Coating composition, solid preparation, and method for producing the solid preparation

Abstract

To provide a composition for coating that minimizes drug release in the oral cavity, reducing unpleasant taste during ingestion, while ensuring efficient drug release in the gastrointestinal tract once the drug has passed through the oral cavity.SOLUTION: A composition for coating contains at least a nonionic water-soluble cellulose ether, tannin and a solvent. The mass ratio between the nonionic water-soluble cellulose ether and the tannin ranges from 98.0:2.0 to 83.3:16.7.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a coating composition that can mask the unpleasant taste of a drug in the oral cavity and then rapidly release the drug, a solid preparation coated with the coating composition, and a method for producing the solid preparation. [Background technology]

[0002] Film coating and sugar coating are widely used in oral solid dosage forms for purposes such as masking the unpleasant taste of drugs, blocking light to maintain drug stability, color coating to improve the distinguishability of oral solid dosage forms, preventing wear and tear during transportation of oral solid dosage forms, improving the aesthetic appearance of the product, and imparting other specific properties.

[0003] In particular, as a technique for masking the bitter taste of oral solid preparations, for example, sugar coating and film coating that does not disintegrate in the oral cavity by utilizing the gelling properties of methylcellulose have been proposed (Patent Document 1). Furthermore, a technique has been proposed in which a tablet containing an effervescent component and a drug is coated with a composition containing multiple water-soluble bases in order to impart floating properties in the stomach (Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 60-13719 [Patent Document 2] Japanese Patent Application Publication No. 2018-199630 Summary of the Invention [Problem to be solved by the invention]

[0005] However, sugar coating has problems such as the long sugar coating process, increased manufacturing costs, large dosage forms that are difficult to administer, and a lack of stability due to denaturation of the protein that is the main component of the gelatin used for coating. On the other hand, as mentioned in Patent Document 1, when methylcellulose is used as a coating agent, methylcellulose undergoes thermal gelation at 37°C and becomes insoluble in water, so that the drug can be taken without feeling sticky or slimy, but there is a concern that the thermal gelation may cause delays in drug dissolution.Patent Document 2 states that if the catechin content in the coating layer exceeds a certain amount, the coating will crack.In this case, it is possible that the drug will be unintentionally dissolved, making it difficult to control drug dissolution.

[0006] The present invention has been made in view of the above circumstances, and aims to provide a coating composition that suppresses the dissolution of a drug in the oral cavity, thereby suppressing the unpleasant taste of the drug when taken, and that exhibits excellent drug dissolution properties in the digestive tract after passing through the oral cavity, a solid preparation coated with the coating composition, and a method for producing the solid preparation. [Means for solving the problem]

[0007] As a result of extensive research to solve the above problems, the inventors have found that the above object can be achieved by a coating composition containing a nonionic water-soluble cellulose ether, a tannin, and a solvent, and containing at least the nonionic water-soluble cellulose ether and the tannin in a predetermined ratio. They have completed the present invention, which is a coating technology that requires a lower coating amount than bitterness masking using conventional film coating technology and is also highly productive.

[0008] According to the present invention, there are provided the following coating composition, solid preparation, and method for producing a solid preparation. [1] A coating composition comprising at least a nonionic water-soluble cellulose ether, a tannin, and a solvent, wherein the mass ratio of the nonionic water-soluble cellulose ether to the tannin is 98.0:2.0 to 83.3:16.7. [2] The coating composition according to [1], wherein the viscosity of a 2% by mass aqueous solution of the nonionic water-soluble cellulose ether at 20°C is 2.0 to 50.0 mPa·s. [3] The coating composition according to [1] or [2], wherein the nonionic water-soluble cellulose ether is at least one water-soluble cellulose ether selected from the group consisting of alkyl cellulose, hydroxyalkyl cellulose, and hydroxyalkyl alkyl cellulose. [4] The coating composition according to any one of [1] to [3], wherein the tannin is at least one type of tannin selected from the group consisting of hydrolyzable tannins and condensed tannins. [5] The coating composition according to any one of [1] to [4], wherein the solvent is selected from the group consisting of water and alcohols having 1 to 3 carbon atoms. [6] A solid preparation comprising at least a core containing at least an active ingredient and a coating formed by coating the core with the coating composition according to any one of [1] to [5]. [7] A method for producing a solid preparation, comprising at least a step of applying the coating composition according to any one of [1] to [5] to a core containing at least an active ingredient, and a step of drying to remove the solvent. [8] The method according to [7], wherein in the coating step, the solid content of the coating composition is 0.1 to 10 mass % relative to the core containing at least the active ingredient. [Effects of the Invention]

[0009] According to the present invention, by coating a solid preparation containing a drug that exhibits an unpleasant taste with a coating composition containing at least a nonionic water-soluble cellulose ether, a tannin, and a solvent, it is possible to provide a solid preparation suitable for oral administration that can suppress drug dissolution in the oral cavity, suppress the unpleasant taste of the drug, and exhibit excellent drug dissolution properties in the digestive tract after passing through the oral cavity. DETAILED DESCRIPTION OF THE INVENTION

[0010] 1. Coating composition First, a coating composition containing at least a nonionic water-soluble cellulose ether and a tannin in a mass ratio of 98.0:2.0 to 83.3:16.7, and a solvent, will be described.

[0011] Nonionic water-soluble cellulose ethers are nonionic polymers in which some of the hydroxyl groups of cellulose have been etherified. Examples of nonionic water-soluble cellulose ethers include alkyl celluloses, hydroxyalkyl celluloses, and hydroxyalkyl alkyl celluloses.

[0012] Examples of alkyl cellulose include methyl cellulose. The methoxy group content in methyl cellulose is preferably 26.0 to 33.0% by mass, more preferably 27.5 to 31.5% by mass. The methoxy group content in methyl cellulose can be measured in accordance with the analytical method for methyl cellulose in the 18th Edition of the Japanese Pharmacopoeia.

[0013] Examples of hydroxyalkyl cellulose include hydroxypropyl cellulose. The hydroxypropyl cellulose preferably has a hydroxypropoxy group content of 53.4 to 80.5% by mass, more preferably 60.0 to 70.0% by mass. The hydroxypropoxy group content of hydroxypropyl cellulose can be measured in accordance with the analytical method for hydroxypropyl cellulose in the 18th Edition of the Japanese Pharmacopoeia.

[0014] Examples of hydroxyalkyl alkyl cellulose include hydroxypropyl methylcellulose (also known as "hypromellose," hereinafter also referred to as "HPMC"). The methoxy group content in HPMC is preferably 16.5 to 30.0 mass% and more preferably 28.0 to 30.0 mass% from the viewpoint of providing a good coating layer (film). The hydroxypropoxy group content in HPMC is preferably 4.0 to 32.0 mass% and more preferably 7.0 to 12.0 mass% from the viewpoint of providing a good coating layer (film). The hydroxypropoxy group and methoxy group contents in HPMC can be measured by the quantitative method described in the section on "hypromellose" in the 18th Edition of the Japanese Pharmacopoeia.

[0015] As the nonionic water-soluble cellulose ether, from the viewpoint of providing a good coating layer (film), preferred are hydroxyalkyl alkyl celluloses such as HPMC, which have a methoxy group content of preferably 16.5 to 30.0 mass% and a hydroxypropoxy group content of preferably 4.0 to 32.0 mass%, and alkyl celluloses, which have a methoxy group content of preferably 26.0 to 33.0 mass%, respectively.

[0016] The viscosity of a 2% by weight aqueous solution of the nonionic water-soluble cellulose ether at 20°C is preferably 2.0 to 50.0 mPa·s, more preferably 2.0 to 25.0 mPa·s, and even more preferably 5.0 to 7.0 mPa·s. A viscosity of 2.0 mPa·s or higher is preferred because the nonionic water-soluble cellulose ether provides a coating layer (film) with adequate strength, while a viscosity of 50.0 mPa·s or lower is preferred from the standpoint of productivity, since the concentration of the nonionic water-soluble cellulose ether in the coating composition is appropriate for efficient coating. The viscosity of a 2% by weight aqueous solution of the water-soluble cellulose ether at 20°C can be measured using an Ubbelohde viscometer according to the capillary viscometer method in the viscosity measurement method of the general test methods described in the 18th Edition of the Japanese Pharmacopoeia.

[0017] Two or more types of nonionic water-soluble cellulose ethers may be used in combination as needed. Commercially available nonionic water-soluble cellulose ethers can also be used.

[0018] Tannins are a type of polyphenol, a general term for aromatic compounds with a complex structure, molecular weight of about 600 to 2000, containing numerous phenolic hydroxyl groups, and are widely distributed in the plant kingdom. They are broadly divided into hydrolyzable tannins, which are formed by ester bonds between one or more gallic acid units and sugars, and condensed tannins, which are derivatives of flavanols. Hydrolyzable tannins include tannic acid, and condensed tannins include persimmon tannin and theaflavin.

[0019] The mass ratio of nonionic water-soluble cellulose ether to tannin in the coating composition is 98.0:2.0 to 83.3:16.7, preferably 98.0:2.0 to 91.7:8.3. If the nonionic water-soluble cellulose ether exceeds 98.0, the unpleasant taste of the drug cannot be suppressed. On the other hand, if the tannin exceeds 16.7, the coating film becomes insolubilized, resulting in a significant decrease in drug dissolution. On the other hand, if the nonionic water-soluble cellulose ether is less than 83.3, the coating film becomes insolubilized, resulting in a significant decrease in drug dissolution. On the other hand, if the tannin is less than 2.0, the water solubility of the coating film increases, and the unpleasant bitter taste of the drug cannot be suppressed.

[0020] Examples of the solvent include water and lower alcohols having 1 to 3 carbon atoms, and may also be mixed solvents of water and lower alcohols having 1 to 3 carbon atoms. Examples of water include purified water. Examples of lower alcohols having 1 to 3 carbon atoms include ethanol, methanol, isopropyl alcohol, etc. As the solvent, a mixed solvent of water and lower alcohols having 1 to 3 carbon atoms is preferred from the viewpoints of productivity and operability during coating.

[0021] Two or more types of solvents may be used in combination as necessary. Commercially available solvents can be used. From the viewpoint of operability and workability during coating, the content of the solvent in the coating composition is preferably 200 to 2,000 parts by mass, more preferably 1,300 to 1,900 parts by mass, per 100 parts by mass of the total mass of the nonionic water-soluble cellulose ether and tannin.

[0022] The coating composition may contain additives as needed, such as plasticizers, lubricants, glossing agents, surfactants, colorants, edible pigments, sweeteners, coating agents, and antifoaming agents. Examples of plasticizers include glycerin, polyethylene glycol, propylene glycol, and triethyl citrate. Examples of lubricants include talc, magnesium stearate, calcium stearate, colloidal silica, and stearic acid. Examples of glossing agents include carnauba wax, shellac, beeswax, hydrogenated oil, and magnesium stearate.

[0023] Examples of surfactants include polysorbate 80, polysorbate 60, sucrose fatty acid ester, macrogol 400, sodium lauryl sulfate, polyoxyl 40 stearate, polyoxyethylene hydrogenated castor oil 60, and the like. Examples of coloring agents include yellow iron oxide, ferric oxide (red), orange essence, brown iron oxide, caramel, light anhydrous silicic acid, Food Blue No. 5, Food Yellow No. 4, Food Yellow No. 4 Aluminum Lake, Food Yellow No. 5, Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Blue No. 2, talc, sodium fluorescein, green tea powder, vitamin C, food lake dye, carotenoid dye, flavonoid dye, and quinone dye.

[0024] Examples of edible pigments include carbon black, Food Red No. 2 Aluminum Lake, Food Red No. 3 Aluminum Lake, Food Red No. 40 Aluminum Lake, Food Yellow No. 4 Aluminum Lake, Food Yellow No. 5 Aluminum Lake, Food Blue No. 1 Aluminum Lake, Food Blue No. 2 Aluminum Lake, iron sesquioxide, yellow iron sesquioxide, and black iron oxide. Sweeteners include acesulfame potassium, sucralose, palatinose, maltose, xylitol, etc. Examples of coating agents include gum arabic, ethyl cellulose, hydroxypropyl cellulose, carboxyvinyl polymer, and carboxymethylethyl cellulose. Antifoaming agents include glycerin fatty acid esters, dimethylpolysiloxane, silicon dioxide mixtures, sucrose fatty acid esters, and the like.

[0025] The content of the additive in the coating composition is not particularly limited, but is preferably 200 parts by mass or less, more preferably 0 to 100 parts by mass, per 100 parts by mass of the total mass of the nonionic water-soluble cellulose ether and tannin.

[0026] The coating composition can be produced by a process of mixing a nonionic water-soluble cellulose ether, a tannin, a solvent, and, if necessary, additives to obtain a coating composition. The method or order of mixing the nonionic water-soluble cellulose ether, tannin, solvent, and optional additives is not particularly limited. For example, from the viewpoint of preventing the formation of "mamako" or gelation of the nonionic water-soluble cellulose ether, a production method can be mentioned which includes at least the steps of mixing tannin and a solvent to obtain a tannin solution and mixing the tannin solution with the nonionic water-soluble cellulose ether as a step of obtaining a coating composition.

[0027] In the step of obtaining a tannin solution by mixing tannin with a solvent, it is preferable to obtain the tannin solution by dissolving the tannin in a lower alcohol, preferably one having 1 to 3 carbon atoms, and mixing the tannin therein. In the step of mixing the tannin solution with the nonionic water-soluble cellulose ether, it is preferable to disperse the nonionic water-soluble cellulose ether in a tannin solution dissolved in a lower alcohol having 1 to 3 carbon atoms, and then add water and mix to dissolve the nonionic water-soluble cellulose ether to obtain a coating composition.

[0028] The nonionic water-soluble cellulose ether, tannin, solvent, and optional additives can be mixed using a stirrer. The mixing time is not particularly limited as long as the nonionic water-soluble cellulose ether and tannin can be dissolved in the solvent.

[0029] 2. Solid dosage forms Next, solid preparations will be described. The solid preparation has a core containing at least an active ingredient and a coating formed by coating the core with the coating composition. The active ingredient is not particularly limited as long as it is an orally administrable active ingredient, and examples thereof include drugs used in pharmaceuticals and active ingredients used in health foods such as functional foods, foods for specified health uses, and foods with functional claims. The core may also be a capsule formulation filled with a filler containing at least the active ingredient.

[0030] Examples of drugs used in pharmaceuticals include central nervous system drugs, circulatory system drugs, respiratory system drugs, digestive system drugs, antibiotics, antitussives and expectorants, antihistamines, antipyretic analgesics and anti-inflammatory drugs, diuretics, autonomic nervous system acting drugs, antimalarials, antidiarrheals, psychotropic drugs, and vitamins and their derivatives.

[0031] Examples of central nervous system drugs include diazepam, idebenone, naproxen, piroxicam, indomethacin, sulindac, lorazepam, nitrazepam, phenytoin, acetaminophen, ethenzamide, ketoprofen, and chlordiazepoxide.

[0032] Examples of cardiovascular drugs include molsidomine, vinpocetine, propranolol, methyldopa, dipyridamole, furosemide, triamterene, nifedivine, atenolol, spironolactone, metoprolol, pindolol, captopril, isosorbide dinitrate, delapril hydrochloride, meclofenoxate hydrochloride, diltiazem hydrochloride, etilefrine hydrochloride, digitoxin, and alprenolol hydrochloride.

[0033] Examples of respiratory drugs include amlexanox, dextromethorphan, theophylline, pseudoephedrine, salbutamol, and guaifenesin.

[0034] Examples of gastrointestinal drugs include benzimidazole drugs with antiulcer activity such as 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylsulfinyl]benzimidazole and 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridyl)methylsulfinyl]benzimidazole, cimetidine, ranitidine, pirenzepine hydrochloride, pancreatin, bisacodyl, and 5-aminosalicylic acid.

[0035] Examples of antibiotics include talampicillin hydrochloride, bacampicillin hydrochloride, cefaclor, and erythromycin.

[0036] Examples of antitussives and expectorants include noscapine hydrochloride, carbetapentane citrate, isoaminyl citrate, and dimemorfan phosphate.

[0037] Examples of antihistamines include chlorpheniramine maleate, diphenhydramine hydrochloride, and promethazine hydrochloride.

[0038] Examples of the antipyretic, analgesic and anti-inflammatory agents include ibuprofen, diclofenac sodium, flufenamic acid, sulpyrine, aspirin and ketoprofen.

[0039] Examples of diuretics include caffeine.

[0040] Examples of autonomic agents include dihydrocodeine phosphate, dl-methylephedrine hydrochloride, atropine sulfate, acetylcholine chloride, and neostigmine.

[0041] Examples of antimalarial agents include quinine hydrochloride.

[0042] Examples of antidiarrheal agents include loperamide hydrochloride.

[0043] Examples of psychotropic drugs include chlorpromazine.

[0044] Examples of vitamins and derivatives thereof include vitamin A, vitamin B1, fursultiamine, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, and calcium pantothenate.

[0045] Examples of active ingredients used in health foods include the above-mentioned vitamins and derivatives thereof, minerals, carotenoids, amino acids and derivatives thereof, plant extracts, and health food ingredients.

[0046] Examples of minerals include calcium, magnesium, manganese, zinc, iron, copper, selenium, chromium, sulfur, and iodine.

[0047] Examples of carotenoids include β-carotene, α-carotene, lutein, cryptoxanthin, zeaxanthin, lycopene, astaxanthin, and multicarotene.

[0048] Examples of amino acids include acidic amino acids, basic amino acids, neutral amino acids, and acidic amino acid amides. Examples of acidic amino acids include aspartic acid and glutamic acid. Examples of basic amino acids include lysine, arginine, and histidine. Examples of neutral amino acids include straight-chain aliphatic amino acids such as alanine and glycine, branched aliphatic amino acids such as valine, leucine, and isoleucine, hydroxyamino acids such as serine and threonine, sulfur-containing amino acids such as cysteine ​​and methionine, aromatic amino acids such as phenylalanine and tyrosine, heterocyclic amino acids such as tryptophan, imino acids such as proline, and unnatural amino acids such as tranexamic acid. Examples of acidic amino acid amides include asparagine and glutamine. Examples of amino acid derivatives include acetylglutamine, acetylcysteine, carboxymethylcysteine, acetyltyrosine, acetylhydroxyproline, 5-hydroxyproline, glutathione, creatine, S-adenosylmethionine, glycylglycine, glycylglutamine, dopa, alanylglutamine, carnitine, and γ-aminobutyric acid.

[0049] Examples of plant extracts include aloe, propolis, agaricus, ginseng, ginkgo biloba, turmeric, curcumin, germinated brown rice, shiitake mushroom mycelium, sweet tea, sweet tea, Phellinus linteus, sesame, garlic, maca, cordyceps, chamomile, and chili pepper.

[0050] Examples of health food ingredients include royal jelly, dietary fiber, protein, bifidobacteria, lactic acid bacteria, chitosan, yeast, glucosamine, lecithin, polyphenols, animal and fish cartilage, soft-shelled turtle, lactoferrin, clams, eicosapentaenoic acid, germanium, enzymes, creatine, carnitine, citric acid, raspberry ketone, coenzyme Q10, methylsulfonylmethane, and phospholipid-bound soy peptides.

[0051] The amount of the active ingredient used can be determined appropriately depending on the type of preparation. Two or more active ingredients may be used in combination as needed. In addition, commercially available active ingredients can be used.

[0052] The core containing at least the active ingredient may contain one or more additives selected from excipients, binders, disintegrants, lubricants (anti-agglomerating agents), fluidizing agents, colorants, and solubilizing agents for pharmaceutical compounds.

[0053] Examples of excipients include sugars such as sucrose, lactose, mannitol, and glucose, starch, crystalline cellulose, calcium phosphate, and calcium sulfate.

[0054] Examples of binders include polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyvinylpyrrolidone, glucose, sucrose, lactose, maltose, dextrin, sorbitol, mannitol, hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, macrogols (e.g., macrogol 4000, macrogol 6000, macrogol 20000, etc.), gum arabic, gelatin, agar, and starch (corn starch, etc.).

[0055] Examples of disintegrants include low-substituted hydroxypropyl cellulose, carmellose or its salts, croscarmellose sodium, sodium carboxymethyl starch, croscarmellose polyvinylpyrrolidone, crystalline cellulose, and crystalline cellulose-carmellose sodium.

[0056] Examples of lubricants (anti-agglomerating agents) include talc, magnesium stearate, calcium stearate, colloidal silica, stearic acid, waxes, hydrogenated oils, polyethylene glycols, and sodium benzoate.

[0057] Examples of the fluidizing agent include hydrous silicon dioxide, light anhydrous silicic acid, and titanium oxide.

[0058] Examples of coloring agents include yellow ferric oxide, ferric oxide, Food Blue No. 1, Food Blue No. 2, Food Yellow No. 4, Food Yellow No. 5, Food Green No. 3, Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Red No. 104, Food Red No. 105, and Food Red No. 106.

[0059] Examples of solubilizing agents for pharmaceutical compounds include organic acids such as fumaric acid, succinic acid, malic acid, and adipic acid.

[0060] The amount of additives used can be determined appropriately depending on the type of formulation, etc. Two or more types of additives may be used in combination as needed. In addition, commercially available additives can be used.

[0061] The shape (dosage form) of the core containing at least the active ingredient is not particularly limited, and examples include oral solid preparations such as tablets, powders, granules, fine granules, pills, lozenges, and capsules, with tablets being particularly preferred. Examples of tablets include plain tablets, gelatin-coated tablets, film-coated tablets (including multi-layer film-coated tablets), enteric-coated tablets, and dry-coated tablets (compression-coated tablets). Furthermore, the core containing at least the active ingredient may be subjected to undercoating treatment using a coating base such as hydroxypropylmethylcellulose, if necessary, before being coated with the coating composition.

[0062] The amount of coating composition used to coat the surface of a core containing at least an active ingredient can be determined appropriately depending on the type, shape, size, and surface condition of the formulation, the properties of the drug and additives contained in the formulation, etc. For example, when the shape (dosage form) of the core containing at least the active ingredient is a tablet, the amount of solids in the coating composition is preferably 0.1 to 10% by mass, and more preferably 0.3 to 5% by mass, relative to the core containing at least the active ingredient, from the viewpoint of uniformity of the amount of coating.

[0063] The thickness of the coating portion of the tablet is preferably 5 to 10 μm from the viewpoint of forming a uniform continuous coating (layer). The thickness of the coating portion of the tablet can be measured using a digital microscope VHX-2000 (Keyence Corporation).

[0064] 3. Manufacturing method of solid dosage form The method for producing a solid preparation will be described. The solid preparation can be produced by coating a core containing at least an active ingredient with the coating composition using a conventionally known coating device. Examples of the coating device include a pan coating device, a drum-type coating device, a fluidized bed coating device, and an agitation fluidized coating device. Examples of the spray device attached to the coating device include an air spray, an airless spray, and a three-fluid spray. The coating method is not particularly limited, but for example, a method of applying a coating composition to a core containing at least an active ingredient can be mentioned. After application, the coating composition may be dried as needed. That is, one example of a method for producing a solid preparation includes at least the steps of applying the coating composition to a core containing at least an active ingredient and drying to remove the solvent. In the application step, the coating composition may be applied in an amount such that the solid content of the coating composition is, for example, preferably 0.1 to 10.0 mass %, more preferably 0.3 to 5 mass %, relative to the core containing at least the active ingredient. The "solid content" of the coating composition refers to the total amount of components of the coating composition excluding the solvent, i.e., the total amount of nonionic water-soluble cellulose ether and tannin, and also includes the content of optional additives, if any.

[0065] As described above, a solid preparation can be produced that includes at least a core containing at least an active ingredient and a coating formed from the coating composition. Examples of the preparation include tablets and capsules. The coating formed from the coating composition contains a nonionic water-soluble cellulose ether and tannin in a mass ratio of 98.0:2.0 to 83.3:16.7, since volatile components such as solvents have been removed. For example, a solid preparation can be produced which comprises at least a core containing at least an active ingredient and a coating on the surface of the core. The coating composition can also be used for capsule applications in addition to coating applications. [Example]

[0066] EXAMPLES The present invention will be specifically explained below with reference to examples and comparative examples, but the present invention is not limited to these examples.

[0067] Example 1 A tannic acid solution was prepared by dissolving tannic acid (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) in 74.4 g of ethanol to a concentration of 0.1% by weight using a stirrer (Labo Stirrer (LT-400D), manufactured by Yamato Scientific Co., Ltd.) at 25°C and 500 rpm for 5 minutes. While stirring the prepared tannic acid solution at 25°C and 500 rpm using a stirrer (Labo Stirrer (LT-400D), manufactured by Yamato Scientific Co., Ltd.), HPMC (viscosity of a 2% by weight aqueous solution at 20°C: 5.91 mPa·s, methoxy group content: 28.8% by weight, hydroxypropoxy group content: 8.8% by weight) was added to the tannic acid solution to a concentration of 5% by weight. This was dispersed by stirring at 25°C and 500 rpm for 3 minutes. Then, 18.6 g of water was added and the mixture was stirred at 25°C and 500 rpm for an additional 5 minutes to produce a coating composition. Using the obtained coating composition, uncoated tablets having the following composition were used as cores and coated under the following coating conditions until the solid content (HPMC and tannic acid) reached 0.5 parts by mass per 100 parts by mass of uncoated tablets. Subsequently, the uncoated tablets were dried in the same apparatus for 30 minutes without spraying the coating composition, with an inlet air temperature of 50-60°C and a pan rotation speed of 18 rpm, to form a coating layer on the uncoated tablets, thereby obtaining solid preparations (coated tablets). The composition and shape of the uncoated tablets, and the coating conditions were as follows: <Composition of uncoated tablets> Riboflavin: 2% by mass (riboflavin, manufactured by Kyowa Pharma Chemical Co., Ltd.) Lactose: 98% by mass (Pharmatose (registered trademark) 200M, manufactured by DFE Pharma) Magnesium stearate: 1% by mass (magnesium stearate, manufactured by Taihei Chemical Industry Co., Ltd.) Tablet shape: diameter 8.0 mm, radius of curvature 12.0 mm, weight 200 mg / tablet <Coating conditions> Apparatus: Ventilated pan coater (HICOATER FZ LABO, coating pan inner diameter 30 cm, manufactured by Freund Corporation) Amount of uncoated tablets: 1 kg Intake air temperature: 55℃ Exhaust temperature: 37~40℃ Intake air volume: 0.6 m 3 / min Pan rotation speed: 18 rpm Spray rate: 4.5 g / min Spray air pressure: 100 kPa Nozzle diameter: 1.0 mm

[0068] Examples 2 and 3 and Comparative Examples 1 and 2 Except for mainly changing the content of tannic acid and changing the composition of the coating composition to the composition shown in Table 1, coating compositions were prepared in the same manner as in Example 1, and uncoated tablets were coated.

[0069] The results are shown in Table 1.

[0070] Example 4 The same procedure as in Example 1 was repeated, except that the nonionic water-soluble cellulose ether used in the coating composition was changed to MC (viscosity of a 2% by mass aqueous solution at 20°C: 4.04 mPa·s, methoxy group content: 29.4% by mass).

[0071] <Evaluation of dissolution characteristics> The coated tablets obtained in Examples 1 to 4 and Comparative Examples 1 and 2 were evaluated for dissolution by the dissolution test described in the 18th Edition of the Japanese Pharmacopoeia (37°C, paddle method, 100 rpm, 900 mL of purified water as solvent). The drug dissolution rates in Examples 1 to 4 and Comparative Examples 1 and 2 are shown in Table 1. As is clear from Table 1, the coated tablets of the present invention suppress initial drug dissolution and then rapidly release the drug. The use of nonionic water-soluble cellulose ether and tannin made it possible to control the initial dissolution. The coated tablets of Comparative Example 1 required more than 6 hours for the drug to begin to dissolve. Furthermore, the coated tablets of Comparative Example 2 rapidly released the drug in the initial stage, and the initial dissolution suppression could not be controlled.

[0072] [Table 1]

Claims

1. A coating composition for solid preparations, comprising at least a nonionic water-soluble cellulose ether, a tannin, and a solvent, wherein the mass ratio of the nonionic water-soluble cellulose ether to the tannin is 98.0:2.0 to 83.3:16.

7.

2. 2. The coating composition for solid preparations according to claim 1, wherein the viscosity of a 2% by mass aqueous solution of the nonionic water-soluble cellulose ether at 20° C. is 2.0 to 50.0 mPa·s.

3. 3. The coating composition for solid preparations according to claim 1, wherein the nonionic water-soluble cellulose ether is at least one water-soluble cellulose ether selected from the group consisting of alkyl cellulose, hydroxyalkyl cellulose, and hydroxyalkyl alkyl cellulose.

4. 3. The coating composition for solid preparations according to claim 1, wherein the tannin is at least one tannin selected from the group consisting of hydrolyzable tannins and condensed tannins.

5. 3. The coating composition for solid preparations according to claim 1, wherein the solvent is selected from the group consisting of water and lower alcohols having 1 to 3 carbon atoms.

6. A solid preparation comprising at least a core containing at least an active ingredient and a coating formed by coating the core with the coating composition for solid preparations according to claim 1 or 2.

7. A method for producing a solid preparation, comprising at least a step of applying the coating composition for a solid preparation according to claim 1 or 2 to a core containing at least an active ingredient, and a step of drying to remove the solvent.

8. 8. The method according to claim 7, wherein in the coating step, the solid content of the coating composition for solid preparations is 0.1 to 10% by mass with respect to the core containing at least the active ingredient.

Images