JP2024039317A - Composition for film coating, solid preparation, and method for producing solid preparation - Google Patents

Abstract

The present invention provides a film coating composition that exhibits a sufficient deodorizing effect, does not cause clogging of spray nozzles in the coating process, and does not cause roughening of tablet surfaces due to adhesion of tablets to each other. [Solution] The present invention includes at least a nonionic water-soluble cellulose ether, pullulan, and a solvent whose viscosity of a 2% by mass aqueous solution at 20° C. is 2.0 to 50.0 mPa·s, the nonionic water-soluble cellulose ether and pullulan A film coating composition having a mass ratio of 80:20 to 55:45. [Selection diagram] None

Description

The present invention relates to a film coating composition for masking the characteristic drug-derived odor generated from tablets, etc., a solid preparation coated with the same, and a method for producing the solid preparation.

Film coating and sugar coating are widely used in oral solid preparations for purposes such as masking unpleasant taste of drugs, blocking oxygen, moisture proofing, and improving the aesthetic appearance of the product.
On the other hand, drugs may have odors due to their active ingredients themselves, impurities, and decomposition products.

In particular, techniques aimed at concealing odors derived from active ingredients, blocking oxygen, and moisture-proofing include, for example, sugar coating, polyvinyl alcohol, and talc containing 100% by mass or more based on the polyvinyl alcohol. A film coating composition (Patent Document 1) is known that can reduce tackiness and obtain good film coating properties, can sufficiently block the odor of the active ingredient, and has an excellent oxygen shielding effect. Further, Patent Document 2 cites a film coating composition containing pullulan and a surfactant as a film coating composition for deodorizing a solid preparation containing a drug having an odor.

Japanese Patent Application Publication No. 2006-188490 Japanese Patent Application Publication No. 2002-12541

However, sugar coating requires a long time for the sugar coating process, which increases manufacturing costs, makes the formulation so large that it is difficult to take, and the protein, which is the main component of gelatin used for coating, denatures and becomes unstable. There is a problem that there is a lack of
On the other hand, as mentioned in Patent Document 1, film coating compositions containing a large amount of inorganic substances do not form a continuous film, have poor film strength, and have poor odor resistance. Furthermore, when the method mentioned in Patent Document 2 is used, the tackiness is reduced to some extent, but not completely, and the coated tablet surface does not become smooth.

The present invention has been made in view of the above circumstances, and provides a film coating composition that exhibits sufficient deodorizing effects, does not cause clogging of spray nozzles during the coating process, and does not cause roughening of the tablet surface due to adhesion of tablets to each other. The object of the present invention is to provide a coated solid preparation and a method for producing the solid preparation.

As a result of extensive research to solve the above problems, the present inventors have discovered that the present invention contains nonionic water-soluble cellulose ether, pullulan, and a solvent, and that the nonionic water-soluble cellulose ether and pullulan are mixed in a predetermined ratio. The present invention was completed based on the discovery that the above object can be achieved by a film coating composition containing at least the following.

According to the present invention, the following film coating composition, solid preparation, and method for producing the solid preparation are provided.
[1] At least contains a nonionic water-soluble cellulose ether, pullulan, and a solvent whose viscosity in a 2% by mass aqueous solution at 20°C is 2.0 to 50.0 mPa·s, and the nonionic water-soluble cellulose ether and pullulan A film coating composition having a mass ratio of 80:20 to 55:45.
[2] The film coating composition according to [1], wherein the total content of sugar alcohol and saccharide is 30 parts by mass or less based on 100 parts by 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 portion containing at least an active ingredient, and a coating portion in which the core portion is coated with the film coating composition according to any one of [1] to [4].
[6] A step of coating a core portion containing at least an active ingredient with the film coating composition according to any one of [1] to [4] to form a coated portion, and drying to remove the solvent. A method for producing a solid dosage form, comprising at least the steps of:

According to the present invention, there is provided a solid preparation suitable for oral administration that has excellent deodorization properties, improved adhesion, and good film coating properties, a method for producing the same, and a film coating composition used for producing the solid preparation. can.

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

Nonionic water-soluble cellulose ether is a nonionic polymer obtained by etherifying some of the hydroxyl groups of cellulose. Examples of nonionic water-soluble cellulose ethers include alkylcellulose, hydroxyalkylcellulose, hydroxyalkylalkylcellulose, and the like.
Examples of the alkyl cellulose include methyl cellulose (hereinafter also referred to as "MC"). The content of methoxy groups in methylcellulose is preferably 26.0 to 33.0% by mass, more preferably 27.5 to 31.5% by mass. The content of methoxy groups in methylcellulose can be measured according to the analytical method for methylcellulose in the 18th edition of the Japanese Pharmacopoeia.

Examples of hydroxyalkylcellulose include hydroxypropylcellulose. The content of hydroxypropoxy groups in hydroxypropylcellulose is preferably 53.4 to 80.5% by mass, more preferably 60.0 to 70.0% by mass. The content of hydroxypropoxy groups in hydroxypropylcellulose can be measured according to the analytical method for hydroxypropylcellulose in the 18th edition of the Japanese Pharmacopoeia.

Examples of the hydroxyalkylalkylcellulose include hydroxypropylmethylcellulose (also known as "hypromellose", hereinafter also referred to as "HPMC"), and the like. The content of methoxy groups in HPMC is preferably 16.5 to 30.0% by mass, more preferably 28.0 to 30.0% by mass from the viewpoint of providing a good coating layer (film, film). It is. Further, the content of hydroxypropoxy groups in HPMC is preferably 4.0 to 32.0% by mass, more preferably 7.0 to 12.0% by mass, from the viewpoint of providing a good coating layer (film, film). It is 0% by mass. The content of hydroxypropoxy groups and methoxy groups in HPMC can be measured by the quantitative method described in the "hypromellose" section of the 18th edition of the Japanese Pharmacopoeia.

From the viewpoint of providing a good coating layer (film, film), the nonionic water-soluble cellulose ether preferably has a methoxy group content of 16.5 to 30.0% by mass, and a hydroxypropoxy group content. HPMC having a content of preferably 4.0 to 32.0% by mass and methylcellulose having a methoxy group content of preferably 26.0 to 33.0% by mass are preferred.

The viscosity of a 2% by mass aqueous solution of nonionic water-soluble cellulose ether at 20°C is 2.0 to 50.0 mPa·s, preferably 2.0 to 25.0 mPa·s, more preferably 5.0 to 7.0 mPa·s. It is 0 mPa·s. If it is less than 2.0 mPa·s, the degree of polymerization of the nonionic water-soluble cellulose ether will be extremely reduced, so there is a possibility that the strength of the coating layer (film, film) cannot be maintained. On the other hand, if it exceeds 50.0 mPa・s, the concentration of nonionic water-soluble cellulose ether in the film coating composition must be kept low, and the coating operation takes a long time, making efficient production difficult. Can not. The viscosity of a 2% by mass aqueous solution of nonionic water-soluble cellulose ether at 20°C was determined using an Ubbelohde viscometer according to the capillary viscometer method of the viscosity measurement method of the general test method described in the 18th edition of the Japanese Pharmacopoeia. can be measured.

Two or more types of nonionic water-soluble cellulose ethers may be used in combination, if necessary. Moreover, commercially available nonionic water-soluble cellulose ethers can be used.

Pullulan is a type of polysaccharide consisting only of glucose, and its constituent unit is maltotriose, in which three molecules of glucose are linked through α-1,4 bonds, and the maltotriose is linked through α-1,6 bonds. It is a water-soluble polymeric polysaccharide with

There are no particular limitations on the average molecular weight or molecular weight distribution of the pullulan used in the present invention, and commercially available powdered pullulan can be used.

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

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 the alcohol having 1 to 3 carbon atoms include ethanol, methanol, isopropyl alcohol, and the like. Two or more types of solvents may be used in combination as necessary. As the solvent, water is preferred from the viewpoint of productivity and operability during coating.

Moreover, a commercially available solvent can be used. From the viewpoint of operability and workability during coating, the content of the solvent in the film coating composition is preferably 200 to 2000 parts by mass based on 100 parts by mass of the total mass of nonionic water-soluble cellulose ether and pullulan. , more preferably 900 to 930 parts by mass.

The film coating composition may contain additives, if necessary. Examples of additives include sugars and sugar alcohols.
Examples of sugars include monosaccharides or disaccharides such as sucrose, glucose, and lactose. In addition, in this specification, "saccharide" does not include nonionic water-soluble cellulose ether and pullulan.
Examples of sugar alcohols include erythritol, xylitol, sorbitol, mannitol and maltitol.
In order to improve the above-mentioned problems of sugar-coated tablets, the total content of sugar alcohols and saccharides is preferably 30 parts by mass or less, more preferably 0 parts by mass, based on 100 parts by mass of nonionic water-soluble cellulose ether and pullulan. ~30 parts by weight, more preferably 0 to 10 parts by weight, particularly preferably 0 to 5 parts by weight. Addition of a small amount within the above range has the advantage of further suppressing adhesion during coating and improving operability.

Furthermore, the film coating composition may further contain additives other than sugars and sugar alcohols, if necessary. Examples of additives other than sugars and sugar alcohols include plasticizers, lubricants, brighteners, surfactants, colorants, edible pigments, sweeteners, coating agents, antifoaming agents, and the like.

Examples of plasticizers include glycerin, polyethylene glycol, propylene glycol, triethyl citrate, and the like.
Examples of lubricants include talc, magnesium stearate, calcium stearate, colloidal silica, stearic acid, and the like.
Examples of brightening agents include carnauba wax, shellac, beeswax, hydrogenated oils, magnesium stearate, and the like.

Examples of surfactants include polysorbate 80, polysorbate 60, sucrose fatty acid ester, macrogol 400, sodium lauryl sulfate, polyoxyl stearate 40, and polyoxyethylene hydrogenated castor oil 60.
Examples of colorants include yellow iron oxide, iron sesquioxide (red), orange essence, brown iron oxide, caramel, light silicic anhydride, 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 pigment, carotenoid pigment, flavonoid pigment, and quinone pigment. etc.

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 Examples include 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 the coating agent include gum arabic, ethylcellulose, hydroxypropylcellulose, carboxyvinyl polymer, and carboxymethylethylcellulose.
Examples of antifoaming agents include glycerin fatty acid esters, dimethylpolysiloxanes, silicon dioxide mixtures, sucrose fatty acid esters, and the like.

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 100 parts by mass, based on 100 parts by mass of the nonionic water-soluble cellulose ether and pullulan. It is 10 parts by mass.

The film coating composition is prepared by mixing nonionic water-soluble cellulose ether, pullulan, and a solvent whose viscosity in a 2% by mass aqueous solution at 20°C is 2.0 to 50.0 mPa·s, and optionally additives. By this, it can be manufactured by the process of obtaining a film coating composition.
There are no particular restrictions on the method of mixing the nonionic water-soluble cellulose ether, pullulan, and the solvent, whose viscosity in a 2% by mass aqueous solution at 20° C. is 2.0 to 50.0 mPa·s, and optional additives. For example, from the viewpoint of preventing the formation of "mamako" and gelation of nonionic water-soluble cellulose ether, the step of obtaining a film coating composition includes a step of obtaining a pullulan solution by mixing pullulan and a solvent; A method for producing a film coating composition includes at least a step of mixing the pullulan solution and a nonionic water-soluble cellulose ether.

In the step of obtaining a pullulan solution by mixing pullulan and a solvent, it is preferable to disperse pullulan in a solvent at 20 to 30° C. and then mix to dissolve the pullulan and obtain a pullulan solution.
In addition, in the step of obtaining a film coating composition by mixing the pullulan solution and nonionic water-soluble cellulose ether, nonionic water-soluble cellulose ether is preferably dispersed in the pullulan solution at 70 to 90°C. Thereafter, the nonionic water-soluble cellulose ether is preferably dissolved by cooling to preferably 15 to 30° C. and mixing to obtain a film coating composition.

A stirrer is used to mix the nonionic water-soluble cellulose ether whose viscosity in a 2% by mass aqueous solution at 20°C is 2.0 to 50.0 mPa·s, pullulan, a solvent, and additives as necessary. It can be done using The mixing time is not particularly limited as long as the nonionic water-soluble cellulose ether whose viscosity of a 2% by mass aqueous solution at 20° C. is 2.0 to 50.0 mPa·s and pullulan can be dissolved in the solvent.

2. Solid Preparation Next, solid preparations will be explained.
The solid preparation has at least a core portion containing at least an active ingredient, and a coating portion in which the core portion is coated with the film coating composition.
The active ingredient is not particularly limited as long as it is an orally administrable active ingredient, but it is used in drugs used in pharmaceuticals, and health foods such as foods with nutritional function claims, foods for specified health uses, and foods with functional claims. Examples include active ingredients. Alternatively, the core may be a capsule preparation filled with a filler containing at least an active ingredient.

Examples of drugs used in pharmaceuticals include central nervous system drugs, circulatory system drugs, respiratory drugs, digestive system drugs, antibiotics, antitussive and expectorant agents, antihistamines, antipyretic, analgesic, and antiinflammatory agents, diuretics, and antipyretic agents. Neuroactive drugs, antimalarial drugs, anti-lagogues, psychotropic drugs, vitamins and their derivatives, etc. can be mentioned.

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

Examples of cardiovascular drugs include molsidomine, vinpocetine, propranolol, methyldopa, dipyridamole, furosemide, triamterene, nifedibine, atenolol, spironolactone, metoprolol, pindolol, captopril, isosorbitate nitrate, delapril hydrochloride, meclofenoxate hydrochloride, diltiazem hydrochloride, Examples include etilefrine hydrochloride, digitoxin, and alprenolol hydrochloride.

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

Examples of gastrointestinal drugs include 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 drugs with antiulcer effects such as benzimidazole, cimetidine, ranitidine, pirenzepine hydrochloride, pancreatin, bisacodyl, and 5-aminosalicylic acid, etc. .

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

Examples of antitussive and expectorant agents include noscapine hydrochloride, carbetapentane citrate, isoaminyl citrate, and dimemorphan phosphate.

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

Examples of antipyretic, analgesic, and antiinflammatory agents include ibuprofen, diclofenac sodium, flufenamic acid, sulpirin, aspirin, and ketoprofen.

Examples of diuretics include caffeine and the like.

Examples of autonomic nerve agents include dihydrocodeine phosphate, dl-methylephedrine hydrochloride, atropine sulfate, acetylcholine chloride, neostigmine, and the like.

Examples of antimalarials include quinine hydrochloride and the like.

Examples of anti-lagogues include loperamide hydrochloride and the like.

Examples of psychotropic agents include chlorpromazine and the like.

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.

Examples of active ingredients used in health foods include the aforementioned vitamins and their derivatives, minerals, carotenoids, amino acids and their derivatives, plant extracts, and health food materials.

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

Examples of carotenoids include β-carotene, α-carotene, lutein, cryptoxanthin, zeaxanthin, lycopene, astaxanthin, multicarotene, and the like.

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, histidine, and the like.
Examples of neutral amino acids include linear aliphatic amino acids such as alanine and glycine, branched aliphatic amino acids such as valine, leucine and isoleucine, hydroxy amino acids such as serine and threonine, and sulfur-containing amino acids such as cysteine and methionine. Examples include amino acids, 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, ara Examples include nylglutamine, carnitine, and γ-aminobutyric acid.

Examples of plant extracts include aloe, propolis, agaricus, ginseng, ginkgo biloba, turmeric, curcumin, germinated brown rice, shiitake mycelium, sweet tea, sweet tea, meshimakobu, sesame, garlic, maca, cordyceps sinensis, chamomile, and capsicum. Examples include extracts.

Examples of health food ingredients include royal jelly, dietary fiber, protein, bifidobacteria, lactic acid bacteria, chitosan, yeast, glucosamine, lecithin, polyphenols, animal cartilage, soft-shelled turtle, lactoferrin, freshwater clam, eicosapentaenoic acid, germanium, enzymes, creatine, Examples include carnitine, citric acid, raspberry ketone, coenzyme Q10, methylsulfonylmethane, and phospholipid-bound soybean peptide.

The amount of active ingredient to be used can be appropriately determined depending on the type of formulation. Two or more types of active ingredients may be used in combination as necessary. Furthermore, commercially available active ingredients can be used.

The core portion containing at least the active ingredient contains one or more selected from excipients, binders, disintegrants, lubricants (anti-aggregation agents), flow agents, colorants, solubilizing agents for pharmaceutical compounds, etc. Additives may also be added.

Examples of excipients include sugars such as white sugar, lactose, mannitol, and glucose, starch, crystalline cellulose, calcium phosphate, and calcium sulfate.

Examples of binders include polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyvinylpyrrolidone, glucose, sucrose, lactose, maltose, dextrin, sorbitol, mannitol, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, macrogol ( Examples include macrogol 4000, macrogol 6000, macrogol 20000, etc.), gum arabic, gelatin, agar, and starch (cornstarch, etc.).

Examples of disintegrants include low-substituted hydroxypropylcellulose, carmellose or its salts, croscarmellose sodium, sodium carboxymethyl starch, crospolyvinylpyrrolidone, crystalline cellulose, and crystalline cellulose/carmellose sodium.

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

Examples of the fluidizing agent include hydrated silicon dioxide, light anhydrous silicic acid, and titanium oxide.

Examples of colorants include yellow iron sesquioxide, iron sesquioxide, food blue No. 1, food blue No. 2, food yellow No. 4, food yellow No. 5, food green No. 3, food red No. 2, and food red No. 3. , Food Red No. 102, Food Red No. 104, Food Red No. 105, Food Red No. 106, and the like.

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

The amount of the additive to be used can be determined as appropriate depending on the type of formulation and the like. Two or more types of additives may be used in combination as necessary. Moreover, commercially available additives can be used.

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, troches, and capsules, among which tablets are particularly preferred. preferable.
Examples of tablets include plain tablets, sugar-coated tablets, gelatin-coated tablets, film-coated tablets (including multilayer film-coated tablets), enteric-coated tablets, and dry-coated tablets (compressed tablets).
Furthermore, if necessary, the core portion containing at least the active ingredient may be subjected to undercoating treatment using a coating base such as hydroxypropyl methyl cellulose before being coated with the film coating composition.

The amount of film coating composition coated on the surface of the core containing at least the active ingredient depends on the type, shape, size, surface condition of the preparation, properties of the drug and additives contained in the preparation, etc. It can be determined as appropriate. For example, when the shape (dosage form) of the core containing at least the active ingredient is a tablet, the solid content of the film coating composition is The amount is preferably 0.5-15% by weight, more preferably 5-10% by weight. The "solid content" of the film coating composition is the total amount of the components of the film coating composition excluding the solvent, that is, the total amount of nonionic water-soluble cellulose ether and pullulan. When containing additives according to the above, the amount includes the content of the additives.

Further, the thickness of the coating portion of the tablet is preferably 20 to 30 μm from the viewpoint of forming a uniform continuous film (layer). The thickness of the coating in the tablet can be measured using a digital microscope VHX-2000 (Keyence Corporation).

3. Method for manufacturing solid preparations The method for manufacturing solid preparations will be explained.
The solid preparation includes at least the steps of: coating a core containing at least the active ingredient with the film coating composition using a coating device to form a coating; and drying to remove the solvent. obtained by the method. Examples of coating equipment include pan coating equipment, drum type coating equipment, fluidized bed coating equipment, and agitated fluidized coating equipment. As the coating device, conventionally known devices can be used. Further, examples of spray devices 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 includes, for example, a method of applying a film coating composition to the core portion containing at least the active ingredient.
In the step of drying to remove the solvent, known drying methods include natural drying, a drying method using a tray dryer, and a drying method using a ventilation drying type coating device.

As described above, a solid preparation comprising at least a core portion containing at least an active ingredient and a coating portion formed by coating the above-described film coating composition can be produced. Since volatile components such as solvents are removed from the coating formed by the above-mentioned film coating composition, the coating is nonionic and has a viscosity of 2.0 to 50.0 mPa·s as a 2% by mass aqueous solution at 20°C. The coating portion contains at least water-soluble cellulose ether and pullulan, and the mass ratio of the nonionic water-soluble cellulose ether to the pullulan is 80:20 to 55:45. The coating portion is difficult to pass water molecules and has excellent water vapor barrier properties, so it has excellent moisture resistance. This moisture-proof property protects the core containing active ingredients that are susceptible to moisture, making it difficult for decomposition products to occur, and odor components emitted from active ingredients regardless of whether they are decomposed or not. can also be trapped by the wall of the coating, leading to an odor-proofing effect.
Specific examples of solid preparations include, for example, preparations that include at least a core portion having the above-mentioned shape and containing an active ingredient, and a coating portion on the core portion. Furthermore, the film coating composition can be used not only for film coating purposes but also for capsule purposes.

EXAMPLES Below, the present invention will be specifically explained with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples.

Example 1
20 g of Pullulan (manufactured by Hayashibara Co., Ltd., trade name ``Food Additive Pullulan'') was stirred in 900 g of purified water at 25°C and 560 rpm for 15 minutes using a stirrer (Labo Stara (LT-400D), manufactured by Yamato Scientific Co., Ltd.). An aqueous solution of pullulan was prepared by dissolving it.
While stirring the prepared pullulan aqueous solution at 80°C and 560 rpm using a stirrer (Labo Stirra (LT-400D), manufactured by Yamato Scientific Co., Ltd.), HPMC (viscosity of 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 at 20°C and 560 rpm. The HPMC was dissolved by stirring for 15 minutes to prepare a film coating composition.
Using the obtained composition for film coating, using the core of an uncoated tablet having the following composition, under the following coating conditions, the solid content (HPMC and pullulan) was 10 parts by mass per 100 parts by mass of the uncoated tablet. After coating until the coating solution (film coating composition) was coated, drying was performed in the same device for 30 minutes without spraying the coating solution (film coating composition) at a supply air temperature of 50 to 60 ° C. and a pan rotation speed of 18 rpm. A film-coated tablet (solid preparation) in which a coating portion was formed on a plain tablet was manufactured.
<Composition of uncoated tablet>
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 Kagaku Sangyo Co., Ltd.)
Tablet shape: diameter 8.0 mm, radius of curvature 12.0 mm, mass 200 mg/tablet

<Coating conditions>
Equipment: Ventilated pan coater (HICOATER FZ LABO, inner diameter of coating pan 30 cm, manufactured by Freund Sangyo Co., Ltd.)
Amount of uncoated tablets: 1kg
Supply air temperature: 75-80℃
Exhaust temperature: 44-49℃
Intake air amount: 0.45m ³ /min
Pan rotation speed: 18-24 rpm
Spray speed: 5g/min
Spray air pressure: 100kPa
Nozzle diameter: 1.0mm

<Evaluation criteria for occurrence of nozzle blockage during coating>
Below, based on each evaluation criterion, "◎" was determined to be "good,""○" was determined to be "fair," and "x" was determined to be "poor."
◎: No nozzle blockage occurred. ○: Scale formation was observed, but nozzle blockage did not occur. ×: Nozzle blockage occurred.

<Evaluation criteria for surface roughness of coated tablets>
Below, based on each evaluation criterion, "◎" was determined to be "good,""○" was determined to be "fair," and "x" was determined to be "poor." If there is no surface roughness or only some surface roughness, it indicates that the tackiness has been improved. Surface roughness was visually confirmed.
◎: No surface roughness ○: Some surface roughness ×: Surface roughness

<Evaluation of free acetic acid>
30 film-coated tablets were placed in a vial exclusively for the headspace sampler, and the vial was sealed and allowed to stand for 12 hours. Then, free acetic acid generated from the tablets was measured using a headspace sampler and gas chromatography under the following analysis conditions. . If free acetic acid is not detected, it indicates that there is a deodorizing effect.
[Analysis conditions]
≪Auto sampler (HS-20)≫
Sample line temperature: 150℃
Transfer line temperature: 150℃
Gas pressurization for vial pressurization: 50kPa
Injection time: 0.5min

Column name: SH-Stabilwax (liquid phase film thickness 0.5 μm, length 30 m, inner diameter 0.32 mm ID)
Detector: FID1
Detector temperature: 250℃

Make-up gas: He
Makeup flow rate: 24mL/min
_H2 flow rate: 30mL/min
Air flow rate: 200mL/min
Control mode: linear velocity (40cm/sec)

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

As is clear from Table 1, the film-coated tablets of the present invention exhibited sufficient deodorizing effects, did not cause blockage of the spray nozzle during the coating process, and did not cause roughening of the tablet surface due to adhesion of tablets to each other. Odor control has become possible by using nonionic water-soluble cellulose ether and pullulan in a predetermined ratio.
On the other hand, in the coated tablet of Comparative Example 1, a certain concentration of free acetic acid was detected, and the deodorizing effect was not sufficient. Furthermore, in Comparative Example 2, nozzle clogging occurred during coating, and the tablet surface was roughened due to adhesion of tablets to each other, resulting in poor productivity.

Claims (6)

A 2% by mass aqueous solution at 20° C. contains at least a nonionic water-soluble cellulose ether, pullulan, and a solvent with a viscosity of 2.0 to 50.0 mPa s, and the mass ratio of the nonionic water-soluble cellulose ether to pullulan. A composition for film coating, wherein the ratio is from 80:20 to 55:45. 2. The film coating composition according to claim 1, wherein the content of sugar alcohol and saccharide is 30 parts by mass or less based on 100 parts by mass of the nonionic water-soluble cellulose ether and pullulan. The film coating composition according to claim 1 or 2, wherein the nonionic water-soluble cellulose ether is selected from the group consisting of alkylcellulose, hydroxyalkylcellulose, and hydroxyalkylalkylcellulose. The film coating composition according to claim 1 or 2, wherein the solvent is selected from the group consisting of water and alcohols having 1 to 3 carbon atoms. A solid preparation comprising at least a core portion containing at least an active ingredient, and a coating portion in which the core portion is coated with the film coating composition according to claim 1 or 2. A solid preparation comprising at least the steps of: coating a core containing at least an active ingredient with the film coating composition according to claim 1 or 2 to form a coating; and drying to remove the solvent. Production method.