WO2008013084A1 - Préparation enrobée de sucre et son procédé de fabrication - Google Patents

Préparation enrobée de sucre et son procédé de fabrication Download PDF

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Publication number
WO2008013084A1
WO2008013084A1 PCT/JP2007/064152 JP2007064152W WO2008013084A1 WO 2008013084 A1 WO2008013084 A1 WO 2008013084A1 JP 2007064152 W JP2007064152 W JP 2007064152W WO 2008013084 A1 WO2008013084 A1 WO 2008013084A1
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WO
WIPO (PCT)
Prior art keywords
sugar
coating
coating liquid
coated
preparation
Prior art date
Application number
PCT/JP2007/064152
Other languages
English (en)
Japanese (ja)
Inventor
Tatsuharu Shimokawa
Hiroyuki Kawashima
Original Assignee
Kowa Company, Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kowa Company, Ltd. filed Critical Kowa Company, Ltd.
Priority to JP2008526734A priority Critical patent/JPWO2008013084A1/ja
Priority to CN2007800281535A priority patent/CN101495101B/zh
Publication of WO2008013084A1 publication Critical patent/WO2008013084A1/fr
Priority to HK09110763.5A priority patent/HK1132664A1/xx

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Classifications

    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the present invention relates to a sugar-coated preparation and a method for producing the same.
  • the sugar-coated preparation has a function of preventing the permeation of oxygen, water, and odorous components from the sugar-coated layer. It is a dosage form suitable for conversion.
  • processed garlic has the effects of recovering fatigue and nourishing tones, enhancing gastric contractile force, promoting metabolism, promoting blood flow, protecting liver, etc. Many of them are made into sugar-coated products.
  • Methylmethioninesulfonium chloride (hereinafter also referred to as “MMSC”) is an improvement in subjective symptoms such as gastric ulcer, duodenal ulcer and gastritis and other findings, and liver function in chronic liver disease. It has the effect of alleviating various symptoms such as improvement, and is widely used as a medicine.
  • MMSC has the property of decomposing by absorbing moisture in the air
  • formulations containing MMSC have problems of quality degradation such as odor generation, discoloration, and decrease in the effective component content. is doing. For this reason, many MMSC preparations are sugar-coated preparations for the purpose of preventing moisture absorption (Patent Documents 1 and 2).
  • sodium valproate is also used in various epilepsies such as minor seizures 'focus seizures' psychomotor seizures and mixed seizures, personality behavioral disorders associated with epilepsy (e.g., moodiness / anger), and manic and manic depression. It is widely used as a therapeutic drug.
  • sodium valproate has hygroscopicity and deliquescence, and is formulated as a sugar coating for the purpose of preventing quality degradation after opening (Patent Documents 3 and 4).
  • Sugar coating preparations are generally produced by repeating [1] spraying of sugar coating liquid, [2] steaming, and [3] drying several times (for example, Patent Document 5).
  • [2] steaming is a process for completely filling the side of the sugar-coating preparation and spreading the sprayed sugar-coating liquid evenly on the plain tablets.
  • a sugar-coating liquid having a high viscosity is used, This is an indispensable process.
  • the manufacturing method of a sugar-coating preparation including a complicated process has disadvantages such as requiring a very long working time and requiring a large amount of sugar-coating liquid for the uncoated tablet.
  • Patent Document 1 Japanese Patent Application Laid-Open No. 2003-63953
  • Patent Document 2 Japanese Patent Laid-Open No. 2003-95928
  • Patent Document 3 Japanese Patent Application Laid-Open No. 2006-256961
  • Patent Document 4 Japanese Patent Laid-Open No. 04-235914
  • Patent Document 5 Japanese Patent Laid-Open No. 06-292511
  • Patent Document 6 Japanese Patent Laid-Open No. 56-87518
  • Patent Document 7 Japanese Unexamined Patent Application Publication No. 2004-155656
  • Patent Document 8 JP-A-49-133515
  • An object of the present invention is to provide a technique for producing a sugar-coating preparation having sufficient hardness and excellent in low hygroscopicity, deodorizing property and disintegration in a short time and simply.
  • it has a sugar-coating liquid that can be suitably used for the production of a sugar-coating preparation using a continuous coating method in which the spraying process and the drying process of the sugar-coating liquid are simultaneously performed, and a sugar-coating layer formed from this sugar-coating liquid. It is an object to provide a sugar-coated preparation and a method for producing the same.
  • a sugar-coating liquid prepared by mixing ethyl acrylate and methyl methacrylate copolymer in a specific ratio in a solvent containing sugar has physical properties suitable for the continuous coating method, and a sugar-coating liquid having such a composition. It was found that a sugar-coating preparation having a sugar-coating layer formed by a continuous coating method using a liquid has low hygroscopicity, deodorization and good disintegration, and has completed the present invention.
  • the present invention is a sugar coating liquid containing sugar, ethyl acrylate 'methyl methacrylate copolymer and a solvent, and the concentration power of ethyl acrylate' methyl methacrylate copolymer is 0.01 to 10% by weight based on the total solid content.
  • a sugar-coating liquid, a method of producing a sugar-coating preparation using the sugar-coating liquid, and a sugar-coating preparation obtained by this production method are provided.
  • FIG. 1 is a graph showing changes in moisture absorption rate of a sugar-coated preparation over time.
  • FIG. 2 is a graph showing changes in moisture absorption rate of a sugar coating preparation containing a processed garlic product and time.
  • FIG. 3 is a graph showing the change in moisture absorption rate of the MMSC-containing sugar-coated preparation over time.
  • FIG. 4 A graph showing changes in moisture absorption of a sugar-coated preparation containing sodium pulp oleate with time.
  • FIG. 5 is a graph showing the change in elution rate of time and the pulp oleate sodium.
  • the sugar-coating liquid of the present invention contains sugar, ethyl acrylate acrylate methyl methacrylate copolymer, and a solvent.
  • the sugar used in the present invention is a sugar that is usually used for forming a sugar coating layer of a sugar coating preparation.
  • the amount of sugar is not particularly limited, but it is usually 10 to 85% by weight, preferably 10 to 70% by weight, more preferably 15 to 60% by weight.
  • Ethyl acrylate 'methyl methacrylate copolymer used in the present invention is a polymer obtained by copolymerization of ethyl acrylate and methyl methacrylate.
  • the number average molecular weight of the copolymer may be in a range that can impart appropriate hardness and disintegration to the sugar-coated preparation, but is usually 10,000 to 1,500,000, preferably ⁇ 400,000 to 1,200. , 000, more preferred ⁇ should be between 500,000 and 1,100,000.
  • the molar ratio of ethyl acrylate and methyl methacrylate constituting the copolymer is usually 10: 1 to 1:10, preferably 4: 1 to 1: 4, more preferably 3: 1 to 1: 3. It is good.
  • the glass transition temperature of the copolymer is usually in the range of 40-30 ° C, preferably 1-30-20 ° C, more preferably 1-20 ° C.
  • Ethyl acrylate 'methyl methacrylate copolymer can be obtained by copolymerizing ethyl acrylate and methyl methacrylate according to a conventional method.
  • a commercially available product may be used as the ethyl acrylate acrylate and methyl methacrylate copolymer.
  • Examples of commercially available products include Eudragit NE30D (Higuchi Shokai) and Kollicoat EMM30D (BASF Japan), which are emulsions in which ethyl acrylate 'methyl methacrylate copolymer is dispersed in water using a surfactant. .
  • the blending amount of ethyl acrylate acrylate / methyl methacrylate copolymer is 0.01 to 10% by weight based on the total solid content in the sugar coating liquid. Among these, Preferably it is 0.1 to 8 weight%. If the blending amount exceeds 10% by weight, it may be suspended in the sugar coating liquid and the solid content may be agglomerated, which is preferable.
  • the mass ratio of ethyl acrylate acrylate / methyl methacrylate copolymer and sugar is usually 1: 1 to 1: 10,000, preferably 1: 3 to 1: 1,000, more preferably 1: 5 to 1: It should be 500!
  • the solvent for the sugar coating liquid of the present invention is not particularly limited as long as it is usually used for sugar coating liquid.
  • water, lower alcohols such as ethanol and isopropanol, acetone or a mixture thereof can be used.
  • purified water is usually preferably used.
  • the amount of the solvent in the sugar coating liquid is not particularly limited, but it is usually 15 to 90% by weight, preferably 15 to 85% by weight, and more preferably 20 to 80% by weight. If the amount of solvent exceeds 90% by weight, the working time for forming the sugar-coated layer becomes longer, and it may be difficult to form a dense sugar-coated layer, which may stabilize the drug contained in the core material. May affect sex. If it is less than 15% by weight, the viscosity of the sugar-coating liquid may become high, and there may be problems in workability such as the tablets adhering to the pan of the tablet coating device, and when a sugar-coating preparation is produced by the continuous coating method.
  • the sugar coating liquid does not spread uniformly on the tablet surface, and a uniform sugar coating layer cannot be formed.
  • the viscosity of the sugar-coating liquid is not limited as long as it can be sprayed by an apparatus used for manufacturing a sugar-coating preparation, but is usually 3 to 1, 0 OOcp, preferably 5 to 700 cp, more preferably 10 to 400 cp. In this way, the amount of solvent can be adjusted.
  • the sugar coating liquid of the present invention can contain various optional components that are acceptable as pharmaceutical additives and can be administered orally as desired.
  • additives include coating agents, colorants, and brighteners.
  • the coating agent include hydroxypropyl cellulose, hydroxypropyl methenoresenorelose 2910, hydroxypropino methenoresenorelose 2208, methinoresenolose, polybulol alcohol, polybulurpyrrolidone, crystalline cellulose, gum arabic powder, fine powder.
  • Shellac, pullulan, precipitated calcium carbonate, talc, calcium hydrogen phosphate, light anhydrous caustic acid, hydrous silicon dioxide, titanium oxide, sodium dihydrogen phosphate, hydrogenated oil, glyceryl monostearate and polyethylene glycol monostearate The blending amount is preferably 0 to 80% by weight based on the sugar coating liquid.
  • colorant examples include various edible pigments, tar pigments, and iron sesquioxide, and the blending amount thereof is preferably 0.1% by weight or less with respect to the sugar coating preparation.
  • the brightening agent examples include carnauba wax and beeswax.
  • the amount of the brightening agent is preferably 0.1% by weight or less based on the sugar-coating preparation.
  • the viscosity of the sugar coating liquid of the present invention is usually 3 to 1, OOOcp, preferably 5 to 700 cp, and more preferably 10 to 400 cp. When a sugar coating solution having such a viscosity is used, it is easy to form a uniform sugar coating layer even when a sugar coating preparation is produced by a continuous coating method.
  • the sugar-coating liquid of the present invention can be produced by suspending sugar, ethyl acrylate / methyl methacrylate copolymer and, if necessary, the above optional components in a solvent. At this time, it is also preferable to add a surfactant in order to sufficiently disperse the ethyl acrylate / methyl methacrylate copolymer in the solvent.
  • the sugar-coated preparation of the present invention has at least one sugar-coated layer formed by using the sugar-coating liquid of the present invention around the core material containing the drug.
  • Examples of the core material containing the drug contained in the sugar-coated preparation of the present invention include uncoated tablets and core granules. That is, the sugar-coated preparation of the present invention can be made into a sugar-coated tablet or a sugar-coated granule, for example.
  • the drug contained in the core material is a drug that has been confirmed to be safe by oral administration, and is not particularly limited as long as it is suitable for a sugar coating preparation, but preferably has an unpleasant odor.
  • drugs with an unpleasant odor include herbal medicines (such as oxoamidin powder, hops, quinceins, assemblies, carrots, carrots, wikiweeds, chioji, shokiyo and funnel extracts), processed garlic products, methylmethionine sulfone. -Umchloride, L-cysteine, vitamin B, etc.
  • Vitamin D Vitamin D, vitamin E, piotin, calcium pantothenate, nicotinamide, vitamin P and its derivatives
  • methylmethionine sulfo-um chloride amino acids (such as aspartic acid and L-cysteine), adenosine Phosphate ⁇ Sodium salt, enzymes (starch digestive enzyme, protein digestive enzyme, fat digestive enzyme and fibrin digestive enzyme, etc.), sodium valproate, ibuprofen, guaifenesin and butyl scopolamine bromide
  • drugs that generate ibuprofen, anhydrous caffeine, ethenamide, isopropylantipyrine, and L-menthol examples of drugs that generate ibuprofen, anhydrous caffeine, ethenamide, isopropylantipyrine, and L-menthol.
  • the compounding amount of the product can be appropriately adjusted according to the use of the drug, but is preferably 0.1 to 99% by weight, more preferably 1 to
  • examples of the drug contained in the core material preferably include the following drugs.
  • the processed garlic is obtained by subjecting bulbs of the allium sativum 1.
  • the processing method is not particularly limited, for example, raw garlic dried and powdered, raw garlic extracted with steam distillation, oil, water, hot water or water-soluble organic solvent, raw garlic What was processed by heating etc. can be used.
  • the oil used for extraction include edible vegetable oils such as rapeseed oil, olive oil, and soybean oil.
  • the water-soluble organic solvent include lower alcohols such as ethanol and isopropanol; Daricol such as propylene glycol and diethylene glycol.
  • As the garlic processed product those obtained by pulverization after drying, those extracted with a lower alcohol, and those processed by heating are particularly preferred.
  • the processed garlic product may be a commercial product.
  • processed oak, garlic extract, nin-ta extract, dried garlic and the like are particularly preferred.
  • the processed oat is a garlic powder obtained by drying an extract obtained by extracting heat-treated garlic with a lower alcohol, for example, oxoamidin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.) and Oxo Resin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.) is on the market.
  • the Ninta extract include Ninta extract (Alps Yakuhin Kogyo Co., Ltd.), Nin-ku extract (Nippon Powder Yakuhin Co., Ltd.) and the like.
  • garlic powder and roasted garlic powder EX are commercially available.
  • oxoamidin registered trademark
  • oxoresin registered trademark
  • garlic extract alps
  • garlic extract Nippon Powder Chemical Co., Ltd.
  • the amount of garlic processed product can be adjusted as appropriate according to the use of the sugar-coating preparation, but it is preferably 2 to 30% by weight, more preferably 5 to 15% by weight based on the core material. .
  • Methylmethionine sulfone chloride can be obtained according to a known production method. Further, as a commercial product, for example, methylmethionine sulfo-um chloride (manufactured by Yonezawa Hamari Chemical Co., Ltd., manufactured by Alps Pharmaceutical Co., Ltd.) is commercially available.
  • the blending amount of MMSC is preferably 1 to 80% by weight, more preferably 10 to 40% by weight with respect to the core material.
  • the core material containing MMSC has a component that neutralizes gastric acid, a component that suppresses secretion of gastric acid (antacid component), a component that enhances stomach function (healthy stomach component), and assists digestion It is also preferable to further contain a component (digestive enzyme), a component that repairs the gastric mucosa (mucosal repair component), and the like.
  • the antacid component synthetic hydrotalsart, sodium hydrogen carbonate, magnesium aluminate metasilicate, sodium hydroxide-aluminum sodium carbonate coprecipitate, funnel extract, sodium hydroxide aluminum, sodium hydrogen carbonate, Magnesium carbonate, precipitated calcium carbonate, precipitated magnesium carbonate, dihydroxyaluminum aminoacetate, magnesium hydroxide, magnesium oxide, dried aluminum hydroxide gel, magnesium bismuth silicate, magnesium silicate, synthetic aluminum silicate, Latidine hydrochloride, cimetidine, famotidine, nizatidine, lafutidine, omebrazole, lansoprazole, pantoprazole, rabebrazole sodium, leminoprazole, esomeprazole, pirenzepine hydrochloride, proglumi And the like.
  • the components of healthy stomach include: assembly powder, hop extract, gentian extract, wikiyo powder, shokiyo powder, chiyouji powder, akamegashi powder powder, acenic powder powder, turmeric powder powder, ubai powder powder, wook powder powder, wogon powder powder End, Katsuko End, Kanzo End, Kikoku End, Kina End, Kuzin End, Keihi End, Kemi Mei End, Genno Shoko End, Koujin End, Kobota End, Goshu End, Gobai End, Colombo End, Chimpi End, Hawthorn End, Hawthorn End , Sanna powder, Soshishi powder, Stasha powder, Shozuk powder, Sehi powder powder, Sekishokon powder powder, Soujutsu powder powder, Soyo powder, Daio powder powder, Chikusennin powder powder, Spruce powder powder,-Gaki powder powder,-Kukuk powder powder, Carrot powder powder, Hikokoshi End, hihatsu
  • Digestive enzymes include biodiastase, lipase, ursodeoxycholic acid, Examples include pussin, diasmen, cellulase, cell mouth sine, takadiastase, bile powder, dehydrochol, neurase, pancreatin, biotamirase, prozyme, and polypase.
  • Mucosal repair ingredients include sucralfate, aldioxa, L-glutamine, sofalcone, copper black mouth fin sodium, copper black mouth fin potassium, cetraxate hydrochloride, gefarnate, trimebutine maleate, sodium azulensulphonate, etc. Can be mentioned.
  • Sodium valproate can be obtained according to a known production method (for example, JP-A-60-156638, JP-A-62-160441, JP-A-63-122646, JP-A-10-130197). No. publication).
  • sodium valproate manufactured by Nippon Synthetic Chemical Industry, manufactured by Facebook
  • the blending amount of sodium valproate is preferably 1 to 80% by weight, more preferably 30 to 60% by weight based on the core material.
  • various optional components that can be administered orally can be blended in the core material as desired.
  • various optional additives that can be administered orally include excipients, binders, disintegrants, lubricants, and the like.
  • excipients examples include lactose, crystalline cellulose, sucrose, mannitol, light anhydrous carboxylic acid, calcium hydrogen phosphate, and corn starch.
  • binder examples include methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, gelatin, polybutylpyrrolidone and pullulan.
  • disintegrant examples include carmellose calcium, low-substituted hydroxypropyl cellulose, crospovidone, and croscarmellose sodium.
  • Examples of the lubricant include magnesium stearate, calcium stearate and talc.
  • the core material used in the sugar-coated preparation of the present invention can be produced by a conventional method using a drug and other optional components.
  • a method of tableting the granulated product, or after granulating the drug to be blended and other optional additives are sized with a sizing machine to form powder, and if necessary, other optional additives are added to the powder and mixed to obtain powder, or these powders are tableted, or Examples thereof include a method in which a directly blended drug and other optional additives are mixed and tableted with a tableting machine.
  • examples of the granulation include a dry granulation method and a wet granulation method.
  • a powder is dry granulated without using a liquid such as water, ethanol, isopropanol, or a mixture thereof.
  • This is a method of producing a granular material by compression molding with a machine or the like to produce a plate-like solid material, and then breaking these.
  • the wet granulation method is a method in which a binding liquid is added to a powder by using a high speed stirring granulator, a kneading granulator, a fluidized bed granulator, a rolling fluid granulator, etc., to form particles.
  • the type of the binding solution is not particularly limited, but water, ethanol, isopropanol and a mixture thereof can be used.
  • the drug to be blended and other optional additives are granulated by a dry granulation method, a wet granulation method or a wet granulation method and an extrusion granulation method in combination.
  • a dry granulation method a wet granulation method or a wet granulation method and an extrusion granulation method in combination.
  • the method of condylar grain for example, the method of condylar grain.
  • At least one of the sugar coating layers covering the core material contained in the sugar coating preparation of the present invention is characterized in that it contains sugar and 0.01 to 10% by weight of ethyl acrylate / methyl methacrylate copolymer.
  • the sugar-coated preparation of the present invention has one or more coating layers formed of another coating liquid in addition to the one or more sugar-coated layers formed of the sugar coating liquid of the present invention. May be.
  • the layer formed from the sugar coating liquid of the present invention is referred to as “sugar coating layer”, and the layer formed from the sugar coating layer and the coating liquid other than the sugar coating liquid of the present invention is referred to as “coating layer”. May be described.
  • the covering layer is divided into a plurality of layers such as a protective layer, a subcoating layer, a smoothing layer, a coloring layer and a polishing layer according to the function. be able to.
  • the ratio of each of these layers to the entire coating layer is usually 0-20% for the waterproof layer, 15-100% for the undercoat layer, 0-50% for the midcoat layer, 0-50% for the overcoat layer, and the leach layer Is 0 to 10%.
  • a waterproof layer is applied to suppress moisture transfer to the core during the sugar coating process Is.
  • the undercoat layer is applied to shape the sugar-coated tablet, and the appearance and strength of the sugar-coated tablet are affected by the quality of the undercoat layer.
  • the intermediate layer is applied to smoothen the surface of the sugar-coated tablet, and the upper layer is colored to enhance the distinguishability and commercial value of the sugar-coated tablet.
  • the sugar-coated preparation of the present invention does not necessarily have to have all the coating layers having the above functions, but it is preferable to include a coating layer having the function of the undercoat layer.
  • the sugar-coating layer formed using the liquid can be suitably used as a coating layer having the function of an undercoat layer.
  • the sugar-coated preparation of the present invention can be covered with a release controlling layer in addition to the coating layer according to the purpose.
  • the release control layer is applied to give a function of controlling the dissolution of the drug contained in the core material, and may be one or a plurality of layers.
  • the release control layer can be applied directly to the core material, or it can be applied between any of the waterproof layer, undercoat layer, intermediate coat layer, overcoat layer, and leach layer. It is preferable to coat the core material.
  • 1 to 10% by weight is more preferable with respect to 1 part by weight of the sugar-coating preparation, more preferably 2 to 8% by weight.
  • conventional methods can be used as the method for applying the release controlling layer and the components used.
  • the weight of the sugar coating layer formed using the sugar coating liquid of the present invention in the sugar coating preparation of the present invention is preferably 5 to 60% by weight, more preferably 10 to 50% by weight, based on the weight of the core material. is there. If the weight of the sugar-coating layer exceeds 60% by weight, the coating process takes longer time, and the mass of the finished sugar-coating preparation increases with respect to the mass of the core material charged, resulting in the need for a separate coating device. . If the amount is less than 5% by weight, sufficient coating layer hardness cannot be obtained, and the coating layer is too thin to protect the contents such as uncoated tablets or core granules from environmental humidity. May occur.
  • the moisture absorption rate in the sugar-coated preparation of the present invention is preferably 1.0% or less, more preferably 0.5% or less under the conditions after 24 hours at a temperature and humidity of 25 ° C -85%. Under the condition after 30 days at a humidity of 40 ° C.-75%, it is preferably 4.0% or less, more preferably 3.0% or less.
  • the hardness and the degree of disintegration can be appropriately adjusted according to the intended use of the sugar-coated preparation of the present invention and the drug contained in the core material.
  • the hardness of the sugar-coated preparation is preferably 100N or more, more preferably 110N or more.
  • the degree of disintegration is preferably within 25 minutes.
  • the hardness of the sugar-coated preparation is preferably 65 N or more, more preferably 70 N or more.
  • the disintegration degree is preferably within 15 minutes.
  • the hardness of the sugar-coating preparation is preferably 65 N or more, more preferably 70 N or more.
  • the sugar-coated preparation of the present invention can be produced by forming a sugar-coated layer by a continuous coating method in which the step of spraying the sugar-coating liquid of the present invention and the drying step are simultaneously performed. That is, by spraying the sugar-coating liquid of the present invention on the core material containing the drug, drying is carried out, so that the solvent in the sugar-coating liquid covering the core material can be removed to form a sugar-coating layer. Also, depending on the core material used (plain tablet or core granule), a sugar-coated tablet or sugar-coated granule can be prepared.
  • a sugar coating layer covering the core material can be formed.
  • equipment used for the continuous coating method include a Neucoater (Freund Sangyo), Aqua Coater (Freund Sangyo), Palleta Coater (Paulek), and Doria Coater (Paulek).
  • the droplet size of the sugar coating liquid to be sprayed is preferably 0.1 to 1,000 m.
  • the spray amount is preferably adjusted to spread over the entire surface of the core material according to the size and amount of the core material. .
  • the temperature of the sugar coating liquid is preferably 10 to 80 ° C. It is preferable to adjust the supply air temperature and air volume so that the product temperature is 10-60 ° C! /.
  • a fluidized bed coating machine When producing sugar-coated granules, it is preferable to use a fluidized bed coating machine, and it is particularly desirable to use a rolling fluidized bed coating machine having a rotating disk at the bottom.
  • a fluidized bed coating machine For example, multiplex (Paurek), Darreux (Freund industry), Spiraflow (Freund industry), Agromaster (Hosokawamicron), and Numeralizer (non-nipadal).
  • Granules containing drugs in a coating device whose bottom surface of the main body rotates continuously, or Protease-coated granules with a waterproof layer, etc. are introduced, and a sugar coating layer covering the core material is formed by simultaneously spraying and drying the sugar coating liquid on the granules that flow and rotate in the apparatus or the protection-coated granules. be able to.
  • the droplet size of the sugar-coating liquid to be sprayed should be adjusted to 0.1 to LOO m so that the spray amount spreads over the entire surface of the core material according to the size and amount of the core material.
  • the temperature of the sugar coating liquid is preferably 10 to 80 ° C. It is preferable to adjust the supply air temperature and air volume so that the product temperature is 10-50 ° C.
  • the formation of the coating layer with a coating solution other than the sugar coating solution of the present invention can be carried out by a method generally used in the manufacture of sugar coating preparations.
  • the coating apparatus used at this time can be appropriately selected and used depending on the type of the coating solution, and is not particularly limited.
  • the droplets and spray amount when spraying the coating liquid can be adjusted in the same manner as the spraying of the sugar coating liquid.
  • the sugar-coated preparation of the present invention thus obtained has a sufficient hardness that the sugar-coated layer is thin compared to conventional preparations, and is excellent in low moisture absorption, deodorization and disintegration.
  • Lactose 3000g, hydroxypropylcellulose (HPC—L: Nippon Soda) 150g, corn starch 1200g, crystalline cellulose (Ceras PH—101: Asahi Kasei) lOOOg was put into a high-speed agitation granulator (VG—25: Baurek) and purified.
  • a granulated product was prepared by adding water. This was dried with a fluidized bed dryer (FLO-5B: Freund Sangyo), and then the dried product was sized with a sizing machine (Pair Mill, Showa Chemical Machinery).
  • the suspension was coated with a sugar coating liquid (Driacoater DRC-650, Norrec) and dried while spraying the sugar coating liquid to obtain 375 mg sugar coated tablets per tablet.
  • the suspension was coated with a sugar coating liquid (Driacoater DRC-650, Bauch) and dried while spraying the sugar coating liquid to obtain 375 mg sugar coated tablets per tablet. The time spent for the coating work was 2 hours.
  • the suspension was coated with a sugar coating liquid (Driacoater DRC-650, Norrec) and dried while spraying the sugar coating liquid to obtain 375 mg sugar coated tablets per tablet. The time spent on the coating work was 2 hours.
  • Suspended dragee solution consisting of 5160 g of protected latch obtained in Production Example 1, 1160 g of granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, 40 g of hydroxypropylmethylcellulose 2910 (TC-5R: Shin-Etsu Chemical Co., Ltd.) and 2000 g of purified water
  • a coating machine Drycoater DRC-650, Norrec
  • the sugar coating solution was sprayed and dried to obtain 375 mg sugar coated tablets per tablet.
  • the time spent on coating is 2 hours. It was.
  • Protected tablet 5500g obtained in Production Example 1 was added to granulated sugar 1924g, talc 542g, precipitated canoresium carbonate 818g, gum arabic 64g, gelatin 30g, polyoxyethylene (105) polyoxypropylene (5) glycol (PEP-101: Freund Sangyo Co., Ltd.
  • a conventional sugar coating that uses a sugar coating liquid suspended in 22 g and 120 Og of purified water, and sprays, steams and drys the sugar coating liquid separately in a coating machine (Driacoater DRC-650, Paurek). According to the method, 445 mg of sugar-coated tablets were obtained per tablet. The time spent for the coating work was 6.5 hours.
  • Protected tablet 5500g obtained in Production Example 2 granulated sugar 1180g, talc 400g, precipitated calcium carbonate 400g, ethyl acrylate 'methyl methacrylate copolymer 30% dispersion (Eudragit NE30D: Higuchi Shokai) 66.7g and purified water 2000g
  • the sugar coating liquid is sprayed with a coating machine (Driacoater DRC-650, Norec) using the suspended sugar coating liquid consisting of Drying was carried out while fogging to obtain 375 mg sugar-coated tablets per tablet.
  • the time spent on the coating work was 2 hours.
  • Protected tablet 5500 g obtained in Production Example 2 granulated sugar 1160 g, talc 400 g, precipitated calcium carbonate 400 g, ethyl acrylate “methyl methacrylate copolymer 30% dispersion (Eudragit NE30D: Higuchi Shokai) 133.3 g and purified water 2000 g
  • the suspension was coated with a sugar coating liquid (Driacoater DRC-650, Norrec) and dried while spraying the sugar coating liquid to obtain 375 mg sugar coated tablets per tablet.
  • the time spent on the coating work was 2 hours.
  • Protected tablet 5500g obtained in Production Example 2 Granulated sugar 1120g, Talc 400g, Precipitated calcium carbonate 400g, Ethyl acrylate 'Methyl methacrylate copolymer 30% dispersion (Eudragit NE30D: Higuchi Shokai) 266.7g and purified water 2000g
  • the suspension was coated with a sugar coating liquid (Driacoater DRC-650, Norrec) and dried while spraying the sugar coating liquid to obtain 375 mg sugar coated tablets per tablet.
  • the time spent on the coating work was 2 hours.
  • Suspended sugar-coating liquid consisting of 1160 g of granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, 40 g of hydroxypropylmethylcellulose 2910 (TC-5R: Shin-Etsu Chemical Co., Ltd.) and 2000 g of purified water
  • a coating machine Drycoater DRC-650, Norrec
  • the sugar coating solution was sprayed and dried to obtain 375 mg sugar coated tablets per tablet.
  • the time spent on the coating work was 2 hours.
  • Protected tablet 5500g obtained in Production Example 2 granulated sugar 1924g, talc 542g, precipitated canoresium carbonate 818g, gum arabic 64g, gelatin 30g, polyoxyethylene (105) polyoxypropylene (5) glycol (PEP-101: (Freund Sangyo Co., Ltd.)
  • a coating machine (Driacoater DRC-650 The sugar coating liquid was sprayed, steamed, and dried separately in Ulek), and 445 mg of sugar-coated tablets were obtained per tablet. The time spent for the coating work was 6.5 hours.
  • Methylmethioninesulfo-umchloride lOOOg (Methylmethiononesulfo-umchloride, Yonezawa Hamariyaku), lactose 600g, polybylpyrrolidone (Kollidon 30: BASF Japan) 300g, corn starch 1550g, carmellose calcium (ECG- 505: Gotoku (Pharmaceutical) 500g was put into a high-speed agitation granulator (VG-25: Paurek), and the granulated product was prepared by covering with ethanol. This was dried with a fluidized bed dryer (FLO-5B: Freund Sangyo), and then dried with a granulator (Power Mill, Showa Chemical Machinery).
  • FLO-5B Freund Sangyo
  • Protected lock obtained in Production Example 3 4800g, Granulated sugar 1180g, Talc 400g, Precipitated calcium carbonate 400g, Ethyl acrylate 'Methyl methacrylate copolymer 30% dispersion (Eudragit NE30D: Higuchi Shokai) 66.7g and purified water 2000g Using the sugar coating liquid suspended from the above, drying was performed while spraying the sugar coating liquid with a coating machine (Driacoater DRC-650, Norrec) to obtain 170 mg sugar coated tablets per tablet. The time spent on the coating work was one hour.
  • Protected tablet 4800g obtained in Production Example 3 was added to 1160g of granulated sugar, 400g of talc, 400g of precipitated calcium carbonate, 30% dispersion of ethyl acrylate and methyl methacrylate copolymer ( Eudragit NE30D: Higuchi Shokai) 133.
  • a suspension of sugar coating liquid consisting of 3 g and 2000 g of purified water, dry it while spraying the sugar coating liquid on a coating machine (Driacoater DRC-650, Norrec). 170 mg dragees were obtained per tablet. The time spent on the coating work was one hour.
  • Protected lock obtained in Production Example 3 4800g, Granulated sugar 1120g, Talc 400g, Precipitated calcium carbonate 400g, Ethyl acrylate 'Methyl methacrylate copolymer 30% dispersion (Eudragit NE30D: Higuchi Shokai) 266. 7g and purified water 2000g A coating machine (Driacoater DRC-650,
  • the powder was dried while spraying the sugar-coating liquid at REC) to obtain 170 mg of sugar-coated tablets per tablet.
  • the time spent on the coating work was one hour.
  • Suspended sugar-coating liquid consisting of 1800 g of granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, 40 g of hydroxypropylmethylcellulose 2910 (TC-5R: Shin-Etsu Chemical Co., Ltd.) and 2000 g of purified water.
  • a coating machine Drycoater DRC-650, Norec
  • the time spent on the coating work was one hour.
  • the suspended sugar coating liquid consisting of 660 g of granulated sugar, 1100 g of talc, 1100 g of precipitated calcium carbonate, 280 g of gum arabic, 60 g of gelatin and 600 g of purified water, DRC-650, Norec
  • the time spent on the coating work was 3.5 hours.
  • a controlled release layer After applying a controlled release layer to the uncoated tablet using a coating machine (Driacoater DRC-6650, Norec), 60 g of ethyl cellulose and 30 g of light caustic anhydride were further dissolved in 141 Og of ethanol. Using the dispersed liquid, a controlled release layer was applied with a coating machine (Driacoater DRC-650, Purreck) to produce 245 mg controlled release tablets per tablet.
  • a coating machine Driacoater DRC-6650, Norec
  • a conventional sugar coating liquid consisting of 114 g of granulated sugar, 6 g of acid oxytitanium and 72 g of purified water is used to spray, steam and dry the sugar coating liquid separately on a small sugar coating machine (manufactured by Kikusui Seisakusho) According to the sugar coating method, 455 mg colored tablets per tablet were obtained. The time spent for this coating operation was 240 minutes.
  • a sugar coating liquid consisting of 15g of granulated sugar and 9g of purified water, spraying, steaming and drying the sugar coating liquid separately using a small sugar coating machine (manufactured by Kikusui Seisakusho) Dragee tablets (of which the sugar coat layer mass was 215 mg) were obtained. The time spent on this coating operation was 30 minutes, and the total time spent on all coating operations was 570 minutes.
  • the use of the production method of the present invention in which drying is performed simultaneously with spraying the sugar coating liquid can reduce the working time to one third or less compared with the conventional coating method. It was.
  • the weight of the sugar-coated layer in sugar-coated tablets can be reduced to about one-half to one-fourth.
  • Moisture absorption (%) (10 tablet weight after storage for each time-10 tablet weight at the start) Z 10 tablet weight at the start X 100
  • the sugar-coated preparations of Examples 1 to 3 had a low moisture absorption rate of 0.1% even when allowed to stand for 24 hours under the above conditions.
  • the sugar-coated preparation of Comparative Example 1 had a moisture absorption rate of 0.2% when allowed to stand for 3 hours, and increased to nearly 1.2% when allowed to stand for 24 hours.
  • Comparative example The sugar coating formulation of No. 2 increased the moisture absorption rate to about 0.5% when allowed to stand for 24 hours.
  • the sugar-coated preparations of Examples 4 to 6 showed a low moisture absorption rate of 0.1% even when allowed to stand for 24 hours under the above conditions.
  • the sugar-coated preparation of Comparative Example 3 had a moisture absorption rate of 0.4% when allowed to stand for 3 hours, and increased to nearly 2.1% when allowed to stand for 24 hours.
  • the sugar-coated preparation of Comparative Example 4 increased the moisture absorption rate to about 0.5% when allowed to stand for 24 hours.
  • the sugar-coated preparations of Examples 7 to 9 and Comparative Example 6 showed a low moisture absorption rate of 0.5% or less even when allowed to stand for 24 hours under the above conditions.
  • the sugar-coated preparation of Comparative Example 5 increased its moisture absorption rate to near 1.3% when left for 3 hours, and increased to near 5.6% when left for 24 hours.
  • the sugar-coated preparations of Examples 10 and 11 have a moisture absorption rate after 30 days, although the sugar-coated layer mass is about one-quarter and one-half that of Comparative Example 7, respectively. However, they were extremely low at 2.0% and 1.0% or less, respectively.
  • the sugar-coated preparation of Comparative Example 7 had a moisture absorption rate of nearly 4.0% after 7 days, and the tablet burst after 10 days. The rupture of the tablet is presumed to be due to the hygroscopic nature of sodium levoleate.
  • the sugar-coating liquid of the present invention when used, even when a sugar-coating preparation is produced by a coating method in which the sugar-coating liquid is dried while spraying the sugar-coating liquid, the sugar-coating is excellent in low hygroscopicity compared with the conventional sugar-coating preparation. It was possible to obtain a formulation.
  • the hardness and disintegration degree of the sugar-coated tablets obtained in Examples 1 to 9 and Comparative Examples 1 to 6 were measured.
  • the hardness was 20 tablets, and the tablet hardness was measured with a tablet hardness meter (PTB-311E manufactured by PHARMATEST) for each tablet, and the average value was calculated.
  • the degree of disintegration was measured using an auxiliary panel according to the disintegration test method described in the 15th revision of the Japanese Pharmacopoeia (disintegration tester manufactured by Toyama Sangyo Co., Ltd.). The test was conducted on 6 tablets and the average value was calculated. The results are shown in Tables 1-3.
  • Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Hardness (N) 1 20.2 0.2 4 4 6 1 1 6. 1 7 1 .6 1 4 2 .7 Disintegration degree (min) 2 2 .4 2 1 .0 2 0 .6 2 9 .9 3 0 .9 [0063]
  • the sugar-coated preparations of Examples 1 to 3 had sufficient hardness and excellent disintegration properties.
  • the sugar-coated preparation of Comparative Example 1 was insufficient in both hardness and disintegration.
  • the sugar coating preparation of Comparative Example 2 had a high hardness and a poor disintegration property.
  • Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Hardness (N) 1 1 8. 5 1 20. 3 1 2 5. 8 9 1. 8 1 3 8.5 Disintegration (min) 2 0. 5 2 2. 3 2 1. 9 2 8. 3 3 2. 1
  • the sugar-coated preparations of Examples 4 to 6 had sufficient hardness and excellent disintegration properties.
  • the sugar-coated preparation of Comparative Example 3 was insufficient in both hardness and disintegration.
  • the sugar-coating preparation of Comparative Example 4 had high and hardness! /, And the disintegration property was insufficient.
  • Example 7 Example 8 Example 9 Comparative Example 5 Comparative Example 6 Hardness (N) 7 2. 8 7 6. 5 8 1. 8 5 9. 8 9 2.9 Disintegration degree (min) 1 2. 1 1 1 .5 1 2. 2 1 1. 9 1 8. 5
  • the sugar-coated preparation of the present invention has sufficient hardness and excellent disintegration properties.
  • Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Immediately after production 0 0 0 0 0 0 0
  • Example 7 Example 8
  • Example 7 Example 8
  • Example 9 Comparative example 5 Comparative example 6
  • Moisture value (%) 1.6 5 1.5 5 5 5 1.6 2 1.5 5 6 2.4 8
  • the dissolution test of the sugar-coated tablets of Example 11 was performed. The test was conducted at lOOrpm per minute using the Japanese Pharmacopoeia Dissolution Test Method 2 (Paddle Method) using 500 mL of the Japanese Pharmacopoeia General Test Method Disintegration Test Method 2 as the test solution. Sampling was performed every hour, and sodium valproate in the sampling solution was quantified by HPLC, and the elution rate (%) of sodium pulp oleate was calculated. The results are shown in FIG.
  • FIG. 5 shows that the sugar-coated preparation of the present invention is also excellent in sustained release properties.
  • the sugar-coating liquid of the present invention is also useful for making a sugar-coating preparation of a drug that requires sustained release.
  • the sugar-coated preparation of the present invention is a preparation that has sufficient hardness and is excellent in low hygroscopicity and deodorization as compared with conventional sugar-coated preparations produced by a continuous coating method. Compared with conventional sugar-coating preparations manufactured by the method, it was found that the preparations can be manufactured with a short coating process, have a low water content immediately after manufacture, and have excellent disintegration properties.
  • a sugar-coating preparation having sufficient hardness despite its thin sugar-coating layer and excellent in low moisture, low hygroscopicity, disintegration, and deodorization immediately after production can be obtained in a short time. And it can manufacture easily.
  • the sugar-coating liquid of the present invention By using the sugar-coating liquid of the present invention, it is possible to produce a sugar-coating preparation by a continuous coating method in which the spraying process and the drying process of the sugar-coating liquid are performed simultaneously. That is, a sugar-coating preparation excellent in low oxygen permeability, low hygroscopicity, deodorization and disintegration can be produced in a short time without requiring a complicated process.
  • the production method of the present invention forms a thin sugar coating layer. Therefore, it greatly contributes to reducing the amount of sugar-coating liquid used and miniaturizing the preparation.

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Abstract

L'invention concerne une technique de fabrication d'une préparation enrobée de sucre présentant une dureté suffisante et faible absorption d'humidité, une propriété désodorisante et une désintégration facile et rapide. De façon spécifique, l'invention concerne un liquide d'enrobage de sucre utilisé, de préférence, dans la fabrication d'une préparation enrobée de sucre à l'aide d'un procédé d'enrobage en continu dans lequel une étape de pulvérisation du liquide d'enrobage de sucre et une étape de séchage sont conduites simultanément, une préparation enrobée de sucre avec une couche d'enrobage de sucre formée par le liquide d'enrobage de sucre ainsi qu'un procédé de fabrication de ladite préparation. La préparation enrobée de sucre est obtenue à l'aide du liquide d'enrobage de sucre contenant un copolymère acrylate d'éthyle/méthacrylate de méthyle et un solvant, la concentration du copolymère acrylate d'éthyle/méthacrylate de méthyle étant de 0,01 à 10 % en poids sur la base du composant solide total.
PCT/JP2007/064152 2006-07-25 2007-07-18 Préparation enrobée de sucre et son procédé de fabrication WO2008013084A1 (fr)

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JP2008526734A JPWO2008013084A1 (ja) 2006-07-25 2007-07-18 糖衣製剤およびその製造方法
CN2007800281535A CN101495101B (zh) 2006-07-25 2007-07-18 糖衣制剂及其制造方法
HK09110763.5A HK1132664A1 (en) 2006-07-25 2009-11-17 Sugar-coated preparation and process for producing the same

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Publication number Priority date Publication date Assignee Title
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
CN104367625A (zh) * 2014-11-03 2015-02-25 成都森科制药有限公司 夏枯草片的制备方法

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FR3067567B1 (fr) * 2017-06-19 2019-07-05 Roquette Freres Nouveau procede de drageification et formes solides drageifiees presentant des formes irregulieres

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WO2004108164A1 (fr) * 2003-06-04 2004-12-16 Kyowa Hakko Kogyo Co., Ltd. Composition d'enrobage et preparation enrobee
WO2005039542A1 (fr) * 2003-10-27 2005-05-06 Yamanouchi Pharmaceutical Co., Ltd. Microparticule enrobee contenant un medicament pour comprime a dissolution orale
WO2005120466A2 (fr) * 2004-06-07 2005-12-22 Wyeth Enrobages drageifies et procedes permettant de produire ces enrobages drageifies

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JPS5244224A (en) * 1975-10-01 1977-04-07 Yamanouchi Pharmaceut Co Ltd Printing on sugar-coated tablets
CH666405A5 (de) * 1985-06-24 1988-07-29 Ciba Geigy Ag Feste, haltbare darreichungsformen mit elastischem filmueberzug.
JPS64421A (en) * 1987-06-23 1989-01-05 Kurita Water Ind Ltd Flow rate measuring instrument
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JPS5163926A (en) * 1974-10-17 1976-06-02 Roehm Gmbh Shokyujoyakuzaino seiho
JP2004010611A (ja) * 2002-06-06 2004-01-15 Nisshin Yakuhin Kogyo Kk マスキング組成物
WO2004108164A1 (fr) * 2003-06-04 2004-12-16 Kyowa Hakko Kogyo Co., Ltd. Composition d'enrobage et preparation enrobee
WO2005039542A1 (fr) * 2003-10-27 2005-05-06 Yamanouchi Pharmaceutical Co., Ltd. Microparticule enrobee contenant un medicament pour comprime a dissolution orale
WO2005120466A2 (fr) * 2004-06-07 2005-12-22 Wyeth Enrobages drageifies et procedes permettant de produire ces enrobages drageifies

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Publication number Priority date Publication date Assignee Title
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
WO2012029348A1 (fr) * 2010-08-31 2012-03-08 協和発酵キリン株式会社 Granulés contenant un médicament amer et comprimé à désintégration orale
CN104367625A (zh) * 2014-11-03 2015-02-25 成都森科制药有限公司 夏枯草片的制备方法

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