WO2008013084A1 - Sugar-coated preparation and process for producing the same - Google Patents

Abstract

A technique for producing a sugar-coated preparation which has sufficient hardness and is excellent in low moisture absorption, a deodorizing property and disintegratability easily in a short time is provided. Specifically, a sugar-coating liquid which can be preferably used in the production of a sugar-coated preparation using a continuous coating method in which a step of spraying the sugar-coating liquid and a drying step are simultaneously conducted, a sugar-coated preparation with a sugar-coating layer formed with the sugar-coating liquid, and a process for producing the same are provided. The sugar-coated preparation is produced using the sugar-coating liquid containing an ethyl acrylate/methyl methacrylate copolymer and a solvent wherein the concentration of the ethyl acrylate/methyl methacrylate copolymer is 0.01 to 10% by weight based on the total solid component.

Description

 Specification

 Sugar coating preparation and method for producing the same

 Technical field

 [0001] The present invention relates to a sugar-coated preparation and a method for producing the same.

 Background art

 [0002] 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.

 [0003] For example, 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. However, because 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. However, 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).

[0004] 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). Of these, [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. Usually, when a sugar-coating liquid having a high viscosity is used, This is an indispensable process. On the other hand, like this 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.

 [0005] As a production method for overcoming the above disadvantages, a method of forming a coating layer by drying while spraying a coating liquid, as in the production of a film-coated tablet (hereinafter also referred to as a continuous coating method). ), A method of forming a sugar coating layer is being studied. In the continuous coating method, since the sprayed sugar coating solution must be spread quickly and uniformly on a core material such as an uncoated tablet, it is required to dilute the sugar coating solution to reduce the viscosity. Therefore, for example, a technique for forming a thin sugar coating layer using a sugar coating solution in which sugar and talc are suspended has been developed (Patent Document 6). However, such a thin sugar-coated layer has a problem that it is inferior in strength to the conventional product. In addition, as a method for improving the strength of the thin sugar coating layer, for example, a technique of providing an intermediate layer between the film-coated tablet and the sugar coating layer has been developed (Patent Document 7). However, such a method is difficult to say because it involves the preparation and spraying of a coating solution having a composition different from that of the sugar coating layer. In addition, a technique for reducing the viscosity of a sugar coating liquid by using hydroxypropylmethylcellulose or hydroxypropylcellulose instead of gum arabic or gelatin usually used as a binder has been developed (Patent Document 8). However, the sugar-coated layer obtained by this method has a problem that it is inferior in low oxygen permeability, low hygroscopicity, and deodorizing properties, which are characteristics of a sugar-coated preparation that is not sufficiently dense.

 As described above, various investigations have been made on the method for producing a sugar-coating preparation and the sugar-coating liquid from the viewpoint of improving workability and the characteristics of the preparation, but a technology for improving both of them has not been developed yet.

[0006] 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

 Disclosure of the invention

 [0007] 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. Specifically, 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.

 [0008] The present inventors have conducted various studies on the composition of a sugar coating liquid suitable for the continuous coating method. 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.

 That is, 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. Brief Description of Drawings

[0009] 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.

 BEST MODE FOR CARRYING OUT THE INVENTION

[0010] 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. Can be used without limitation, and examples thereof include granulated sugar, purified sucrose, sucrose, glucose, toreno, and loin. Of these, granulated sugar, purified sucrose, and sucrose are preferably used.

 In the sugar coating liquid of the present invention, 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.

[0011] 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. Further, 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. .

 In the sugar coating liquid of the present invention, 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.

 In the sugar coating liquid of the present invention, 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!

[0012] 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. Not. For example, water, lower alcohols such as ethanol and isopropanol, acetone or a mixture thereof can be used. Of these solvents, 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. In some cases, 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.

 In addition to the above-described components, 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. Examples of such additives include coating agents, colorants, and brighteners. Examples of 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.

 Examples of the colorant 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.

Examples of the brightening agent 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. [0014] 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.

[0015] 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.

 In the present invention, 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 that have moisture, drugs that are unstable to water, and drugs that generate whiskers. For example, 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.

 1

 (Vitamin A, Vitamin B, Vitamin B, Vitamin B, Vitamin B, Vitamin C

 1 2 6 12

, 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 Examples of drugs that generate ibuprofen, anhydrous caffeine, ethenamide, isopropylantipyrine, and L-menthol. These drugs 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 85% by weight based on the core material.

In the present invention, examples of the drug contained in the core material preferably include the following drugs.

 [Processed garlic]

 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. Examples of the oil used for extraction include edible vegetable oils such as rapeseed oil, olive oil, and soybean oil. Examples of 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. For example, processed oak, garlic extract, nin-ta extract, dried garlic and the like are particularly preferred. Here, 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. Examples of the Ninta extract include Ninta extract (Alps Yakuhin Kogyo Co., Ltd.), Nin-ku extract (Nippon Powder Yakuhin Co., Ltd.) and the like. For example, garlic powder and roasted garlic powder EX (manufactured by Riken Igaku Kogyo Co., Ltd.) are commercially available. Among these commercially available garlic products, oxoamidin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.), oxoresin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.), garlic extract (alps) Yakuhin Kogyo Co., Ltd.) and garlic extract (Nippon Powder Chemical Co., Ltd.) are preferred. 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] Methylmethionine sulfo-um chloride (MMSC) 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.

 [0018] In addition, 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.

 [0019] As 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 powder, Daio powder powder, Chikusennin powder powder, Spruce powder powder,-Gaki powder powder,-Kukuk powder powder, Carrot powder powder, Hikokoshi End, hihatsu end, biakujutsu end, mokkou end, yakchi end, yono kuhihi end, hat power , Gentian powder, ryokuki powder, varnished fruit, aloe, sweet potato, daiwi quill, tundurangia, processed potato, calamus root, centaulium grass, honey extract, dry yeast, carcin chloride, glutamic acid, salted betanechol, trimebutine maleate, etc. Is mentioned. 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.

[0020] [Sodium parbromate]

 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). As commercial products, for example, sodium valproate (manufactured by Nippon Synthetic Chemical Industry, manufactured by Alibaba) is commercially available. 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.

 [0021] In addition to the above drugs, various optional components that can be administered orally can be blended in the core material as desired. Examples of such various optional additives that can be administered orally include excipients, binders, disintegrants, lubricants, and the like.

 Examples of excipients include lactose, crystalline cellulose, sucrose, mannitol, light anhydrous carboxylic acid, calcium hydrogen phosphate, and corn starch.

 Examples of the binder include methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, gelatin, polybutylpyrrolidone and pullulan. Examples of the disintegrant include carmellose calcium, low-substituted hydroxypropyl cellulose, crospovidone, and croscarmellose sodium.

 Examples of the lubricant include magnesium stearate, calcium stearate and talc.

 [0022] 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.

For example, in the case of an uncoated tablet, after granulating the drug to be blended and other optional additives, a method of tableting the granulated product, or after granulating the drug to be blended and other optional additives, These 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.

 Here, examples of the granulation include a dry granulation method and a wet granulation method. In the dry 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. In the method for carrying out the drying, the type of the binding solution is not particularly limited, but water, ethanol, isopropanol and a mixture thereof can be used.

 [0023] Next, in the case of a core granule, 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. 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.

 [0024] In addition, 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. In the present specification, 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. In addition, 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.

 [0025] Furthermore, 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. When covering the controlled release layer, 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. In addition, conventional methods can be used as the method for applying the release controlling layer and the components used.

 [0026] 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.

 [0027] 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. In addition, 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.

When the core material of the sugar-coated preparation of the present invention contains processed garlic, 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.

 In the case where the core material SMMSC of the sugar-coated preparation of the present invention is contained, 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. When the core material of the sugar-coating preparation of the present invention contains sodium pulp oleate, the hardness of the sugar-coating preparation is preferably 65 N or more, more preferably 70 N or more.

 [0028] 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.

 [0029] When a sugar-coated tablet is manufactured, an uncoated tablet containing a drug or a protective lock with a waterproof layer or the like is placed in a continuously rotating coating apparatus, and the uncoated tablet or protect rotating within the apparatus By simultaneously spraying and drying the sugar coating liquid on the hanging lock, a sugar coating layer covering the core material can be formed. Examples of 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! /.

 [0030] 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. 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.

[0031] 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. In addition, 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.

 Example

 Hereinafter, the present invention will be specifically described with reference to examples.

 <Production example 1>

 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).

50350 g of magnesium stearate was mixed with 5350 g of the obtained granulated product, and 270 mg of uncoated tablets were produced per tablet using a rotary tableting machine (HP-AP18-SS: Hata Kyosho). Using a coating solution consisting of 100 g of hydroxypropylmethylcellulose 2910 (TC-5R: Shin-Etsu Chemical Co., Ltd.) and 900 g of purified water on 5400 g of uncoated tablet, a waterproof layer is applied to the uncoated tablet using a coating machine (Drier Coater DRC-650, Norrec). 275mg per tablet Protective lock was manufactured.

 <Example 1>

 Protected tablet 5500g obtained in Production Example 1, 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 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.

 <Example 2>

 Protected tablet 5500g obtained in Production Example 1, Granulated sugar 1160g, Talc 400g, Precipitated calcium carbonate 400g, Ethyl acrylate 'Methyl methacrylate copolymer 30% dispersion (Eudragit NE30D: Higuchi Shokai) 133. 3g and purified water 2000g 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.

 <Example 3>

 Protected tablet 5500g obtained in Production Example 1, 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.

 <Comparative Example 1>

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 Using 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.

 [0037] <Comparative Example 2>

 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.

[0038] <Production example 2>

 Nin-Takae 500g (Oxoamidin, Riken Igaku Kogyo Co., Ltd.), Lactose 2500g, Hydroxypropylcellulose (HPC—L: Nippon Soda) 150g, Corn starch 1200g, Crystalline cellulose (Chorus PH—101: Asahi Kasei) lOOOg was put into a high-speed agitation granulator (VG-25: Norec) and purified water was added to prepare a granulated product. This was dried with a fluidized bed dryer (FLO-5B: Freund Sangyo), and then the dried product was sized with a granulator (Power Mill, Showa Chemical Machinery).

 50350 g of magnesium stearate was mixed with 5350 g of the obtained granulated product, and 270 mg of uncoated tablets were produced per tablet using a rotary tableting machine (HP-AP18-SS: Hata Kyosho). Using a coating solution consisting of 100 g of hydroxypropylmethylcellulose 2910 (TC-5R: Shin-Etsu Chemical Co., Ltd.) and 900 g of purified water on 5400 g of uncoated tablet, a waterproof layer is applied to the uncoated tablet using a coating machine (Drier Coater DRC-650, Norrec). Protected locks of 275 mg per tablet were produced.

 <Example 4>

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.

 [0040] <Example 5>

 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.

 [0041] <Example 6>

 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.

 [0042] <Comparative Example 3>

 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 Using 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.

 <Comparative Example 4>

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.

[0044] <Production Example 3>

 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).

 50g of magnesium stearate was mixed with 3950g of the obtained sized product, and lOOmg of uncoated tablets per tablet was produced using this with a rotary tableting machine (HP-AP18-SS: Hata Kyosho). 4,000 g of hard tablet oil, 400 g of hard coconut oil, 100 g of glyceryl monostearate (-KKOR MG S -B: Nikko Chemical) and 100 g of polyethylene glycol monostearate (40EO) (Nikkor MYS-40: Nikko Chemical) in ethanol Using a solution dissolved in 600 mL and 200 g of torque, a waterproof layer was applied to the uncoated tablets with a coating machine (Driacoater DRC-650, Norec) to produce 120 mg of protected locking tablets per tablet.

<Example 7>

 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.

<Example 8>

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. Using 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.

 <Example 9>

 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.

 [0048] <Comparative Example 5>

 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. Was dried with a coating machine (Drycoater DRC-650, Norec) while spraying the sugar coating liquid, to obtain 170 mg sugar coated tablets per tablet. The time spent on the coating work was one hour.

 [0049] <Comparative Example 6>

 Using 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) was used to obtain 200 mg sugar-coated tablets per tablet by the conventional sugar-coating method in which the sugar-coating liquid was sprayed, steamed and dried separately. The time spent on the coating work was 3.5 hours.

 [0050] <Production example 4>

3300 g of sodium norproate, 165 g of light anhydrous caustic acid and 303.6 g of ethyl cellulose are put into a high-speed stirring granulator (VG-25: Baurec) and granulated by adding ethanol. A product was prepared. This was dried with a fluidized bed dryer (FLO-5B: Freund Sangyo), and then dried with a granulator (Power Mill, Showa Chemical Machinery).

 2442 g of calcium stearate was mixed with 3426 g of the obtained sized product, and 230 mg of uncoated tablets per tablet were produced using this with a rotary type tableting machine (HP-AP18-SS: Hata Kyosho). Liquid obtained by dissolving and dispersing 60 g of ethyl cellulose, 30 g of methacrylic acid copolymer L (Eudragi tLlOO: Higuchi Shokai), 22.5 g of triethyl citrate and 22.5 g of light anhydrous caustic acid in 1365 g of ethanol. 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.

<Example 10>

 686 g of controlled release tablet obtained in Production Example 4, 93 g of granulated sugar, 3 g of talc, 51 g of precipitated calcium carbonate, 30% dispersion of ethyl acrylate and methyl methacrylate copolymer (Eudragit NE30D: Higuchi Shokai) and purification Using a suspended sugar coating solution consisting of 135.6 g of water, spray the sugar coating solution with a coating machine (NOI COATER HCT-30N, Freund Corporation) and dry it, 295 mg per tablet (of which sugar coating layer) The mass was 50 mg). The time spent on the coating work was 40 minutes.

<Example 11>

 686 g of controlled release tablet obtained in Production Example 4, 186 g of granulated sugar, 6 g of talc, 102 g of precipitated calcium carbonate, 30% dispersion of ethyl acrylate and methyl methacrylate copolymer (Eudragit NE30D: Higuchi Shokai) 20. lg and Using a sugar coating liquid that consists of 270.9 g of purified water, spray the sugar coating liquid with a coating machine (NOI COATER HCT-30N, Freund Sangyo) and dry it. 345 mg per tablet (of which the mass of the sugar coating layer) (LOOmg) sustained-release sugar-coated tablets were obtained. The time spent on the coating work was 75 minutes.

<Comparative Example 7>

686 g of controlled-release tablets obtained in Production Example 4 were mixed with 288.6 g of granulated sugar, 81.3 g of talc, 122.7 g of precipitated canoresic carbonate, 9.6 g of gum arabic, 4.5 g of gelatin, polyoxyethylene (1 05) Conventional spraying, steaming and drying of sugar coating liquid separately using a small sugar coating machine (manufactured by Kikusui Seisakusho) using a suspended sugar coating liquid consisting of 3.3 g of polyoxypropylene (5) glycol and 180 g of purified water By using the sugar coating method, 415 mg of underlay tablets were obtained per tablet. The time spent for this coating operation was 300 minutes. In addition, 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. Finally, using 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.

 [0054] From the above results, 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. In addition, the weight of the sugar-coated layer in sugar-coated tablets can be reduced to about one-half to one-fourth.

 [0055] <Evaluation of hygroscopicity>

 Ten tablets of the sugar-coated tablets obtained in Examples 1 to 9 and Comparative Examples 1 to 6 were measured at 25 ° C-84.3% for 1 hour, 2 hours, 3 hours and 24 hours. Then, the amount of moisture absorption was measured by comparing with the mass at the start, and the moisture absorption rate (%) was calculated. In addition, 40 sugar-coated tablets obtained in Examples 10 to 11 and Comparative Example 7 were used. C—Measure the mass after standing at 75% for 3 hours, 1 曰, 2 曰, 3 曰, 7 曰, 10 曰, 14 曰, 21 days, 28 days and 30 days, as above The moisture absorption rate (%) was calculated. The results are shown in Figs.

 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

[0056] From FIG. 1, 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.

[0057] From FIG. 2, 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. In addition, the sugar-coated preparation of Comparative Example 4 increased the moisture absorption rate to about 0.5% when allowed to stand for 24 hours.

[0058] From Fig. 3, 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.

 [0059] From Fig. 4, 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. In contrast, 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.

 [0060] As described above, when the sugar-coating liquid of the present invention is 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.

 [0061] <Evaluation of physical properties>

 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.

 [0062] [Table 1] Table 1

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. On the other hand, 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.

 [0064] [Table 2] Table 2

 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

[0065] The sugar-coated preparations of Examples 4 to 6 had sufficient hardness and excellent disintegration properties. On the other hand, 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.

 [0066] [Table 3] Table 3

 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

[0067] The sugar-coated preparations of Examples 7 to 9 had sufficient hardness and excellent disintegration properties. On the other hand, the sugar-coated preparations of Comparative Examples 5 and 6 were insufficient in hardness or disintegration.

 [0068] From the above, it was found that the sugar-coated preparation of the present invention has sufficient hardness and excellent disintegration properties.

 [0069] <Odor evaluation>

The odor of the sugar-coated tablets obtained in Examples 4 to 9 and Comparative Examples 3 to 6 was evaluated. About the generation of odor when the obtained preparation is stored in a transparent glass bottle and sealed at 60 ° C for 3 days, 1 week, and 2 weeks. 0: No unpleasant odor derived from the drug is felt. The evaluation was made on a four-point scale: 1: feel almost no unpleasant odor derived from drugs, 2: feel unpleasant odor derived from drugs, and 3: feel strongly unpleasant odor derived from drugs. The evaluation was performed by five people and the average value was calculated. The results are shown in Tables 4-5. [0070] [Table 4] Table 4

 Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Immediately after production 0 0 0 0 0

3 days later 0 0 0 1. 2 0

1 week later 0 ◦ 0 2.6 6 0

2 weeks later 0 0 0 3. 0 0

[0071] The sugar-coated preparations of Examples 4 to 6 and Comparative Example 4 had an unpleasant feeling of unpleasant odor derived from oxoamidin even after a storage period of 2 weeks. On the other hand, the sugar-coated preparation of Comparative Example 3 strongly felt an unpleasant odor derived from oxoamidin. In particular, it was found that the unpleasant odor became stronger as the storage was prolonged.

 [0072] [Table 5] Table 5

 Example 7 Example 8 Example 9 Comparative Example 5 Comparative Example 6 Immediately after production

 3 days later

 One week later

 2 weeks later

[0073] The sugar-coated preparations of Examples 7 to 9 and Comparative Example 6 were strong enough to hardly feel an unpleasant odor derived from MMSC even after a storage period of 2 weeks. On the other hand, the sugar-coated preparation of Comparative Example 5 felt an unpleasant odor due to MMSC after 3 days and a strong unpleasant odor after 1 week.

 [0074] From the above, it was found that the sugar-coated preparations of the present invention were superior in deodorizing properties compared to conventional sugar-coated preparations.

 [0075] <Evaluation of moisture value immediately after production>

 The sugar-coated tablets of Examples 7 to 9 and Comparative Examples 5 to 6 immediately after production were pulverized, weighed about 5 g, measured with a gas pressure moisture meter for 10 minutes using calcium hydride as a reaction reagent, and water content (%) Was calculated. The results are shown in Table 6.

[0076] [Table 6] Table 6

 Example 7 Example 8 Example 9 Comparative example 5 Comparative example 6 Moisture value (%) 1.6 5 1.5 5 5 1.6 2 1.5 5 6 2.4 8

[0077] The water content (%) of the sugar-coated preparations of Examples 7 to 9 and Comparative Example 5 were lower than those of the sugar-coated preparation of Comparative Example 6. Therefore, it was found that the moisture value in the tablet can be lowered by using the continuous coating method as compared with the conventional coating method.

 [0078] <Dissolution test>

 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.

 [0079] FIG. 5 shows that the sugar-coated preparation of the present invention is also excellent in sustained release properties. As described above, the sugar-coating liquid of the present invention is also useful for making a sugar-coating preparation of a drug that requires sustained release.

 [0080] As described above, 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.

 That is, according to the production method of the present invention, 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.

 Industrial applicability

[0081] 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.

Claims

The scope of the claims

 [1] A sugar-coating solution containing sugar, ethyl acrylate 'methyl methacrylate copolymer and solvent, and the concentration power of ethyl acrylate' methyl methacrylate copolymer is 0.0 against the total solid content.

Sugar-coating liquid that is 1-10% by weight.

[2] A sugar-coating preparation having a core material containing a drug and a sugar-coating layer covering the core material, wherein at least one of the sugar-coating layers is sugar and ethyl acrylate / methyl methacrylate copolymer 0.

A sugar-coating preparation, comprising 01 to 10% by weight.

[3] The sugar-coated preparation according to claim 2, further comprising a controlled release layer.

[4] The sugar-coated preparation according to claim 2 or 3, wherein the drug is a drug having an unpleasant odor !, a drug unstable to water, or a drug generating whisker.

[5] A method for producing a sugar-coating preparation, wherein the spraying step and the drying step of the sugar-coating liquid according to claim 1 are performed simultaneously.