen phosphate, sodium hydrogen phosphate, dipotassium phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, sodium dihydrogen phosphate. , Calcium sulfate, calcium lactate, synthetic aluminum silicate, synthetic hydrosite, dry aluminum hydroxide, magnesium carbonate, magnesium oxide, carmellose, carmellose calcium, carmellose sodium, carboxymethyl ethyl cellulose, carboxy starch sodium and the like.
  • disintegrant examples include carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, hydroxypropyl starch and the like.
  • lubricant examples include glyceryl monostearate, glyceryl palmitostearate, sodium stearyl fumarate, sucrose fatty acid ester, carnauba wax, L-leucine, macrogol and the like.
  • surfactant examples include sodium lauryl sulfate, polysorbate 80, hydrogenated oil, polyoxyethylene (105) polyoxypropylene (5) glycol (PEP101), polyoxyethylene (160) polyoxypropylene (30) glycol, and the like. Can be mentioned.
  • sweetening agent examples include aspartame, amateur, fructose, xylitol, glycyrrhizic acid or a salt thereof, saccharin, sucralose, stevia extract, sucrose, D-sorbitol, glucose, maltitol, D-mannitol and the like.
  • flavoring agent examples include ascorbic acid or a salt thereof, sodium chloride, magnesium chloride, citric acid or a salt thereof, glycine, glucono- ⁇ -lactone, L-glutamic acid or a salt thereof, succinic acid or a salt thereof, ⁇ -cyclodextrin , Tartaric acid or a salt thereof, skim milk powder, sodium bicarbonate, lactic acid or a salt thereof, fumaric acid or a salt thereof, menthol, DL-malic acid or a salt thereof, and the like.
  • Examples of the fluidizing agent include calcium carbonate, calcium phosphate, gypsum, magnesium carbonate, synthetic aluminum silicate, magnesium alumina hydroxide, corn starch, calcium hydrogen phosphate granule, and glyceryl monostearate.
  • Examples of the pH adjuster include citrate, phosphate, carbonate, tartrate, fumarate, acetate, amino acid salt and the like.
  • Examples of the stabilizer include sodium edetate, tocopherol, cyclodextrin and the like.
  • Examples of light stabilizers include water-soluble food tar dyes (food yellow No. 5, food blue No.
  • water-insoluble lake dyes water-soluble tar dye salts
  • riboflavin chlorophyll
  • talc zinc oxide
  • sulfuric acid examples include barium.
  • An embodiment in which the coating composition of the present invention contains a light stabilizer is also preferable.
  • the desiccant include ethyl cellulose, vinyl acetate resin, purified shellac, seraphate, and white shellac.
  • the coating composition of the present invention is preferably used as an outermost layer coating solution obtained by dissolving and dispersing the above components in water and / or alcohol.
  • trehalose and / or erythritol is preferably prepared so as to contain at a concentration of 0.5 to 20% by mass, preferably 1 to 10% by mass, more preferably 1 to 5% by mass.
  • a lower alcohol such as methanol, ethanol, isopropanol, etc. can be used as the alcohol, and ethanol, particularly anhydrous ethanol is preferred.
  • ethanol means that containing 95% by volume or more of ethanol
  • absolute ethanol means that containing 99.5% or more by volume of ethanol.
  • Alcohol ranges from 1: 1 to 20: 1, preferably from 2: 1 to 10: 1, more preferably from 3: 1 to 5: 1.
  • an interfacial tension adjusting agent that lowers the interfacial tension of the coating liquid for example, a nonionic surfactant, can also be added.
  • a nonionic surfactant for example, a nonionic surfactant
  • the coating solution is applied to an orally disintegrating tablet (plain tablet) by an ordinary method, for example, a spray coating method, with a thickness of 100 ⁇ m or less as an outermost layer, preferably 2 to 50 ⁇ m, more preferably 5 to 20 ⁇ m It is preferable to produce a coated tablet by forming such that The preferred coating film thickness is as described above.
  • a spray coating method with a thickness of 100 ⁇ m or less as an outermost layer, preferably 2 to 50 ⁇ m, more preferably 5 to 20 ⁇ m
  • the preferred coating film thickness is as described above.
  • Commercially available pan coating devices, fluidized bed coating devices, full-time rotary drum coating devices, and the like can be used, and full-year rotary drum coating devices are particularly suitable.
  • the coating liquid is preferably applied to the orally disintegrating tablet (uncoated tablet) as a single layer, but the orally disintegrating tablet (uncoated tablet) and a layer (outermost layer) formed of the coating liquid; In between, one or more additional intermediate layers can be provided.
  • the total thickness of the coating layers provided for the orally disintegrating tablets (plain tablets) is preferably 100 ⁇ m or less, more preferably 50 ⁇ m or less.
  • the intermediate layer that can be provided in the present invention is not particularly limited as long as it does not impair the effects of the present invention, but preferably contains trehalose and / or erythritol, and further contains the various components described above. Also good. Particularly preferred can be set according to the embodiment of the outermost layer coating solution of the present invention.
  • the intermediate layer coating is preferably used as an intermediate layer coating solution obtained by dissolving and dispersing the intermediate layer coating component in water and / or alcohol.
  • preferable mass% of trehalose and / or erythritol, alcohol type, water: alcohol ratio, and interfacial tension adjuster addition can be set according to the outermost layer coating solution.
  • the intermediate layer coating solution is formed on an orally disintegrating tablet (plain tablet) by a conventional method such as spray coating so that the thickness is 50 ⁇ m or less, preferably 1 to 30 ⁇ m, more preferably 2 to 20 ⁇ m. It is preferable.
  • the coating composition may contain other than inorganic compounds such as titanium oxide. It is possible to contain water-insoluble inorganic particles. In this case, it is preferable to use an outermost layer coating composition that effectively reduces changes in the color tone of the coated tablet due to light, particularly ultraviolet rays.
  • the at least one organic compound selected from the group consisting of an organic binder, a water-soluble polymer, and a disintegrant those described above are preferable.
  • the preferable ratio of the said inorganic particle and the said organic compound is as above-mentioned.
  • the inorganic particles are preferably contained in an amount of 1 to 67% by mass, more preferably 1 to 50% by mass, further preferably 5 to 45% by mass, and particularly preferably 10 to 40% by mass based on the outermost layer coating composition. % Content is preferable.
  • the outermost layer coating composition may further contain other polysaccharides in addition to trehalose and erythritol.
  • the content of such a polysaccharide is preferably 0.1 to 50% by mass based on the outermost layer coating composition.
  • the salt or ester thereof is preferably contained in an amount of 1 to 70% by mass, more preferably 5 to 60% by mass, and further preferably 10 to 50% by mass, based on the outermost layer coating composition.
  • the water-insoluble inorganic compound and / or water-insoluble fatty acid, salt or ester thereof are as described above.
  • the orally disintegrating tablet (plain tablet) to which the coating composition of the present invention is applied is not particularly limited as long as it is within the range normally used as an orally disintegrating tablet (plain tablet) in the industry.
  • it is an orally disintegrating tablet as defined in the 16th revised Japanese Pharmacopoeia General Rules for Preparations 1.1.1, and it is rapidly dissolved or disintegrated in the oral cavity with oral saliva or a small amount of water.
  • Possible orally disintegrating tablets can be used.
  • the disintegration time measured by the method of Test Example 1 described later is 60 seconds or less, preferably 40 seconds or less, more preferably 20 seconds or less.
  • an intraoral-dissolving tablet produced by tableting a mixture containing a medicinal ingredient described in JP-A-5-271054, a saccharide, and water having a wetness to the particle surface of the saccharide, WO 95/20380
  • An oral dissolution-type compression-molded product comprising a low-moldability saccharide and a high-moldability saccharide described in the publication, and having rapid disintegration and solubility in the oral cavity, and a drug described in WO99 / 47124
  • the low melting sugar Orally disintegrating tablets produced by forming a cross-link with the drug and / or the diluent particles with a melt-solidified product of the saccharide having a low melting point JP-A-2001-328948
  • These orally disintegrating tablets (plain tablets) can be easily produced by the method described in the above-mentioned patent document.
  • a foaming disintegrant described in JP-A-5-50056 can also be contained.
  • as orally disintegrating tablets in addition to the active ingredient drug, contain one or more from the group consisting of mannitol, xylitol, crystalline cellulose, crospovidone, magnesium aluminate metasilicate, and the like. Those are preferred.
  • the shape and size of the coated tablet formed with the coating composition of the present invention is not particularly limited, but from the viewpoint of ease of taking, a round tablet or an elliptical tablet having a diameter of about 5 to 15 mm and a thickness of about 2 to 5 mm.
  • it is a flower-shaped tablet or the like.
  • the active ingredient contained in the coated tablet of the present invention is not particularly limited, the active ingredient commercially available as an orally disintegrating tablet (droxidopa, cilostazol, selegiline hydrochloride, acarbose, voglibose, glimepiride, pioglidazone, amlodipine, midodrine hydrochloride , Ebastine, olopatadine hydrochloride, cetirizine hydrochloride, fexofenadine hydrochloride, bepotastine besylate, imidafenacin, solifenacin succinate, tamsulosin hydrochloride, naphthopidyl, famotidine, lansoprazole, irsogladine maleate, precipitated calcium carbonate , Polaprezinc, rebamipide, tartyrelin hydrate, ramosetron hydrochloride, risperidone, brot
  • Uncoated tablet A The following ingredients were weighed, mixed and tableted to obtain about 9 kg (about 90,000 tablets) of uncoated tablet A having a diameter of 6.5 mm and a thickness of 3.2 mm of about 100 mg / tablet.
  • Uncoated tablet C (dienogest tablet) 0.100 kg of dienogest is added to the ingredients of uncoated tablet B, manufactured in the same manner as uncoated tablet B, and approximately 9 mg (approximately 90,000 tablets) of uncoated tablet C with a diameter of 6.5 mm and a thickness of 3.2 mm of approximately 100 mg / tablet Obtained.
  • Uncoated tablet D The following ingredients were weighed, mixed and tableted to obtain about 9 kg (about 90,000 tablets) of uncoated tablet D having a diameter of 6.5 mm and a thickness of 3.2 mm of about 100 mg / tablet.
  • Trehalose product name: Trehalose G: Hayashibara Biochemical Laboratories
  • 4.5 g was weighed and added to 191.0 g of purified water while stirring with a propeller stirrer to dissolve.
  • talc high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo
  • This coating solution was spray-coated on the uncoated tablets A using a coating apparatus (Dria Coater 200: Powrec) under the following conditions to obtain coated tablets.
  • 200 g of uncoated tablet A (about 2000 tablets) was coated by one coating.
  • Spray speed 4.91 mL / min
  • Spray pressure 0.12 MPa Drum rotation speed: 10rpm
  • Trehalose product name: Trehalose G: Hayashibara Biochemical Laboratories 9.0 g was weighed and added to 186.5 g of purified water with stirring with a propeller stirrer, and dissolved. Next, 4.5 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 4.5 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed, respectively, and the above trehalose In addition to the solution, it was uniformly dispersed to form a coating solution [trehalose 4.4 mass%, talc 2.2 mass%, and titanium oxide 2.2 mass%].
  • This coating solution was spray-coated on the uncoated tablets A using a coating apparatus (Dria Coater 200: Paulek) under the same conditions as in Example 1 to obtain coated tablets. 200 g of uncoated tablet A (about 2000 tablets) was coated by one coating.
  • Example 3 Erythritol (product name erythritol: Mitsubishi Corporation Foodtech) 6.0 g was weighed and added to 191.0 g of purified water while stirring with a propeller stirrer to dissolve. Next, 6.0 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 3.0 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed, and the above erythritol was measured. In addition to the solution, it was uniformly dispersed to obtain a coating liquid [erythritol 2.9% by mass, talc 2.9% by mass and titanium oxide 1.5% by mass].
  • a specified amount of this coating solution was spray-coated on the uncoated tablets B under the same conditions as in Example 1 using a coating apparatus (Dria Coater 200: Paulek) to obtain coated tablets. 200 g of uncoated tablet B (about 2000 tablets) was coated by one coating.
  • Example 4 A propeller stirrer is prepared by weighing 10.0 g of trehalose (product name: trehalose G: Hayashibara Biochemical Laboratories) and mixing 125.0 g of purified water and 40.0 g of 99.5% ethanol (reagent special grade: Wako Pure Chemical Industries). The solution was added with stirring at a temperature and dissolved. Next, 20.0 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 5.0 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed, and the above trehalose was measured.
  • trehalose product name: trehalose G: Hayashibara Biochemical Laboratories
  • talc high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo
  • titanium oxide average particle size 0.6 ⁇ m, product name NA65: Toho Titanium
  • a coating solution [trehalose 5.0 mass%, talc 10.0 mass% and titanium oxide 2.5 mass%].
  • a specified amount of this coating solution was spray-coated on the uncoated tablets B under the same conditions as in Example 1 using a coating apparatus (Dria Coater 200: Paulek) to obtain coated tablets. 200 g of uncoated tablet B (about 2000 tablets) was coated by one coating.
  • Trehalose product name: Trehalose G: Hayashibara Biochemical Laboratories
  • 4.5 g was weighed and added to 191.0 g of purified water while stirring with a propeller stirrer to dissolve.
  • 4.5 g of crospovidone (Kollidon CL-SF, average particle size 17 ⁇ m: BASF) was weighed, added to the trehalose solution, and uniformly dispersed to form a coating solution [2.3% by mass of trehalose, crospovidone 2. 3% by mass].
  • This coating solution was spray-coated on the uncoated tablets A using a coating apparatus (Dria Coater 200: Paulek) under the same conditions as in Example 1 to obtain coated tablets. 200 g of uncoated tablet A (about 2000 tablets) was coated by one coating.
  • Trehalose product name: Trehalose G: Hayashibara Biochemical Laboratories
  • 4.5 g was weighed and added to 191.0 g of purified water while stirring with a propeller stirrer to dissolve.
  • 4.5 g of titanium oxide average particle size 0.6 ⁇ m, product name NA65: Toho Titanium
  • This coating solution was spray-coated on the uncoated tablets A using a coating apparatus (Dria Coater 200: Paulek) under the same conditions as in Example 1 to obtain coated tablets.
  • 200 g of uncoated tablet A (about 2000 tablets) was coated by one coating.
  • Test Example 1 ⁇ Disintegration time> The uncoated tablet or coated tablet was measured under the following conditions using an orally disintegrating tablet tester (ODT-101: Toyama Sangyo). The average value of the measured values of 3 tablets was taken as the disintegration time.
  • Test Example 2 ⁇ Hardness> The plain tablet or the coated tablet was measured by a conventional method using a tablet hardness meter (8M: Dr. Schleuniger Pharmatron AG). The average value of the measured values of 10 tablets was defined as hardness (Newton: N).
  • Test Example 3 ⁇ Slip angle> A short side of a rectangular stainless steel plate measuring 17 cm ⁇ 28.5 cm was placed on a horizontal desk, and the short side facing each other was lifted with a jack to be inclined. Three plain tablets or coated tablets were put on the highest place on the stainless steel plate, and the angle between the stainless steel plate and the desk surface when all three tablets slipped was calculated, and this was taken as the sliding angle.
  • Test Example 4 ⁇ Drop test> Ten uncoated tablets or coated tablets were dropped from a height of 1 m onto a stainless steel plate, and the presence or absence of cracks was confirmed visually and using a digital microscope (VHX-600: Keyence). The degree of change is indicated by the following symbols. A: No change, B: Very small crushing at a level that cannot be visually confirmed, B: Crushing and chipping that can be visually confirmed, X: Cracking Test Example 5 ⁇ Appearance> Appearance was confirmed using visual and fingertip palpation. The degree of appearance is indicated by the following symbols.
  • Example 6 ⁇ Layer thickness> The cross section of the coated tablet cut with a cutter was observed with an electron microscope (S-3400N), and the thickness of the coating layer was measured. The average value of the measured values at three locations was defined as the layer thickness. Tables 1 and 2 show the evaluation results.
  • Example 1 the coating was applied without impairing the disintegration time and hardness of the uncoated tablet.
  • the appearance was smooth, and in particular, Example 4 was glossy and excellent results were obtained.
  • the sliding angle was smaller than that of the uncoated tablet, and it slipped at a gentle angle.
  • the appearance of Comparative Example 1 was somewhat rough and uneven.
  • the sliding angles of Comparative Examples 1 and 2 were larger by 2 ° or more than the uncoated tablets.
  • the colorant and / or the light stabilizer, titanium oxide was not contained and the appearance was slightly inferior, but there was no problem with the smoothness of the coating surface.
  • Example 5 180 g of trehalose (product name: trehalose G: Hayashibara Biochemical Laboratories) was weighed and added to 3780 g of purified water while stirring with a propeller stirrer to dissolve. Next, 180 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 60 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed and added to the trehalose solution. It was uniformly dispersed to form a coating solution [trehalose 4.3 mass%, talc 4.3 mass% and titanium oxide 1.4 mass%].
  • This coating solution was spray-coated on the uncoated tablets B using a coating apparatus (Paurec coater PRC-7: Paulek) under the following conditions to obtain coated tablets. 3000 g of uncoated tablets B (about 30,000 tablets) were coated in one coating. Supply temperature: 65 ° C Air volume: 3.5m 3 / min Spray speed: 30 g / min Drum rotation speed: 12rpm
  • Example 6 120 g of trehalose (product name: trehalose G: Hayashibara Biochemical Laboratories) was weighed and added to 2600 g of purified water while stirring with a propeller stirrer to dissolve. Next, 120 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 60 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed and added to the trehalose solution. The coating liquid was uniformly dispersed [trehalose 4.1% by mass, talc 4.1% by mass and titanium oxide 2.1% by mass].
  • This coating solution was spray-coated on the uncoated tablets B using a coating apparatus (Paurec coater PRC-7: Paulek) under the same conditions as in Example 5 to obtain coated tablets. 3000 g of uncoated tablets B (about 30,000 tablets) were coated in one coating.
  • Example 7 60 g of trehalose (product name: trehalose G: Hayashibara Biochemical Laboratories) was weighed and added to 4020 g of purified water while stirring with a propeller stirrer and dissolved. Next, 60 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 60 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed and added to the trehalose solution. It was uniformly dispersed to give a coating solution [trehalose 1.4% by mass, talc 1.4% by mass and titanium oxide 1.4% by mass].
  • This coating solution was spray-coated on the uncoated tablets B using a coating apparatus (Paurec coater PRC-7: Paulek) under the same conditions as in Example 5 to obtain coated tablets. 3000 g of uncoated tablets B (about 30,000 tablets) were coated in one coating.
  • Example 8 90 g of trehalose (product name: trehalose G: Hayashibara Biochemical Laboratories) was weighed and added to 6030 g of purified water while stirring with a propeller stirrer to dissolve. Next, 90 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 90 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed and added to the trehalose solution. It was uniformly dispersed to give a coating solution [trehalose 1.4% by mass, talc 1.4% by mass and titanium oxide 1.4% by mass].
  • This coating solution was spray-coated on the uncoated tablets C using a coating apparatus (Paurec coater PRC-7: Paulek) under the same conditions as in Example 5 to obtain coated tablets. 3000 g of uncoated tablets C (about 30,000 tablets) were coated in one coating. Table 3 summarizes the performance evaluation results of the coated tablets of Examples 5 to 8.
  • Example 5 coating was performed on a scale of 30,000 tablets. As a result, as with the 2000 tablet scale, the coating could be applied without harming the disintegration time and hardness of the uncoated tablet, the sliding angle was smaller than that of the uncoated tablet, and the glossiness increased in appearance.
  • uncoated tablet C containing 1% of active ingredient (dienogest) was used, but the same results were obtained as when uncoated tablet B containing no active ingredient was used.
  • Example 9 Trehalose (product name: Trehalose G: Hayashibara Biochemical Laboratories) 3.0 g was weighed and added to 194.0 g of purified water with stirring with a propeller stirrer, and dissolved. Next, 3.0 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) was weighed, added to the above aqueous solution, and uniformly dispersed to obtain a coating solution for the first layer [trehalose 1.5% by mass And 1.5% by mass of titanium oxide]. The coating solution for the first layer was spray coated on the uncoated tablet B using a coating apparatus (Dria Coater 200: Powrec) under the same conditions as in Example 1 to obtain a first layer coated tablet.
  • a coating apparatus Dria Coater 200: Powrec
  • trehalose was weighed and dissolved in 191.0 g of purified water while stirring with a propeller stirrer.
  • talc high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo
  • the coating solution for the second layer was spray-coated on the first layer-coated tablet using a coating apparatus (Dria Coater 200: Powrec) under the same conditions as in Example 1 to obtain a two-layer coated tablet.
  • 200 g of uncoated tablet B (about 2000 tablets) was coated with the coating of the first layer and the second layer.
  • Example 10 Trehalose (product name: Trehalose G: Hayashibara Biochemical Laboratories) 4.5 g and Macrogol 6000 (product name: Macrogol 6000: Sanyo Kasei) 0.9 g were weighed and stirred in 190.4 g of purified water with a propeller stirrer. Add and dissolve. Next, 1.2 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 3.0 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed, respectively, and the above aqueous solution.
  • talc high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo
  • titanium oxide average particle size 0.6 ⁇ m, product name NA65: Toho Titanium
  • a coating solution for the first layer [trehalose 2.3 mass%, macrogol 6000 0.5% talc 0.6 mass%, and titanium oxide 1.5 mass%].
  • the coating solution for the first layer was spray-coated on the uncoated tablet A using a coating apparatus (Dria Coater 200: Powrec) under the same conditions as in Example 1 to obtain a first layer coated tablet.
  • a coating apparatus Dria Coater 200: Powrec
  • magnesium aluminate metasilicate product name Neusilin UFL2, average particle size 4.3 ⁇ m: Fuji Chemical Industry
  • the coating solution for the second layer was spray-coated on the first layer-coated tablet using a coating apparatus (Dria Coater 200: Powrec) under the same conditions as in Example 1 to obtain a two-layer coated tablet.
  • 200 g of uncoated tablet A (about 2000 tablets) was coated with the coating of the first layer and the second layer.
  • the coating solution for the first layer was spray-coated on the uncoated tablet A using a coating apparatus (Dria Coater 200: Powrec) under the same conditions as in Example 1 to obtain a first layer coated tablet.
  • a coating apparatus Dria Coater 200: Powrec
  • 2.5 g of trehalose and 60002.5 g of macrogol were weighed, added to 95.0 g of purified water while stirring with a propeller stirrer, and dissolved to obtain a coating solution for the second layer [2.5% by mass of trehalose and Macrogol 6000 2.5% by mass].
  • the coating solution for the second layer was spray-coated on the first layer-coated tablet using a coating apparatus (Dria Coater 200: Powrec) under the same conditions as in Example 1 to obtain a two-layer coated tablet. 200 g of uncoated tablet A (about 2000 tablets) was coated with the coating of the first layer and the second layer. Table 4 summarizes the performance evaluation results of the coated tablets of Examples 9 and
  • the second layer (outermost layer) contained talc and magnesium aluminate metasilicate, and good results were obtained in all of the decay time, hardness, appearance, and sliding angle.
  • the first layer contains trehalose and talc, which are good results in Example 1, but the second layer does not contain talc, so the surface has unevenness in appearance.
  • the sliding angle was slightly larger than the uncoated tablet.
  • Example 11 A propeller stirrer is added to a solution obtained by weighing 40.0 g of trehalose (product name: trehalose G: Hayashibara Biochemical Laboratories) and mixing 97.5 g of purified water and 32.5 g of 99.5% ethanol (reagent special grade: Wako Pure Chemical Industries). The solution was added with stirring at a temperature and dissolved. Next, 20.0 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 10.0 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed, and the above trehalose was measured.
  • trehalose product name: trehalose G: Hayashibara Biochemical Laboratories
  • a coating solution [trehalose 20.0% by mass, talc 10.0% by mass and titanium oxide 5.0% by mass].
  • a specified amount of this coating solution was spray-coated on the uncoated tablets B under the same conditions as in Example 1 using a coating apparatus (Dria Coater 200: Paulek) to obtain coated tablets. 200 g of uncoated tablet B (about 2000 tablets) was coated by one coating.
  • Comparative Example 4 Coating was performed according to the method of Example 11 except that the amount of spray solution of Example 11 was about 2.4 times.
  • Comparative Example 5 Coating was performed according to the method of Example 11 except that the amount of spray solution of Example 11 was about 3.8 times. Table 5 summarizes the performance evaluation results of the coated tablets of Example 11 and Comparative Examples 4 and 5.
  • Example 11 was excellent in all of disintegration time, hardness, sliding angle, drop test, and appearance. On the other hand, in Comparative Examples 4 and 5 having a coating layer thicker than Example 11, the disintegration time was delayed as the layer thickness increased, and surface irregularities tended to be conspicuous in appearance.
  • Hypromellose product name TC-5R: Shin-Etsu Chemical
  • Macrogol 6000 product name Macrogol 6000: Sanyo Kasei
  • Comparative Example 6 is an example of film coating, but the disintegration time tended to be delayed compared to Example 4 shown above. This is thought to be due to the fact that hypromellose, which is a water-soluble polymer, is blended at a constant level to form a viscous (slimy) layer with a small amount of water, preventing water penetration into the tablet. Further, the sliding angle was 1 ° or more larger than that of the uncoated tablet, and deterioration of the sliding property was recognized.
  • Example 12 81 g of trehalose (product name: trehalose G: Hayashibara Biochemical Laboratories) was weighed and added to 5922 g of purified water while stirring with a propeller stirrer to dissolve. Next, 81 g of crystalline cellulose (Theorus PH-F20JP: Asahi Kasei Chemicals), 90 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo), titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) ) 90 g and 36 g of crospovidone (Kollidon CL-M, average particle size 5.4 ⁇ m: BASF) were weighed, added to the above aqueous solution, and uniformly dispersed to form a coating solution [trehalose 1.3 mass%, crystalline cellulose 1.
  • Example 12 the coating was applied without impairing the disintegration time and hardness of the uncoated tablet.
  • Crystalline cellulose tends to cause roughness on the coating surface when the dose is increased, and crospovidone also tends to cause unevenness on the coating surface when the dose is increased.
  • the appearance was smooth in all of Examples 12 to 14, and glossy, and excellent results were obtained.
  • Example 12 in which 21.4% of the crystalline cellulose as the organic binder was added, the appearance was good and no decay delay was observed, so at least about 21% of the organic binder was added. However, it was considered that appearance and disintegration were not impaired.
  • Example 1 where the coating layer thickness was 17.3 ⁇ m, and Example 9 where the coating layer thickness was 14.4 ⁇ m, etc., the characteristics of the tablets were good, so that the layer thickness was 10 ⁇ m or more. It was thought that the effect of the present invention could be exhibited.
  • Example 15 Trehalose (product name: Trehalose G: Hayashibara Biochemical Laboratories) 4.2 g was weighed and added to 191.6 g of purified water with stirring with a propeller stirrer and dissolved. Next, 4.2 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) was weighed and added to the above trehalose solution and uniformly dispersed to form a coating solution [trehalose 2.1 mass%, talc 2 .1% by mass]. A specified amount of this coating solution was spray-coated on the uncoated tablets B using a coating apparatus (Dria Coater 200: Powrec) under the following conditions to obtain coated tablets.
  • a coating apparatus Dria Coater 200: Powrec
  • Example 16 Trehalose (product name: Trehalose G: Hayashibara Biochemical Laboratories) 4.2 g was weighed and added to 187.4 g of purified water while stirring with a propeller stirrer and dissolved. Next, 4.2 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo) and 4.2 g of titanium oxide (average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed, respectively, and the above trehalose was measured. In addition to the solution, it was uniformly dispersed to obtain a coating solution [trehalose 2.1 mass%, talc 2.1 mass% and titanium oxide 2.1 mass%].
  • a specified amount of this coating solution was spray coated on the uncoated tablet B using the coating apparatus (Dria Coater 200: Paulek) under the same conditions as in Example 14 to obtain coated tablets. 200 g of uncoated tablet B (about 2000 tablets) was coated by one coating.
  • Example 17 The trehalose of Example 15 was replaced with 4.2 g of erythritol (product name: erythritol fine powder: Mitsubishi Food Chemical), and uncoated tablet B was coated in the same manner.
  • Test Example 7 ⁇ Photostability Test> The coated tablets obtained in Examples 15 to 17 and Example 12 were measured under the following conditions using an environmental tester No. 20 (light stability tester: LT-120D3CJ: Nagano Scientific Machinery Co., Ltd.). went. The coated tablets were arranged so as not to overlap in a glass petri dish and stored in an environmental tester.
  • the tablet with the coating containing trehalose and talc (Example 15) was white at the start of the test, and the color of the tablet remained white at the start of the test even with the light irradiation of 1.2 million Lux ⁇ h. It was.
  • the color of the tablet is the same even when irradiated with 1.2 million Lux ⁇ h.
  • the white color remained unchanged. Only the coating layer was discolored, and the uncoated tablet portion was not discolored. This time, it has been found that crystalline cellulose and / or crospovidone has the effect of suppressing the discoloration of titanium oxide to light blue-white by light.
  • Example 18 Trehalose (product name: Trehalose G: Hayashibara Biochemical Laboratories) 4.5 g and pullulan (product name: pullulan: Hayashibara Biochemistry Laboratories) 0.9 g were weighed and stirred in 190.4 g of purified water with a propeller stirrer. Add and dissolve. Next, 1.2 g of talc (high filler # 17, average particle size 7.4 ⁇ m: Matsumura Sangyo), 3.0 g of titanium oxide average particle size 0.6 ⁇ m, product name NA65: Toho Titanium) were weighed, respectively, into the above aqueous solution.
  • a coating liquid for the first layer [trehalose 2.3 mass%, pullulan 0.5 mass%, talc 0.6 mass%, and titanium oxide 1.5 mass%].
  • the coating solution for the first layer was spray coated on the uncoated tablet A using a coating apparatus (Dria Coater 200: Powrec) under the same conditions as in Example 1 to obtain a first layer coated tablet.
  • a coating apparatus Dria Coater 200: Powrec
  • Example 18 The test results of Example 18 are summarized in Table 9.
  • Example 18 using pullulan as the organic binder and / or water-soluble polymer is excellent in all of the disintegration time, hardness, sliding angle, drop test, and appearance.

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une composition d'enrobage de couche externe destinée à former, en tant que couche externe d'un comprimé à dispersion orale, un film épais ne dépassant pas 100 micromètres - ladite composition étant caractérisée en ce qu'elle contient au moins un type de composé inorganique hydro-insoluble et/ou d'acide gras hydro-insoluble ‑, et son sel ou son ester, sélectionné dans le groupe comprenant du tréhalose et/ou de l'érythritol, des sels inorganiques hydro-insoluble présentant un diamètre de grain moyen compris entre 0,1 et 50 micromètres, des composés d'acide silicique, de l'hydroxyde d'aluminium, de l'oxyde de magnésium, et de l'oxyde de zinc. Cette composition d'enrobage de couche externe conserve les caractéristiques d'un comprimé à dispersion orale combinant les propriétés contraires de dispersion rapide et de dureté, et permet d'obtenir un comprimé enrobé présentant une surface lisse difficile à fissurer, même lorsque le film d'enrobage est mince.
PCT/JP2012/061265 2011-04-28 2012-04-26 Composition d'enrobage présentant une dispersabilité orale supérieure WO2012147873A1 (fr)

Priority Applications (3)

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JP2013512441A JP5690925B2 (ja) 2011-04-28 2012-04-26 口腔内崩壊性に優れたコーティング組成物
PCT/JP2012/077576 WO2013161103A1 (fr) 2012-04-26 2012-10-25 Composition comportant de l'oxyde de titane empêché de changer de couleur
JP2014512292A JP5690972B2 (ja) 2012-04-26 2012-10-25 酸化チタンの変色が抑制された組成物

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JP2011-101285 2011-04-28
JP2011101285 2011-04-28

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WO2014157264A1 (fr) * 2013-03-27 2014-10-02 Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 Comprimé à désintégration orale revêtu d'un film
JP6002870B1 (ja) * 2015-10-16 2016-10-05 持田製薬株式会社 低用量薬物を含有する口腔内崩壊錠
KR20160137507A (ko) 2014-03-31 2016-11-30 도레이 카부시키가이샤 고형 제제용의 코팅제 및 이것으로 형성된 피막 및 피복 고형 제제
JP2018024632A (ja) * 2016-08-02 2018-02-15 エルメッド エーザイ株式会社 口腔内崩壊性被覆錠剤及び口腔内崩壊性被覆錠剤の被覆層用組成物
JP2020147508A (ja) * 2019-03-12 2020-09-17 東和薬品株式会社 勃起不全治療用医薬組成物

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JP6995472B2 (ja) 2016-10-31 2022-01-14 ロレアル 自然な皮膚明色化効果のための組成物

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JP2011063627A (ja) * 2010-08-31 2011-03-31 Kyowa Hakko Kirin Co Ltd 苦味を呈する薬物を含有する顆粒および口腔内崩壊錠

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WO2000054752A1 (fr) * 1999-03-15 2000-09-21 Kaken Pharmaceutical Co., Ltd. Comprimes a delitement rapide et procede de fabrication
JP2009532468A (ja) * 2006-04-04 2009-09-10 マクニール−ピーピーシー・インコーポレイテッド 皮膜でコーティングされた固体状の剤形
WO2008136380A1 (fr) * 2007-04-26 2008-11-13 Eisai R & D Management Co., Ltd. Procédé de production de comprimés
JP2010538664A (ja) * 2007-09-21 2010-12-16 カーギル インコーポレイテッド エリスリトールベースのハードコーティング
JP2011063627A (ja) * 2010-08-31 2011-03-31 Kyowa Hakko Kirin Co Ltd 苦味を呈する薬物を含有する顆粒および口腔内崩壊錠

Cited By (10)

* Cited by examiner, † Cited by third party
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WO2014157264A1 (fr) * 2013-03-27 2014-10-02 Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 Comprimé à désintégration orale revêtu d'un film
JPWO2014157264A1 (ja) * 2013-03-27 2017-02-16 Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 口腔内崩壊性フィルムコーティング錠
KR20160137507A (ko) 2014-03-31 2016-11-30 도레이 카부시키가이샤 고형 제제용의 코팅제 및 이것으로 형성된 피막 및 피복 고형 제제
EP3127555A4 (fr) * 2014-03-31 2017-11-22 Toray Industries, Inc. Préparation solide pour agent d'enrobage, et film et préparation solide enrobée formés à partir de celui-ci
US10022331B2 (en) 2014-03-31 2018-07-17 Toray Industries, Inc. Coating agent for solid preparation, and film and coated solid preparation formed therewith
JP6002870B1 (ja) * 2015-10-16 2016-10-05 持田製薬株式会社 低用量薬物を含有する口腔内崩壊錠
WO2017064815A1 (fr) * 2015-10-16 2017-04-20 持田製薬株式会社 Comprimé à désintégration buccale contenant un médicament à faible dose
JP2018024632A (ja) * 2016-08-02 2018-02-15 エルメッド エーザイ株式会社 口腔内崩壊性被覆錠剤及び口腔内崩壊性被覆錠剤の被覆層用組成物
JP2020147508A (ja) * 2019-03-12 2020-09-17 東和薬品株式会社 勃起不全治療用医薬組成物
JP7391521B2 (ja) 2019-03-12 2023-12-05 東和薬品株式会社 勃起不全治療用医薬組成物

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JPWO2012147873A1 (ja) 2014-07-28
JP2015083615A (ja) 2015-04-30
JP5690925B2 (ja) 2015-03-25

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