Film coating composition, solid preparation, and method for producing the solid preparation

Abstract

To provide a composition for film coating that exhibits a sufficient deodorizing effect, causes no clogging of a spray nozzle during a coating step, and prevents roughening of tablet surfaces due to adhesion between tablets.SOLUTION: A composition for film coating comprises at least a nonionic water-soluble cellulose ether with viscosity of 2.0-50.0 mPa s in a 2 mass% aqueous solution at 20°C, pullulan and a solvent. A mass ratio of the nonionic water-soluble cellulose ether to pullulan is 80:20 to 55:45.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a film coating composition that masks the characteristic drug-derived odor emitted from tablets and the like, a solid preparation coated with the film coating composition, and a method for producing the solid preparation. [Background technology]

[0002] Film coating and sugar coating are widely used in oral solid preparations for purposes such as masking the unpleasant taste of drugs, blocking oxygen, preventing moisture, or improving the aesthetic appearance of the product. On the other hand, drugs may have an odor due to the active ingredient itself, impurities, or decomposition products.

[0003] In particular, technologies aimed at masking the odor of active ingredients, blocking oxygen, and preventing moisture include sugar coating and a film coating composition containing polyvinyl alcohol and 100% by mass or more of talc relative to the polyvinyl alcohol, which reduces adhesion and provides good film coating properties, can sufficiently block the odor of active ingredients, and has excellent oxygen blocking effects (Patent Document 1). Also, Patent Document 2 lists a film coating composition containing pullulan and a surfactant as a film coating composition for deodorizing solid preparations containing odorous drugs. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2006-188490 [Patent Document 2] Japanese Patent Application Laid-Open No. 2002-12541 Summary of the Invention [Problem to be solved by the invention]

[0005] However, sugar coating has problems such as the long process time required for sugar coating, increased manufacturing costs, large dosage forms that are difficult to ingest, 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, film coating compositions containing large amounts of inorganic substances, as described in Patent Document 1, do not form continuous coatings, resulting in poor coating strength and poor deodorizing properties. Furthermore, when the method described in Patent Document 2 is used, adhesion is reduced to some extent but not completely, and the coated tablet surface is not smooth.

[0006] The present invention has been made in view of the above circumstances, and aims to provide a film coating composition that exhibits sufficient deodorizing effect, does not cause clogging of spray nozzles in the coating process, and does not roughen the tablet surfaces due to adhesion between tablets, a solid preparation coated with the 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 film coating composition comprising a nonionic water-soluble cellulose ether, pullulan, and a solvent, and containing at least the nonionic water-soluble cellulose ether and pullulan in a predetermined ratio, and have completed the present invention.

[0008] According to the present invention, there are provided the following film coating composition, solid preparation, and method for producing the solid preparation. [1] A film coating composition comprising at least a nonionic water-soluble cellulose ether having a viscosity of 2.0 to 50.0 mPa·s in a 2% by weight aqueous solution at 20°C, pullulan, and a solvent, wherein the mass ratio of the nonionic water-soluble cellulose ether to pullulan is 80:20 to 55:45. [2] The film coating composition according to [1], wherein the total content of sugar alcohols and sugars is 30 parts by mass or less per 100 parts by mass of the total mass of the nonionic water-soluble cellulose ether and pullulan. [3] The film coating composition according to [1] or [2], wherein the nonionic water-soluble cellulose ether is selected from the group consisting of alkyl cellulose, hydroxyalkyl cellulose, and hydroxyalkyl alkyl cellulose. [4] The film coating composition according to any one of [1] to [3], wherein the solvent is selected from the group consisting of water and alcohols having 1 to 3 carbon atoms. [5] A solid preparation comprising at least a core containing at least an active ingredient and a coating obtained by coating the core with the film coating composition according to any one of [1] to [4]. [6] A method for producing a solid preparation, comprising at least a step of coating a core containing at least an active ingredient with the film coating composition according to any one of [1] to [4] to form a coating, and a step of drying to remove the solvent. [Effects of the Invention]

[0009] According to the present invention, there are provided a solid preparation suitable for oral administration, which has excellent deodorizing properties and improved adhesiveness, and has good film-coating properties, a method for producing the same, and a film-coating composition used in producing the solid preparation. DETAILED DESCRIPTION OF THE INVENTION

[0010] 1. Film coating composition First, we will describe a film coating composition that contains at least a nonionic water-soluble cellulose ether having a viscosity of 2.0 to 50.0 mPa·s in a 2% by mass aqueous solution at 20°C, pullulan, and a solvent, and in which the mass ratio of the nonionic water-soluble cellulose ether to pullulan is 80:20 to 55:45.

[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. Examples of alkyl cellulose include methyl cellulose (hereinafter also referred to as "MC"). The methoxy group content in methyl cellulose is preferably 26.0 to 33.0 mass%, more preferably 27.5 to 31.5 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.

[0012] 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.

[0013] 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.

[0014] As the nonionic water-soluble cellulose ether, from the viewpoint of providing a good coating layer (film), HPMC having 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%, or methylcellulose having a methoxy group content of preferably 26.0 to 33.0 mass%, is preferred.

[0015] The viscosity of a 2% by weight aqueous solution of the nonionic water-soluble cellulose ether at 20°C is 2.0 to 50.0 mPa·s, preferably 2.0 to 25.0 mPa·s, and more preferably 5.0 to 7.0 mPa·s. If the viscosity is less than 2.0 mPa·s, the degree of polymerization of the nonionic water-soluble cellulose ether will be extremely low, potentially resulting in a coating layer (film) that is unable to maintain its strength. On the other hand, if the viscosity exceeds 50.0 mPa·s, the concentration of the nonionic water-soluble cellulose ether in the film coating composition must be kept low, and the coating process will take a long time, preventing efficient production. The viscosity of a 2% by weight aqueous solution of the nonionic 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.

[0016] 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.

[0017] Pullulan is a type of polysaccharide composed solely of glucose, and is a water-soluble polymeric polysaccharide whose structural unit is maltotriose, which is made up of three glucose molecules linked together via α-1,4 bonds, and whose maltotriose units are linked via α-1,6 bonds.

[0018] The pullulan used in the present invention is not particularly limited in terms of average molecular weight or molecular weight distribution, and commercially available powdered pullulan can be used.

[0019] The mass ratio of nonionic water-soluble cellulose ether to pullulan in the film coating composition is 80:20 to 55:45, preferably 80:20 to 60:40. If the nonionic water-soluble cellulose ether exceeds 80, a sufficient deodorizing effect cannot be obtained. On the other hand, if the pullulan exceeds 45, clogging of the spray nozzle and adhesion of tablets occur during the coating process, resulting in a rough coating surface. On the other hand, if the nonionic water-soluble cellulose ether is less than 55, clogging of the spray nozzle and adhesion of tablets occur during the coating process, resulting in a rough coating surface. On the other hand, if the pullulan is less than 20, a sufficient deodorizing effect cannot be obtained.

[0020] Examples of the solvent include water or an alcohol having 1 to 3 carbon atoms, and may also be a mixed solvent of water and an alcohol having 1 to 3 carbon atoms. Examples of water include purified water. Examples of alcohol having 1 to 3 carbon atoms include ethanol, methanol, isopropyl alcohol, etc. Two or more types of solvents may be used in combination as necessary. From the viewpoints of productivity and operability during coating, water is preferred as the solvent.

[0021] The content of the solvent in the film coating composition is preferably 200 to 2,000 parts by mass, more preferably 900 to 930 parts by mass, per 100 parts by mass of the total mass of the nonionic water-soluble cellulose ether and pullulan, from the viewpoint of operability and workability during coating.

[0022] The film coating composition may contain additives, if necessary, such as sugars and sugar alcohols. Examples of sugars include monosaccharides or disaccharides such as sucrose, glucose, lactose, etc. In this specification, the term "sugars" does not include nonionic water-soluble cellulose ethers and pullulan. Examples of sugar alcohols include erythritol, xylitol, sorbitol, mannitol and maltitol. To overcome the problems of sugar-coated tablets, the total content of sugar alcohols and saccharides is preferably 30 parts by mass or less, more preferably 0 to 30 parts by mass, even more preferably 0 to 10 parts by mass, and particularly preferably 0 to 5 parts by mass, relative to 100 parts by mass of the total mass of nonionic water-soluble cellulose ether and pullulan. Addition of a small amount within this range has the advantage of further suppressing adhesion during coating and improving operability.

[0023] The film coating composition may further contain additives other than sugars and sugar alcohols, as needed, such as plasticizers, lubricants, glossing agents, surfactants, colorants, edible pigments, sweeteners, coating agents, and antifoaming agents.

[0024] 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.

[0025] 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.

[0026] 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. Examples of sweeteners include acesulfame potassium, saccharin, aspartame, and sucralose. Examples of coating agents include gum arabic, ethyl cellulose, hydroxypropyl cellulose, carboxyvinyl polymer, and carboxymethylethyl cellulose. Examples of antifoaming agents include glycerin fatty acid esters, dimethylpolysiloxane, silicon dioxide mixtures, and sucrose fatty acid esters.

[0027] The content of additives other than sugars and sugar alcohols in the film coating composition is preferably 30 parts by mass or less, more preferably 0 to 10 parts by mass, per 100 parts by mass of the total mass of the nonionic water-soluble cellulose ether and pullulan.

[0028] The film coating composition can be produced by mixing a nonionic water-soluble cellulose ether having a viscosity of 2.0 to 50.0 mPa·s in a 2% by mass aqueous solution at 20°C, pullulan, a solvent, and, if necessary, additives to obtain a film coating composition. There are no particular limitations on the method for mixing a nonionic water-soluble cellulose ether having a viscosity of 2.0 to 50.0 mPa·s in a 2% by mass aqueous solution at 20° C., pullulan, a solvent, and optional additives. For example, from the viewpoint of preventing the formation of "mamako" or gelation of the nonionic water-soluble cellulose ether, a method for producing a film coating composition may include at least the steps of mixing pullulan with a solvent to obtain a pullulan solution, and mixing the pullulan solution with the nonionic water-soluble cellulose ether.

[0029] In the step of obtaining a pullulan solution by mixing pullulan with a solvent, it is preferable to disperse pullulan in a solvent at 20 to 30° C. and then mix the solvent to dissolve the pullulan and obtain the pullulan solution. In addition, in the process of obtaining a film coating composition by mixing the pullulan solution with a nonionic water-soluble cellulose ether, it is preferable to disperse the nonionic water-soluble cellulose ether in the pullulan solution at a temperature of preferably 70 to 90°C, then cool the solution to a temperature of preferably 15 to 30°C, and mix the solution to dissolve the nonionic water-soluble cellulose ether, thereby obtaining a film coating composition.

[0030] A nonionic water-soluble cellulose ether having a viscosity of 2.0 to 50.0 mPa·s in a 2% by mass aqueous solution at 20°C, pullulan, a solvent, and optional additives can be mixed using a stirrer. The mixing time is not particularly limited as long as it is possible to dissolve the nonionic water-soluble cellulose ether having a viscosity of 2.0 to 50.0 mPa·s in a 2% by mass aqueous solution at 20°C and pullulan in the solvent.

[0031] 2. Solid dosage forms Next, solid preparations will be described. The solid preparation has at least a core containing at least an active ingredient and a coating formed by coating the core with the film 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.

[0032] 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.

[0033] Examples of central nervous system drugs include diazepam, idebenone, naproxen, piroxicam, indomethacin, sulindac, lorazepam, nitrazepam, phenytoin, acetaminophen, ethenzamide, ketoprofen, and chlordiazepoxide.

[0034] Examples of cardiovascular drugs include molsidomine, vinpocetine, propranolol, methyldopa, dipyridamole, furosemide, triamterene, nifedipine, atenolol, spironolactone, metoprolol, pindolol, captopril, isosorbide dinitrate, delapril hydrochloride, meclofenoxate hydrochloride, diltiazem hydrochloride, etilefrine hydrochloride, digitoxin, and alprenolol hydrochloride.

[0035] Examples of respiratory drugs include amlexanox, dextromethorphan, theophylline, pseudoephedrine, salbutamol, and guaifenesin.

[0036] 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.

[0037] Examples of antibiotics include talampicillin hydrochloride, bacampicillin hydrochloride, cefaclor, and erythromycin.

[0038] Examples of antitussives and expectorants include noscapine hydrochloride, carbetapentane citrate, isoaminyl citrate, and dimemorfan phosphate.

[0039] Examples of antihistamines include chlorpheniramine maleate, diphenhydramine hydrochloride, and promethazine hydrochloride.

[0040] Examples of the antipyretic, analgesic and anti-inflammatory agents include ibuprofen, diclofenac sodium, flufenamic acid, sulpyrine, aspirin and ketoprofen.

[0041] Examples of diuretics include caffeine.

[0042] Examples of autonomic agents include dihydrocodeine phosphate, dl-methylephedrine hydrochloride, atropine sulfate, acetylcholine chloride, and neostigmine.

[0043] Examples of antimalarial agents include quinine hydrochloride.

[0044] Examples of antidiarrheal agents include loperamide hydrochloride.

[0045] Examples of psychotropic drugs include chlorpromazine.

[0046] 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.

[0047] 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.

[0048] Examples of minerals include calcium, magnesium, manganese, zinc, iron, copper, selenium, chromium, sulfur, and iodine.

[0049] Examples of carotenoids include β-carotene, α-carotene, lutein, cryptoxanthin, zeaxanthin, lycopene, astaxanthin, and multi-carotene.

[0050] 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.

[0051] Examples of plant extracts include extracts of 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.

[0052] 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.

[0053] 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.

[0054] 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.

[0055] Examples of excipients include sugars such as sucrose, lactose, mannitol, and glucose, starch, crystalline cellulose, calcium phosphate, and calcium sulfate.

[0056] 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.).

[0057] 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.

[0058] Examples of lubricants (anti-agglomerating agents) include talc, magnesium stearate, calcium stearate, colloidal silica, stearic acid, waxes, hydrogenated oils, polyethylene glycols, and sodium benzoate.

[0059] Examples of the fluidizing agent include hydrous silicon dioxide, light anhydrous silicic acid, and titanium oxide.

[0060] 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.

[0061] Examples of solubilizing agents for pharmaceutical compounds include organic acids such as fumaric acid, succinic acid, malic acid, and adipic acid.

[0062] 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.

[0063] The shape (dosage form) of the core containing at least the active ingredient is not particularly limited, and examples include tablets, powders, granules, fine granules, pills, lozenges, capsules, etc., with tablets being particularly preferred. Examples of tablets include plain tablets, sugar-coated 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 film coating composition.

[0064] The amount of coating of the film coating composition applied to 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, and the properties of the drug and additives contained in the formulation. For example, when the core containing at least an active ingredient is in the form of a tablet (dosage form), the amount of solids in the film coating composition is preferably 0.5 to 15% by mass, and more preferably 5 to 10% by mass, based on 100 parts by mass of the core, from the viewpoint of uniformity of the amount of coating. The "amount of solids" of the film coating composition refers to the total amount of components of the film coating composition excluding the solvent, i.e., the total amount of nonionic water-soluble cellulose ether and pullulan, and includes the amount of optional additives, if any.

[0065] The thickness of the coating portion of the tablet is preferably 20 to 30 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).

[0066] 3. Manufacturing method of solid dosage forms The method for producing a solid preparation will be described. The solid preparation can be obtained by a production method including at least the steps of: coating a core containing at least an active ingredient with the film coating composition using a coating device to form a coating; and drying to remove the solvent. Examples of coating devices include pan coating devices, drum-type coating devices, fluidized bed coating devices, and agitation fluidized coating devices. Conventional coating devices can be used. Examples of spray devices attached to the coating device include air sprays, airless sprays, and three-fluid sprays. The coating method is not particularly limited, but for example, a method of applying a film coating composition to a core containing at least an active ingredient can be mentioned. In the step of removing the solvent by drying, known drying methods such as natural drying, drying using a tray dryer, and drying using a coating device of the through-air drying type can be used.

[0067] As described above, a solid dosage form can be produced that includes at least a core containing at least an active ingredient and a coating formed by coating with the film-coating composition. The coating formed by the film-coating composition contains at least a nonionic water-soluble cellulose ether and pullulan, whose viscosity in a 2% by weight aqueous solution at 20°C is 2.0 to 50.0 mPa·s, due to the removal of volatile components such as solvents, and the coating becomes a coating that contains at least the nonionic water-soluble cellulose ether and pullulan in a mass ratio of 80:20 to 55:45. The coating is impermeable to water molecules and has excellent water vapor barrier properties, resulting in excellent moisture resistance. This moisture resistance protects the core containing the active ingredient, which is susceptible to moisture, thereby reducing the generation of decomposition products. Furthermore, regardless of whether the active ingredient decomposes, odorous components emitted by the active ingredient can be trapped within the walls of the coating, resulting in deodorizing effects. A specific example of a solid preparation is a preparation comprising at least a core having the above-mentioned shape containing at least an active ingredient and a coating on the core. The film coating composition can also be used for capsule applications in addition to film coating applications. [Example]

[0068] 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.

[0069] Example 1 An aqueous solution of pullulan was prepared by dissolving 20 g of pullulan (manufactured by Hayashibara Co., Ltd., product name "Food Additive Pullulan") in 900 g of purified water by stirring at 25°C and 560 rpm for 15 minutes using a stirrer (Labo Stirrer (LT-400D), manufactured by Yamato Scientific Co., Ltd.). The prepared pullulan aqueous solution was stirred at 80°C and 560 rpm using a stirrer (Labo Stirrer (LT-400D), manufactured by Yamato Scientific Co., Ltd.) while 80 g of HPMC (viscosity of a 2% by mass aqueous solution at 20°C: 5.91 mPa s, methoxy group content: 28.8% by mass, hydroxypropoxy group content: 8.8% by mass) was added and dispersed in water by stirring at 80°C and 560 rpm for 3 minutes, and then the HPMC was dissolved by stirring at 20°C and 560 rpm for 15 minutes to produce a film coating composition. Using the obtained film coating composition, uncoated tablets having the following composition were used as cores, and under the coating conditions described below, the core tablets were coated with 10 parts by mass of solids (HPMC and pullulan) per 100 parts by mass of uncoated tablets.Then, without spraying the coating solution (film coating composition), the tablets were dried in the same apparatus for 30 minutes at an inlet air temperature of 50 to 60°C and a pan rotation speed of 18 rpm to produce film-coated tablets (solid formulations) with a coating formed on the uncoated tablets. <Composition of uncoated tablets> Aspirin: 50% by mass (Aspirin, manufactured by Yamamoto Chemical Industry Co., Ltd.) Lactose: 50% 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> Equipment: 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: 75~80℃ Exhaust temperature: 44~49℃ Intake air volume: 0.45m 3 / min Pan rotation speed: 18-24 rpm Spray rate: 5g / min Spray air pressure: 100kPa Nozzle diameter: 1.0 mm

[0070] <Evaluation criteria for occurrence of nozzle clogging during coating> Based on the following evaluation criteria, "A" was judged as "good," "◯" as "fair," and "×" as "poor." ◎: No nozzle blockage ○: Scale formation was observed, but no nozzle blockage occurred ×: Nozzle clogging occurred

[0071] <Evaluation criteria for surface roughness of coated tablets> Based on the following evaluation criteria, "◎" was judged as "good," "◯" as "fair," and "×" as "poor." No surface roughness or only partial roughness indicates that the adhesiveness has been improved. Surface roughness was confirmed visually. ◎: No surface roughness ○: Some surface roughness ×: Surface roughness present

[0072] <Evaluation of free acetic acid> Thirty film-coated tablets were placed in a vial designed for headspace samplers, sealed, and left to stand for 12 hours. After that, the amount of free acetic acid generated from the tablets was measured using a headspace sampler and gas chromatography under the following analytical conditions. If no free acetic acid was detected, it indicates that the product has a deodorizing effect. [Analysis conditions] <Autosampler (HS-20)> Sample line temperature: 150℃ Transfer line temperature: 150℃ Vial pressurization gas pressure: 50 kPa Injection time: 0.5 min Column name: SH-Stabilwax (liquid film thickness 0.5 μm, length 30 m, inner diameter 0.32 mm ID) Detector: FID1 Detector temperature: 250℃ Make-up gas: He Make-up flow rate: 24mL / min H2 flow rate: 30mL / min Air flow rate: 200mL / min Control mode: Linear velocity (40 cm / sec)

[0073] Examples 2 to 3 and Comparative Examples 1 to 4 Except for changing the composition of the film coating composition to that shown in Table 1, a coating composition was prepared in the same manner as in Example 1, and uncoated tablets were coated. The occurrence of nozzle clogging, surface roughness of the coated tablets, and free acetic acid were evaluated. In Example 3, MC (viscosity of a 2% by mass aqueous solution at 20°C: 4.04 mPa s, methoxy group content 29.4% by mass) was used as the nonionic water-soluble cellulose ether used in the film coating composition. The results are shown in Table 1.

[0074] As is clear from Table 1, the film-coated tablets of the present invention exhibited sufficient deodorizing effects, with no clogging of the spray nozzle during the coating process and no roughening of the tablet surfaces due to adhesion between tablets. Deodorizing was made possible by using a nonionic water-soluble cellulose ether and pullulan in a specified ratio. On the other hand, a certain concentration of free acetic acid was detected in the coated tablets of Comparative Example 1, and the deodorizing effect was insufficient. Furthermore, in Comparative Example 2, nozzle clogging occurred during coating, and the tablet surfaces became rough due to adhesion between tablets, and productivity was also poor.

[0075] [Table 1]

Claims

1. The composition comprises at least a nonionic water-soluble cellulose ether having a viscosity of 2.0 to 50.0 mPa s in a 2% by mass aqueous solution at 20°C, pullulan, and a solvent, wherein the mass ratio of the nonionic water-soluble cellulose ether to pullulan is 80:20 to 55:45, The content of sugar alcohol or sugar is more than 0 and 30 parts by mass or less per 100 parts by mass of the total mass of the nonionic water-soluble cellulose ether and pullulan. Film coating compositions.

2. 2. The film coating composition of claim 1, wherein the nonionic water-soluble cellulose ether is selected from the group consisting of alkyl celluloses, hydroxyalkyl celluloses, and hydroxyalkyl alkyl celluloses.

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

4. A solid preparation comprising at least a core containing at least an active ingredient and a coating obtained by coating the core with the film coating composition according to claim 1 or 2.

5. 3. A method for producing a solid preparation, comprising at least a step of coating a core containing at least an active ingredient with the film coating composition according to claim 1 to form a coating, and a step of drying to remove the solvent.

Images