Solid Dosage Forms

Abstract

This invention provides a technology to suppress discoloration when cetirizines and specific components are present together. [Solution] A solid preparation comprising the following components (A) to (C) in a first container. (A) At least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. (B) At least one selected from the group consisting of the following components (B1) and (B2) (B1) At least one selected from the group consisting of glycyrrhizic acid, its salts, and their hydrates. (B2) At least one selected from the group consisting of licorice and its extracts. (C) Desiccant

Description

Technical Field

[0001] The present invention relates to solid preparations.

Background Art

[0002] As technologies for improving the stability of solid preparations, there are those described in Patent Documents 1 and 2. Patent Document 1 (Japanese Unexamined Patent Application Publication No. 2011-116733) describes a pharmaceutical preparation containing loxoprofen or a salt thereof, codeines, and a desiccant in a container (Claim 1), and thereby, it is said that the interaction between loxoprofen or a salt thereof and codeines can be suppressed, and thus, a solid preparation containing loxoprofen or a salt thereof and codeines with excellent storage stability can be provided (Paragraph 0012).

[0003] Also, Patent Document 2 (Japanese Unexamined Patent Application Publication No. 2013-28595) describes that when cetirizine hydrochloride and tranexamic acid are mixed and stored, discoloration and changes in properties over time occur (Paragraph 0007). And it is said that by further blending a basic pharmaceutical additive and / or hydrated silicon dioxide with cetirizine hydrochloride and tranexamic acid, discoloration and changes in properties when cetirizine hydrochloride and tranexamic acid are blended can be prevented (Paragraph 0008).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] When the inventors investigated incorporating cetirizines into solid dosage forms, they newly discovered that solid dosage forms containing cetirizines along with certain other components undergo discoloration during storage.

[0006] Therefore, the present invention provides a technology for stably incorporating cetirizines and specific components into a solid dosage form. [Means for solving the problem]

[0007] In other words, embodiments of the present invention are as follows. [1] A solid preparation containing the following components (A) to (C) in the first container. (A) At least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. (B) At least one selected from the group consisting of the following components (B1) and (B2) (B1) At least one selected from the group consisting of glycyrrhizic acid, its salts, and their hydrates. (B2) At least one selected from the group consisting of licorice and its extracts. (C) Desiccant [2] The solid preparation comprises a solid composition containing the components (A) and (B), The solid preparation according to [1], wherein the component (C) is located outside the solid composition in the first container. [3] The solid preparation according to [2], wherein the dosage form of the solid composition is selected from the group consisting of tablets, orally disintegrating tablets, chewable tablets, powders, capsules, and granules. [4] The solid preparation according to [2] or [3], wherein the solid composition is a pharmaceutical composition. [5] The solid preparation according to any one of [2] to [4], wherein the solid composition is a drug for treating rhinitis. [6] The solid preparation according to any one of [2] to [5], wherein the solid composition is a cold medicine. [7] The amount of component (A) in the solid composition per day is 1 mg or more and 20 mg or less, The solid preparation according to any one of [2] to [6], wherein the content of the component (B) in the solid composition per daily dose is 1 mg or more and 300 mg or less. [8] The solid preparation according to any one of claims [2] to [7], wherein the mass ratio ((A) / ((A)+(B))) of the content of the component (A) to the total amount of the components (A) and (B) in the solid composition is 0.01 or more and 0.9 or less. [9] The solid preparation according to any one of [2] to [8], wherein the mass ratio ((A) / ((A)+(C))) of the content of the component (A) to the total amount of the components (A) and (C) in one of the first containers is 0.005 or more and 0.35 or less.

[10] The solid preparation according to any one of [2] to [9], wherein the first container is at least one container selected from the group consisting of a bottle, a can, a synthetic resin bottle, a PTP container, a SP container, a paper container, and a natural resin bottle.

[11] The color difference ΔE of the solid composition before and after storage, measured by the following method and obtained by the following formula (I) * is 20 or less, and the solid preparation according to any one of [2] to

[10] . (Method) The solid preparation is stored at 60 ° C for 1 month in a sealed state, and each sample before and after storage is measured with a spectrocolorimeter under the following conditions in accordance with JIS Z 8722, and the chromaticity coordinates defined in the CIE1976L * a * b * color system are obtained, and the color difference ΔE * is determined. ΔE * ={(L * 2 - L * {1} 2 +(a * 2 - a * {1} 2 +(b * 2 - b * {1} 2} 1 / 2 (I) (In the above formula (I), (L * {1}, a * {1}, b * {1}) and (L *2,a * 2,b * 2) The CIE1976L of the solid composition before storage and after storage at 60°C for one month. * a * b * These are chromaticity coordinates defined by a color system.

[12] A solid preparation containing the following components (A) and (B) in a second container, The following component (C) and A package containing the first container. (A) At least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. (B) At least one selected from the group consisting of glycyrrhizic acid, its salts and their hydrates. (C) Desiccant

[13] The packaging according to

[12] , wherein the first container is at least one selected from the group consisting of pillow containers and individual packaging boxes.

[14] A solid composition comprising the following components (A) to (C): (A) At least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. (B) At least one selected from the group consisting of glycyrrhizic acid, its salts and their hydrates. (C) Desiccant [Effects of the Invention]

[0008] According to the present invention, cetirizines and specific components can be stably blended into a solid dosage form. [Modes for carrying out the invention]

[0009] Embodiments of the present invention will be described below. In this embodiment, the composition may contain each component individually or in combination of two or more components. In this specification, the "~" symbol indicating a numerical range represents "greater than or equal to" and "less than or equal to," and includes both of the numbers at either end.

[0010] (Solid dosage form) In this embodiment, the solid dosage form contains the following components (A) to (C) in the first container. (A) At least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. (B) At least one selected from the group consisting of the following components (B1) and (B2) (B1) At least one selected from the group consisting of glycyrrhizic acid, its salts, and their hydrates. (B2) Licorice or its extract (C) Desiccant

[0011] In this embodiment, since the solid dosage form contains components (A) to (C) in the first container, the cetirizines of component (A) and component (B) can be stably blended into the solid dosage form. More specifically, this embodiment effectively suppresses discoloration when the first container is tightly sealed and stored at 60°C for, for example, two weeks or more, or for, for example, one month or more.

[0012] Furthermore, as described later in the Examples section (Table 4), the inventors' studies revealed that the combination of cetirizine and tranexamic acid may discolor when stored under open conditions, while significant discoloration may not occur under tightly sealed conditions. In contrast, the combination of components (A) and (B) discolors even under tightly sealed conditions, suggesting that a different phenomenon is occurring compared to the combination of cetirizine and tranexamic acid, and thus requiring a higher level of discoloration suppression. In this regard, in this embodiment, components (A) to (C) are contained in the first container, so the discoloration that occurs with the combination of components (A) and (B) can be effectively suppressed.

[0013] (Component (A)) Component (A) is at least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. An example of an optical isomer of cetirizine is levocetirizine (the R-enantiomer of cetirizine). Examples of salts include hydrochloride salts. Examples of salts of cetirizine and its optical isomers include cetirizine salts such as cetirizine dihydrochloride and levocetirizine salts such as levocetirizine hydrochloride. In order to more effectively obtain the physiological activity of component (A), component (A) preferably comprises at least one of levocetirizine and its salts.

[0014] The amount of component (A) in the solid dosage form per day is preferably 1 mg or more, more preferably 3 mg or more, and even more preferably 5 mg or more. This allows for the appropriate acquisition of the physiological activity effect of component (A) while keeping the intake of the solid dosage form low. Furthermore, the amount of component (A) in the solid dosage form per day is preferably 20 mg or less, more preferably 15 mg or less, and even more preferably 10 mg or less. This allows for safer administration.

[0015] (Component (B)) Component (B) is at least one selected from the group consisting of glycyrrhizic acid compounds, plants containing them, and their extracts, and specifically, at least one selected from the group consisting of the following components (B1) and (B2). (B1) At least one selected from the group consisting of glycyrrhizic acid, its salts, and their hydrates. (B2) At least one selected from the group consisting of licorice and its extracts.

[0016] (Component (B1) Component (B1) is at least one selected from the group consisting of glycyrrhizic acid, its salts, and their hydrates. Specifically, components (B1) include glycyrrhizic acid; sodium salts such as trisodium glycyrrhizinate and disodium glycyrrhizinate; potassium salts such as monopotassium glycyrrhizinate and dipotassium glycyrrhizinate; and ammonium salts such as monoammonium glycyrrhizinate and diammonium glycyrrhizinate; as well as hydrates thereof. Component (B1) preferably comprises at least one selected component consisting of dipotassium glycyrrhizinate and ammonium glycyrrhizinate. This makes it possible to more reliably obtain a discoloration-inhibiting effect.

[0017] The amount of component (B1) in the solid dosage form per day is preferably 1 mg or more, more preferably 3 mg or more, and even more preferably 20 mg or more, as glycyrrhizic acid. This allows for the effective use of component (B1) while keeping the amount of solid dosage form consumed low. Furthermore, the amount of component (B1) in the solid dosage form per day is preferably 300 mg or less, more preferably 250 mg or less, and even more preferably 200 mg or less, as glycyrrhizic acid. This allows for even safer administration.

[0018] (Component (B2)) Component (B2) is at least one selected from the group consisting of licorice and its extracts.

[0019] Glycyrrhiza is a perennial herbaceous plant belonging to the genus Glycyrrhiza in the legume family. Examples of licorice include Glychyrrhiza glabra, Glychyrrhiza inflata, Glychyrrhiza uralensis, Glychyrrhiza aspera, Glychyrrhiza eurycarpa, Glychyrrhiza pallidiflora, Glychyrrhiza yunnanensis, Glychyrrhiza lepidota, Glychyrrhiza echinata, and Glychyrrhiza acanthocarpa. The raw material or extract of licorice is preferably at least one selected from the group consisting of Glychyrrhiza glabra, Glychyrrhiza uralensis, and Glychyrrhiza inflata.

[0020] The parts of the licorice plant used are, for example, one or more parts selected from the group consisting of leaves, branches, bark, trunk, stem, fruit, seeds, flowers, roots, rhizomes, and mixtures thereof, preferably one or more parts selected from the group consisting of leaves, roots, and rhizomes. Commercially available licorice or licorice powder may be used as ingredient (B2).

[0021] Furthermore, when licorice extract is used as component (B2), the extraction method for obtaining the extract can be, for example, a method of extracting the raw material in a solvent. The raw material can be, for example, the parts mentioned above. The extraction solvent includes, for example, one or more selected from the group consisting of water; monohydric alcohols having 1 to 3 carbon atoms such as methyl alcohol and ethyl alcohol; liquid polyhydric alcohols such as propylene glycol and 1,3-butylene glycol; lower alkyl esters such as ethyl acetate; hydrocarbons such as benzene and hexane; and ethers such as ethyl ether, and preferably includes one or more solvents selected from the group consisting of water and monohydric alcohols having 1 to 3 carbon atoms. The extraction temperature may be room temperature (25°C). Alternatively, for example, the extraction may be performed by heating to below the boiling point of the solvent. After extraction, the extract may be filtered and purified, or it may be deodorized and decolorized, for example. The extract may also be diluted or concentrated as appropriate and dried. Alternatively, commercially available extracts such as licorice extract can be used.

[0022] The amount of component (B2) in the solid dosage form per day is preferably 50 mg or more, more preferably 100 mg or more, and even more preferably 200 mg or more, in terms of crude drug equivalent. This allows for the effective use of component (B1) while keeping the intake of the solid dosage form low. Furthermore, the content of component (B2) in the solid dosage form per day is preferably 5,000 mg or less, more preferably 2,000 mg or less, and even more preferably 1,200 mg.

[0023] When a solid preparation has a solid composition containing components (A) and (B2), the amount of component (B2) in the solid composition administered daily is preferably 1% by mass or more, more preferably 5% by mass or more, even more preferably 10% by mass, and preferably 70% by mass or less, more preferably 50% by mass or less, and even more preferably 30% by mass or less, relative to the total amount of the solid composition in terms of crude drug equivalent. This allows for more efficient acquisition of the efficacy of component (B2).

[0024] Furthermore, when the solid formulation has a solid composition containing components (A) and (B), and component (C) is in the first container and outside the solid composition, the content of component (A) in the solid composition per day is preferably 1 mg to 20 mg, and the content of component (B) in the solid composition per day is preferably 1 mg to 300 mg, thereby enabling a more stable discoloration suppression effect.

[0025] When a solid preparation has a solid composition containing components (A) and (B), and component (C) is in the first container and outside the solid composition, the mass ratio of the content of component (A) to the total amount of components (A) and (B) in the solid composition ((A) / ((A)+(B))) is preferably 0.01 or more, more preferably 0.02 or more, and even more preferably 0.05 or more. This makes it possible to obtain a discoloration suppression effect more reliably. Similarly, the above mass ratio ((A) / ((A)+(B))) is preferably 0.9 or less, more preferably 0.6 or less, and even more preferably 0.4 or less.

[0026] (Component (C)) Component (C) is a desiccant. Preferably, component (C) has the function of reducing moisture transfer to the solid composition by absorbing moisture itself and drying the inside of the container. Component (C) is, for example, at least one selected from the group consisting of a desiccant having at least one silica and silicate, such as silica gel, silica alumina gel (allophene), zeolite, and bentonite clay (montmorillonite); a desiccant having a calcium compound such as calcium chloride and quicklime; and a desiccant having a magnesium compound such as magnesium chloride and magnesium oxide. In terms of more reliably obtaining the discoloration-inhibiting effect of the solid composition, component (C) preferably contains silica gel, and more preferably silica gel. Furthermore, the properties of component (C) include tablet form, granular form, powder form, etc.

[0027] The type and properties of component (C) can be selected, for example, according to the form of the solid dosage form described later. For example, when the solid dosage form includes a solid composition containing components (A) to (C) (the third embodiment described later), component (C) can be selected from components and properties that can be incorporated into the solid composition.

[0028] The amount of component (C) in the solid dosage form per day is preferably 30 mg or more, more preferably 50 mg or more, and even more preferably 90 mg or more. This ensures a more reliable discoloration-inhibiting effect. Furthermore, the amount of component (C) in the solid dosage form per day is preferably 1200 mg or less, more preferably 700 mg or less, and even more preferably 400 mg or less. This allows for a more efficient suppression of discoloration.

[0029] When a solid preparation has a solid composition containing components (A) and (B), and component (C) is in a first container and outside the solid composition, the mass ratio of the content of component (A) to the total amount of components (A) and (C) in one first container ((A) / ((A)+(C))) is preferably 0.005 or more, more preferably 0.01 or more, and even more preferably 0.05 or more. This makes it possible to obtain a discoloration suppression effect more efficiently. Furthermore, the above mass ratio ((A) / ((A)+(C))) is preferably 0.35 or less, more preferably 0.3 or less, even more preferably 0.25 or less, and even more preferably 0.2 or less. This makes it possible to more reliably obtain the discoloration suppression effect.

[0030] The composition contained in the first container, for example, a solid composition containing components (A) and (B), may further contain components other than components (A) to (C). As other components included in the solid preparation, one or more other active ingredients selected from the group consisting of antipyretic analgesics, antitussives / expectorants, antihistamines, anti-inflammatory agents, anticholinergics, other vitamins, xanthine derivatives, and sedatives may be appropriately added within a range that does not impair the effects of the present invention. If there are any contraindications for combining these ingredients, they may be appropriately divided into granules or otherwise formulated.

[0031] Examples of antipyretic analgesics include one or more selected from the group consisting of loxoprofen, its salts and hydrates (such as loxoprofen sodium dihydrate), aspirin, aluminum aspirin, acetaminophen, ethenzamide, sazapyrine, salicylamide, lactylphenetidine, ibuprofen, isopropylantipyrine, pranophene, diclofenac sodium, mefenamic acid, indomethacin farnesil, acemetacin, etodolac, naproxen, meloxicam, celecoxib, sodium salicylate, and tiaramide hydrochloride.

[0032] Examples of cough suppressants and expectorants include codeine, codeine phosphate hydrate, dihydrocodeine, dihydrocodeine phosphate, dibnate sodium, dimemorphan phosphate, tipepidine citrate, tipepidine hibenzate, dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalein salt, alloclamide hydrochloride, cloperastine hydrochloride, cloperastine fendizoate, pentoxyverin cyanate, noscapine, and noscapine hydrochloride. This includes one or more selected from the group consisting of trimethoquinol hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, l-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, L-carbocysteine, ambroxol hydrochloride, bromhexine hydrochloride, and L-ethylcysteine ​​hydrochloride.

[0033] Examples of antihistamines include azelastine hydrochloride, alimazine tartrate, ebastine, epinastine hydrochloride, emedastine fumarate, oxatomide, olopatadine hydrochloride, carbinoxamine, clemastine fumarate, diphenyl disulfonate, carbinoxamine maleate, d-chlorpheniramine maleate, dl-chlorpheniramine maleate, ketotifen fumarate, diphenylpyraline hydrochloride, diphenylpyraline theoclate, and diphenhydramine hydrochloride. One or more substances selected from the group consisting of diphenhydramine salicylate, diphenhydramine tannate, triprolidine hydrochloride, triperenamine hydrochloride, tondilamine hydrochloride, fexofenadine, phenetazine hydrochloride, promethazine hydrochloride, promethazine, mequitazine, methodilazine hydrochloride, loratadine, isopentyl hydrochloride, difeterol hydrochloride, methodilazine hydrochloride, mebhydroline napadisylate, promethazine methylenedisalicylic acid, and difeterol phosphate.

[0034] Examples of anti-inflammatory agents include one or more selected from the group consisting of glycyrrhizic acid and its derivatives and their salts (e.g., dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.) and tranexamic acid.

[0035] Examples of anticholinergic agents include one or more selected from the group consisting of scopolamine hydrobromide, datura extract, methylscopolamine bromide, methyl-l-hyoscyamine bromide, pirenzepine hydrochloride, butylscopolamine bromide, belladonna alkaloids, belladonna extract, total belladonna alkaloids, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide, belladonna extract, belladonna root, and total belladonna root alkaloid citrate.

[0036] Examples of vitamins include one or more selected from the group consisting of vitamin A, vitamin C, vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, vitamin P, vitamin E, hesperidin, nicotinic acid, nicotinamide, panthenol, calcium pantothenate, sodium pantothenate, biotin, potassium-magnesium aspartate equimolar mixture, inositol hexanicotinate, ursodeoxycholic acid, L-cysteine, L-cysteine ​​hydrochloride, orotin, gamma-oryzanol, calcium glycerophosphate, calcium gluconate, gluconolactone, glucuronamide, sodium chondroitin sulfate, carrot, coix seed, and iodine.

[0037] Examples of xanthine derivatives include one or more selected from the group consisting of caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine, and caffeine citrate. Examples of sedatives include at least one selected from the group consisting of allyl isopropylacetylurea and bromovalerylurea.

[0038] Furthermore, solid dosage forms may contain other components besides those mentioned above. Examples of such additives include one or more selected from the group consisting of pharmaceutically acceptable carriers, such as excipients, binders, disintegrants, disintegration aids, lubricants, fluidizers, glossing agents, foaming agents, moisture-proofing agents, surfactants, stabilizers, emulsifiers, antioxidants, fillers, preservatives, sweeteners, flavoring agents, cooling agents, fragrances, aromatics, colorants, bases, coating agents, sugar coating agents, plasticizers, dispersants, and defoaming agents. These may be, for example, conventionally known formulation additives that can be used in solid dosage forms.

[0039] Excipients include, for example, sugar powder, gum arabic, gum arabic powder, cocoa butter, caramel, sodium carboxymethyl starch, anhydrous amorphous silicon dioxide, xylitol, magnesium aluminosilicate, calcium silicate, magnesium silicate, anhydrous calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate granules, calcium monohydrogen phosphate, calcium hydrogen phosphate hydrate, calcium hydrogen phosphate granules, sodium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, sodium dihydrogen phosphate hydrate, crystalline cellulose, crystalline cellulose / carmellose sodium, crystalline cellulose (fine particles), crystalline cellulose (granules), powdered cellulose, synthetic aluminum silicate, synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose This includes one or more selected from the group consisting of wheat starch, rice flour, rice starch, heavy anhydrous silicic acid, refined sucrose, refined sucrose spherical granules, gelatin, D-sorbitol, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, dextrin, corn starch, corn starch granules, trehalose, lactose monohydrate, lactose granules, sucrose, potato starch, hydroxypropyl starch, powdered sugar, powdered candy, powdered reduced maltose syrup, powdered cellulose, pectin, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 60, maltitol, D-mannitol, magnesium aluminometasilicate, calcium sulfate, erythritol, glucose, and fructose.

[0040] Examples of binders include one or more selected from the group consisting of gum arabic, gum arabic powder, kanbai flour, gelatin, shellac, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, pullulan, povidone, polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, butyl methacrylate / methyl methacrylate copolymer, methylcellulose, and polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer.

[0041] The disintegrant is one or more selected from the group consisting of, for example, sodium carboxymethyl starch, carmellose, calcium carmellose, sodium croscarmellose, crospovidone, low-substituted hydroxypropyl cellulose, hydroxypropyl starch, partially pregelatinized starch, and sodium starch glycolate.

[0042] Examples of disintegrating agents include one or more selected from the group consisting of carboxymethyl starch sodium, carmellose, carmellose calcium, croscarmellose sodium, crystalline cellulose, sodium bicarbonate, precipitated calcium carbonate, lactose monohydrate, hydroxypropyl starch, polysorbate 40, polysorbate 60, polysorbate 80, macrogol 1500, and macrogol 4000.

[0043] Examples of lubricants include one or more selected from the group consisting of magnesium stearate, calcium stearate, talc, sucrose fatty acid esters, glycerin fatty acid esters, polyethylene glycol, hydrogenated oil, and sodium stearyl fumarate.

[0044] Examples of fluidizing agents include one or more selected from the group consisting of synthetic aluminum silicate, heavy anhydrous silicic acid, magnesium aluminum hydroxide, stearic acid, calcium stearate, magnesium stearate, tricalcium phosphate, talc, and calcium hydrogen phosphate granules.

[0045] Examples of glossing agents include one or more selected from the group consisting of carnauba wax, bleached beeswax, refined shellac, macrogol 400, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, and beeswax.

[0046] Examples of foaming agents include one or more selected from the group consisting of anhydrous sodium carbonate, tartaric acid, potassium bitartrate, sodium bicarbonate, and anhydrous citric acid.

[0047] Examples of moisture-proofing agents (excluding component (C)) include ethylcellulose, olive oil, dried aluminum hydroxide gel, glycerin, magnesium silicate, hydrogenated oil, synthetic aluminum silicate, sucrose fatty acid ester, stearic acid, magnesium stearate, refined shellac, refined sucrose, talc, neutral anhydrous sodium sulfate, precipitated calcium carbonate, a mixture of fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, and hydroxypropyl methylcellulose 2910, and polyvinyl acetal diethylaminoacetate. Moisture-proofing agents are preferably lipophilic additives.

[0048] Examples of surfactants include one or more selected from the group consisting of sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene stearyl ether, polyoxyethylene cetyl ether, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan beeswax, polyoxyethylene nonylphenyl ether, polyoxyethylene (20) polyoxypropylene (20) glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (10) polyoxypropylene (4) cetyl ether, polysorbate 20, polysorbate 60, polysorbate 80, macrogol 400, sorbitan monooleate, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, and sodium lauryl sulfate.

[0049] Examples of stabilizers include adipic acid, L-aspartic acid, sodium L-aspartate, DL-alanine, L-alanine, L-arginine, L-arginine hydrochloride, sodium alginate, propylene glycol alginate, benzoic acid, sodium benzoate, ethylenediamine, disodium calcium edetate, sodium edetate, tetrasodium edetate, tetrasodium edetate tetrahydrate, zinc chloride, ammonium chloride, calcium chloride hydrate, and cetylpyridinium chloride. Ferric chloride, sodium chloride, magnesium chloride, cysteine ​​hydrochloride, L-histidine hydrochloride, cocoa butter, carboxyvinyl polymer, carmellose calcium, carmellose sodium, anhydrous sodium carbonate, glycine, glycerin, glycerin fatty acid ester, calcium gluconate hydrate, sodium gluconate, magnesium gluconate, potassium L-glutamate, sodium L-glutamate, L-lysine L-glutamate, sodium dihydrogen phosphate, chondroitin sulfate L-Cystine, L-Cysteine, Tartaric Acid, Sucrose Fatty Acid Ester, Stearic Acid, Purified Gelatin, Purified Soy Lecithin, Gelatin, Gelatin Hydrolyzate, Sorbitan Fatty Acid Ester, Taurine, Talc, Calcium Carbonate, Potassium Bicarbonate, Sodium Bicarbonate, Sodium Carbonate Hydrate, Magnesium Carbonate, Natural Vitamin E, Tocopherol, Tocopherol Acetate, Lactose, Concentrated Glycerin, Povidone, Polyoxyethylene Hydrogenated Castor Oil 60, Polyoxyethylene Stearic Acid Polyoxyethylene cetyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene (42) polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene coconut oil fat glyceryl (7E.O.)Examples include polysorbate 20, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), macrogol 300, macrogol 400, macrogol 4000, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium monohydrogen phosphate, anhydrous sodium dihydrogen phosphate, methylcellulose, l-menthol, glyceryl monostearate, medicinal charcoal, magnesium sulfate hydrate, DL-malic acid, sodium hydrogen phosphate hydrate, potassium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, L-leucine, and one or more selected from the group consisting of polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer.

[0050] Examples of emulsifiers include one or more selected from the group consisting of glycerin fatty acid esters, propylene glycol fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyethylene glycol fatty acid esters, and hydrogenated soybean phospholipids.

[0051] Examples of antioxidants include one or more selected from the group consisting of ascorbic acid, L-ascorbic acid stearate, citric acid hydrate, soy lecithin, natural vitamin E, tocopherol, tocopherol acetate, ascorbic palmitate, and sodium pyrosulfite.

[0052] Examples of fillers include one or more selected from the group consisting of RSS No. 1 raw rubber, starch acrylate 1000, titanium dioxide, and calcium monohydrogen phosphate.

[0053] Examples of preservatives include one or more selected from the group consisting of benzoic acid, sodium benzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, methyl parahydroxybenzoate, dehydroacetic acid, sodium dehydroacetate, sorbic acid, and phenoxyethanol.

[0054] Examples of sweeteners (excluding ingredient (B)) include one or more selected from the group consisting of aspartame, acesulfame potassium, hydrangea, hydrangea powder, reduced maltose syrup, xylitol, saccharin, saccharin sodium hydrate, sucralose, stevia extract, stevia extract, refined sucrose, fructose, sucrose, maltitol, D-mannitol, and erythritol.

[0055] Examples of flavoring agents include one or more selected from the group consisting of sodium chloride, orange, orange oil, cocoa powder, fructose, caramel, xylitol, calcium citrate, citric acid hydrate, sodium citrate hydrate, L-glutamic acid, sodium L-glutamate, grapefruit extract, brown sugar, saccharin, sodium saccharin hydrate, tartaric acid, D-tartaric acid, potassium bitartrate, DL-sodium tartrate, sucralose, stevia extract, stevia extract, swertia japonica, D-sorbitol, tannic acid, trehalose hydrate, fructooligosaccharides, powdered sugar, peppermint powder, D-mannitol, dl-menthol, l-menthol, menthol powder, green tea powder, DL-malic acid, DL-sodium malate, lemon oil, and rose oil.

[0056] Examples of cooling agents include one or more selected from the group consisting of fennel oil, d-camphor, dl-camphor, cinnamon oil, peppermint water, peppermint oil, and l-menthol.

[0057] Examples of flavorings include one or more selected from the group consisting of orange flavor, guarana extract, sweet orange, strawberry, brown sugar flavor, cherry flavor, banana powder flavor, peach essence, fruit essence, peppermint, melon powder flavor, l-menthol, and peppermint oil.

[0058] Examples of fragrances include one or more selected from the group consisting of fennel powder, fennel oil, ethyl vanillin, d-camphor, dl-camphor, spearmint oil, turpentine oil, pineapple powder fragrance 51357, pineapple powder fragrance 59492, peppermint water, peppermint oil, vanilla powder fragrance 54286, vanillin, bergamot oil, d-borneol, dl-borneol, dl-menthol, l-menthol, eucalyptus oil, rose water, and rose oil.

[0059] Examples of colorants include one or more selected from the group consisting of yellow iron oxide, yellow ferric oxide, orange essence, brown iron oxide, carbon black, caramel, β-carotene, gold leaf, black iron oxide, titanium dioxide, ferric oxide, dizazo yellow, food blue No. 1, food yellow No. 4, food yellow No. 5, food blue No. 2 aluminum lake, food yellow No. 4 aluminum lake, food red No. 2, food red No. 3, food red No. 102, ferric oxide / glycerin suspension, copper chlorophyllin sodium, copper chlorophyll, phenol red, malachite green, methylene blue, medicinal charcoal, riboflavin, riboflavin butyrate, riboflavin phosphate sodium, green tea powder, and rose oil.

[0060] The base ingredients include, for example, acacia gum powder, pregelatinized starch, ethylcellulose, cocoa butter, carnauba wax, carboxyvinyl polymer, carmellose, carmellose sodium, reduced maltose syrup, dried aluminum hydroxide gel, agar, agar powder, xanthan gum, glycine, glycerin, glycerin fatty acid ester, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, synthetic magnesium sodium silicate, titanium dioxide, tartaric acid, sucrose fatty acid ester, silicone oil, stearic acid, magnesium stearate, gelatin, D-sorbitol, talc, calcium carbonate, corn starch, lactic acid, ethyl lactate, calcium lactate hydrate, lactic acid / glycolic acid copolymer, concentrated glycerin, potato starch, hydroxypropylcellulose, hyp Examples include romerose, pullulan, pectin, povidone, polysorbate 60, polysorbate 80, polyvinyl alcohol (partially saponified), microcrystalline wax, macrogol 200, macrogol 300, macrogol 400, macrogol 1000, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 6000NF, macrogol 20000, D-mannitol, glyceryl monostearate, sorbitan monostearate, batyl monostearate, propylene glycol monostearate, polyethylene glycol monostearate, sodium lauryl sulfate, and one or more selected from the group consisting of polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer.

[0061] Examples of coating agents include: ethyl acrylate / methyl methacrylate copolymer dispersion, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, gum arabic, gum arabic powder, ethyl cellulose, ethyl cellulose aqueous dispersion, carnauba wax, carboxyvinyl polymer, gold leaf, silver leaf, triethyl citrate, glycerin, glycerin fatty acid ester, hydrogenated oil, titanium dioxide, sucrose fatty acid ester, stearyl alcohol, stearic acid, magnesium stearate, purified gelatin, purified shellac, gelatin, D-sorbitol, talc, calcium carbonate, magnesium carbonate, medium gold leaf, precipitated calcium carbonate, concentrated glycerin, white shellac, hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose 2910 / titanium dioxide / macrogol 400 mixture, hypromellose, fumaric acid / stearic acid / polyvinyl acetal diethylaminoacetate / hydroxypropyl methylcellulose Examples include one or more selected from the group consisting of polycellulose 2910 mixture, pullulan, polysorbate 80, polyvinyl acetal diethylaminoacetate, povidone, polyvinyl alcohol (partially saponified), macrogol 300, macrogol 400, macrogol 600, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 6000NF, macrogol 20000, macrogol 35000, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, magnesium aluminometasilicate, methyl acrylate / methacrylic acid / methyl methacrylate copolymer, methylcellulose, 2-methyl-5-vinylpyridine methyl acrylate / methacrylic acid copolymer, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, calcium sulfate, and polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer.

[0062] Examples of sugar coating agents include one or more selected from the group consisting of gum arabic, gum arabic powder, ethylcellulose, carnauba wax, carboxymethylcellulose sodium, titanium dioxide, stearic acid, polyoxyl 40 stearate, purified gelatin, purified shellac, purified sucrose, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, sucrose, hydroxypropylcellulose, hypromellose, pullulan, povidone, polyvinyl alcohol (partially saponified), macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, calcium hydrogen phosphate hydrate, calcium dihydrogen phosphate hydrate, and polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer.

[0063] Examples of plasticizers include one or more selected from the group consisting of triethyl citrate, glycerin, glycerin fatty acid esters, D-sorbitol, medium-chain triglyceride, triacetin, concentrated glycerin, castor oil, polyoxyethylene hydrogenated castor oil 60, propylene glycol, polyoxyethylene (105) polyoxypropylene (5) glycol, polysorbate 80, macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, macrogol 6000, macrogol 6000NF, glyceryl monostearate, isopropyl linoleate, and liquid paraffin.

[0064] Examples of dispersants include aminoalkyl methacrylate polymer RS, gum arabic, gum arabic powder, carboxyvinyl polymer, sodium carboxymethyl starch, agar powder, citric acid hydrate, sodium citrate hydrate, glycerin, glycerin fatty acid ester, magnesium silicate, light aluminum oxide, crystalline cellulose, titanium dioxide, sucrose fatty acid ester, stearic acid, magnesium stearate, D-sorbitol, soy lecithin, low-substituted hydroxypropyl cellulose, dextrin, corn starch, lactose hydrate, concentrated glycerin, potato starch, hydroxyethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hypromellose, povidone, polyoxy One or more substances selected from the group consisting of ethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polysorbate 20, polysorbate 60, polysorbate 80, microcrystalline wax, macrogol 300, macrogol 4000, macrogol 6000, macrogol 6000NF, anhydrous sodium citrate, magnesium aluminometasilicate, methylcellulose, glyceryl monooleate, sorbitan monooleate, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, sorbitan monopalmitate, sorbitan monolaurate, and sodium lauryl sulfate.

[0065] Examples of defoaming agents include one or more selected from the group consisting of ethanol, glycerin fatty acid esters, dimethylpolysiloxane (for oral use), sucrose fatty acid esters, silicone defoaming agents, silicone oils, sorbitan fatty acid esters, and polysorbate 80.

[0066] (First container) The first container is preferably at least one container selected from the group consisting of bottles (glass bottles, etc.), cans, resin bottles (synthetic resin bottles, natural resin bottles, etc.), PTP (Press Through Package) containers, SP (Strip Package) containers, and paper containers. This makes the storage stability of the solid dosage form more suitable. In this case, the solid dosage form preferably has a solid composition containing components (A) and (B), and component (C) is in the first container but outside the solid composition. Other examples of the first container include pouch packaging containers, stick packaging containers, pillow packaging containers, boxes (for example, solid packaging boxes), etc.

[0067] The type and constituent materials of the first container can be selected, for example, according to the form of the composition containing components (A) and (B), and may be selected from known solid dosage form packaging containers. Furthermore, the first container is preferably an airtight container. This makes it possible to more stably suppress discoloration caused by the combination of components (A) and (B).

[0068] Materials used in SP containers, PTP containers, stick packaging containers, pillow packaging containers, etc., include, for example, resin films such as polypropylene film, polyethylene terephthalate film, and polyethylene film, as well as resin films to which aluminum foil is attached. Either single-layer films or multi-layer films (e.g., laminate films) may be used.

[0069] Furthermore, it is preferable that the constituent materials of the first container include materials that are less susceptible to the effects of moisture. Examples of such containers include packaging containers formed from at least one of a moisture-proof material and a gas barrier material. Examples of moisture-proof materials include a combination of PTP (polypropylene) and polyethylene aluminum pillow. Furthermore, when the solid dosage form contains tablets which are solid compositions containing components (A) and (B), a PTP (Al-Al packaging) container with aluminum on both sides may be used as a moisture-proof material, taking into consideration the suppression of the rise in moisture content in the tablets, the storage stability of the tablets, and the stability of the tablets after opening. Known materials may be used as the gas barrier material, for example, a laminate film having a functional barrier layer, and may be used to serve the same purpose as the moisture barrier material, or in combination with the moisture barrier material.

[0070] Furthermore, at least a portion of the first container may be made environmentally friendly. For example, environmentally friendly materials such as recycled plastic, biomass plastic, or biodegradable plastic may be used in part or all of the first container.

[0071] The solid dosage form may be, for example, an oral composition, or a composition for oral use. Alternatively, the solid dosage form may be, for example, a pharmaceutical composition. This allows for a more favorable attainment of the desired efficacy. The following provides a more detailed explanation of examples of solid dosage form compositions.

[0072] (First embodiment) In this embodiment, the solid formulation can have, for example, a solid composition containing components (A) and (B), with component (C) located outside the solid composition in the first container. This allows for greater flexibility in the formulation of the solid composition while stably suppressing discoloration.

[0073] The dosage form of the solid composition may be, for example, a preparation for oral administration (including tablets, orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolvable tablets, capsules, pills, powders, granules, fine granules, etc.) or a preparation for application in the oral cavity (including oral tablets, lozenges, sublingual tablets, buccal tablets, adhesive tablets, gums, etc.), as described in the General Provisions for Preparations of the 18th Edition of the Japanese Pharmacopoeia. The solid composition may be coated by known methods such as sugar coating or film coating, as needed.

[0074] The dosage form of the solid composition is preferably one selected from the group consisting of tablets, orally disintegrating tablets, chewable tablets, powders, capsules, and granules. This makes it easier to take orally. Specific examples of tablets include uncoated tablets, film-coated tablets, and sugar-coated tablets.

[0075] Since the solid composition contains components (A) and (B), it can provide one or more effects selected from the group consisting of reducing inflammation such as rhinitis and reducing various symptoms of the common cold. Furthermore, the solid composition is preferably a pharmaceutical composition, and more preferably a rhinitis treatment or a cold medicine.

[0076] Next, we will explain the color properties of the solid composition. The color difference ΔE of the solid composition before and after storage is measured by the following method and obtained by the following formula (I). * This value may be, for example, 22 or less, preferably 20 or less, more preferably 18 or less, and even more preferably 15 or less. This makes it possible to more effectively suppress changes in the visible appearance color. Furthermore, the color difference ΔE of the solid composition before and after storage obtained by formula (I) * For example, it may be 0.1 or greater, or it may be 1.0 or greater.

[0077] ΔE * ={(L * 2-L * 1) 2 +(a * 2-a * 1) 2 +(b * 2-b * 1) 2} 1 / 2 (I) (In the above formula (I), (L * 1,a * 1,b *1) and (L * 2,a * 2,b * 2) The CIE1976L standards apply to the solid composition before storage and after storage at 60°C for one month. * a * b * These are chromaticity coordinates defined by a color system.

[0078] (method) The solid dosage form was stored in a sealed state at 60°C for one month. Each sample before and after storage was measured using a spectrophotometer under the following conditions in accordance with JIS Z 8722, and the CIE1976L was determined based on the measured values. * a * b * Obtain the chromaticity coordinates defined by the color system, and the color difference ΔE * We seek. • Colorimeter conditions: Measurements were taken using the "reflection" measurement conditions of a spectrophotometer (e.g., model SE7700, manufactured by Nippon Denshoku Industries Co., Ltd.). • Measurement sample: The solid composition was packed into a round cell case with a diameter of 35 mm and a height of 15 mm for measurement.

[0079] In the above method, the sample to be measured can be prepared, for example, according to the properties of the solid composition. If the solid composition is in powder form, for example, the solid composition can be packed into the round cell case and measured. Also, if the sample to be measured is in a state other than powder (for example, a tablet), for example, the tablet may be crushed into a powder, and then the solid composition may be packed into the round cell case and measured, or the tablet may be placed on a sample stage with a diameter of 6 mm and the reflected light measured. Furthermore, regarding the number of measurements, for example, one sample may be measured only once.

[0080] The Δb of the solid composition before and after storage is obtained from the chromaticity coordinates measured by the above method using the following formula (II). * This is preferably 17.0 or less, more preferably 10.0 or less, and even more preferably 5.0 or less. This makes it possible to more reliably improve the storage stability of the solid composition. Also, Δb * This could be, for example, 1.0 or greater, or 2.0 or greater. Δb * =b * 2-b * 1 (II)

[0081] From the chromaticity coordinates measured by the above method, the Δ(a) of the solid composition before and after storage is obtained using the following formula (III). * +b * The ratio is preferably 17.5 or less, more preferably 10.0 or less, and even more preferably 5.0 or less. This makes it possible to more reliably improve the storage stability of the solid composition. Also, Δ(a * +b * ) may be, for example, 1.0 or greater, or 2.0 or greater. Δ(a * +b * )=(a * 2-a * 1) + (b * 2-b * 1) (III)

[0082] In this embodiment, component (C) is preferably in tablet or particulate form, and more preferably in tablet or particulate silica gel form. Furthermore, the first container can be selected from those described herein, depending on the dosage form and components of the solid composition.

[0083] The following description will focus on the differences from the first embodiment. The configurations of each embodiment can also be combined as appropriate.

[0084] (Second Embodiment) This embodiment relates to a package in which a solid preparation containing components (A) and (B) in a second container and the following component (C) desiccant are contained in a first container. This embodiment is similar to the first embodiment in that both the solid dosage form and component (C) are contained in the first container, but differs from the first embodiment in that component (C) is located outside the second container in which the solid dosage form is contained. In this embodiment, as in the first embodiment, the degree of freedom in formulating the solid composition can be increased while stably suppressing discoloration. Furthermore, in this embodiment, by housing the solid formulation in a second container, the deterioration of quality during transportation and handling of the solid composition can be suppressed more reliably.

[0085] The composition of the solid composition containing components (A) and (B), and the composition of component (C), can be as described above in the first embodiment, for example.

[0086] The second container can be selected, for example, from those described herein, depending on the dosage form and components of the solid composition, and the first container may be selected from those mentioned above, or more specifically, from the group consisting of PTP containers, SP containers and paper containers.

[0087] The first container can be selected from, for example, those described above in this specification, depending on the type and size of the second container and the properties and size of component (C), for example, from the group consisting of pillow containers and solid packaging boxes. This effectively suppresses external influences during transportation and storage.

[0088] (Third embodiment) This embodiment relates to a solid composition containing components (A) to (C). The solid composition may preferably be contained in a first container to constitute a solid formulation, and more preferably the first container is sealed. In this embodiment as well, by having the solid formulation contain components (A) to (C) in the first container, components (A) and (B) can be stably incorporated into the solid composition, and discoloration of the solid composition can be suppressed. Furthermore, according to this embodiment, it is possible to miniaturize and thin the entire solid formulation, including the first container.

[0089] The composition of the solid composition containing components (A) and (B) can be, for example, the configuration described above in the first embodiment.

[0090] Furthermore, component (C) can be selected from, for example, the aforementioned desiccants, and it is preferable that it be a component and has properties that are easily uniformly incorporated into the solid composition. In this regard, component (C) is preferably in powder form, and more preferably one or more selected from the group consisting of silica gel, silica alumina gel (allophene), calcium chloride, zeolite, quicklime, bentonite clay (montmorillonite), magnesium chloride, and magnesium oxide, in powder form.

[0091] The content of component (C) in the solid composition per day is preferably 0.01% by mass or more, and more preferably 0.1% by mass or more, relative to the total solid composition. This makes it possible to more reliably obtain the discoloration suppression effect. Furthermore, the content of component (C) in the solid composition per day is preferably 10% by mass or less, and more preferably 5% by mass or less, relative to the total solid composition. This allows for miniaturization of the solid composition and more efficiently obtaining the discoloration suppression effect.

[0092] Regarding the configuration of the first container, for example, the configuration described above can be used in the first embodiment.

[0093] (Manufacturing method) Next, we will explain the manufacturing method of solid dosage forms. A method for producing a solid dosage form may include, for example, a step of placing components (A) to (C) into a first container. Furthermore, the method for producing a solid dosage form may further include a step of sealing the first container after the step of placing the components into the first container. The procedure for placing components (A) to (C) into the first container can be determined, for example, depending on the composition of the solid composition to be placed in the first container.

[0094] For example, when manufacturing a solid dosage form according to the first embodiment described above, the method may include, for example, the steps of preparing a solid composition containing components (A) and (B), and placing the solid composition and component (C) into a first container.

[0095] When manufacturing the packaging according to the second embodiment described above, the method may include, for example, the steps of: preparing a solid composition containing components (A) and (B); placing the solid composition in a second container to obtain a solid formulation; and placing the solid formulation and component (C) in a first container to obtain a packaging.

[0096] Furthermore, when producing the solid composition of the third embodiment described above, the method may include, for example, a step of preparing a solid composition containing components (A) to (C), and may further include a step of placing the solid composition into a first container.

[0097] The embodiments of the present invention have been described above, but these are merely examples, and various other configurations can also be adopted. [Examples]

[0098] The embodiment will be described in detail below with reference to examples, but this embodiment is not limited to these examples.

[0099] (Examples 1-14, Comparative Examples 1-13, Reference Examples 1-14) The solid dosage forms for each case were prepared and evaluated using the following method.

[0100] (Preparation of solid dosage forms) Each component was weighed out to a total of 3g according to the proportions listed in Tables 1 to 7, and the mixed powder was prepared by mixing in a bag, sieving (mesh size 500μm), and mixing in a bag again. One g of the prepared mixed powder was weighed into a clear 3K bottle (the first container), sealed tightly, and used as the sample. For samples containing a desiccant, the required amount of the following desiccant was added, the bottle was sealed tightly, and used as the sample. Desiccant: PW-1506 manufactured by Yamajin Pharmaceutical Co., Ltd., weight per unit: 1.13g In each table, for the examples where desiccant is added "yes," if there is no specific mention of the amount of desiccant, one PW-1506 desiccant was added. In the example where half a desiccant was used, the above-mentioned desiccant PW-1506 was divided into 0.57g portions and added. Similarly, in the example using 1 / 4 of a desiccant, the above-mentioned desiccant PW-1506 was divided into 0.28g portions and added. Similarly, in the example where the amount of desiccant was doubled, two units of the above-mentioned desiccant PW-1506 were added.

[0101] (Evaluation using a colorimeter) The samples obtained from each case were stored at 60°C in a tightly sealed container for one month. Chromatic coordinates (L) of the sample before and after storage * a * , b * The ΔE between the sample before and after storage was measured using a colorimeter (spectrophotometer (model SE7700): manufactured by Nippon Denshoku Industries), and the ΔE between the sample before and after storage was calculated using the following formula (I). * (L * a * b * The value defined by the distance between coordinates in the color system was calculated. Also, Δb * and Δ(a * +b * The results were obtained. The results are shown in each table. ΔE * ={(L * 2-L * 1) 2 +(a * 2-a * 1) 2 +(b * 2-b * 1) 2} 1 / 2 (I)

[0102] The color measurement conditions are as follows. • Measurement equipment and conditions: Measurements were taken using a spectrophotometer (model SE7700, manufactured by Nippon Denshoku Industries Co., Ltd.) under the "reflection" measurement conditions. • Measurement sample: The mixed powder for each example was packed into a round cell case with a diameter of 35 mm and a height of 15 mm for measurement. • Number of measurements: One measurement per sample.

[0103] (Visual evaluation) For the samples used for evaluation with a colorimeter, the degree of discoloration of the stored samples compared to the unstored samples was visually assessed according to the following criteria. The evaluation results are shown in the respective tables. ++: Severe discoloration +: Discoloration present (turned brown) ±: Slight discoloration (discoloration is visible to the naked eye) -: No discoloration (discoloration is not visible to the naked eye)

[0104] The raw materials used in each example are shown below. Levocetirizine hydrochloride: Manufactured by SperaNexus. Cetirizine dihydrochloride: Manufactured by LKT Laboratories, Inc. Dipotassium glycyrrhizinate: Manufactured by Alps Pharmaceutical Co., Ltd. Ammonium glycyrrhizinate: Manufactured by Alps Pharmaceutical Co., Ltd., Ammonium glycyrrhizinate A "Alps" Tranexamic acid: Manufactured by Kyowa Pharma Chemical Co., Ltd. Magnesium aluminometasilicate: Manufactured by Fuji Chemical Industry Co., Ltd., Noisilin FL2 Hydrated silicon dioxide: Manufactured by Fuji Silysia Chemical Co., Ltd., SYLYSIA 320 Licorice extract: Maruzen Pharmaceutical Co., Ltd. Piarex

[0105] [Table 1]

[0106] [Table 2]

[0107] [Table 3]

[0108] [Table 4]

[0109] [Table 5]

[0110] [Table 6]

[0111] [Table 7]

[0112] Tables 1 to 7 show that in reference examples containing one of components (A) and (B) but not the other, the degree of discoloration was small even when component (C) was not present in the same container. Furthermore, in reference examples containing tranexamic acid and one of components (A) and (B) but not the other component (A) and (B), the degree of discoloration was also small. In contrast to these reference examples, the compositions of each comparative example, which contained components (A) and (B) in the container but did not contain component (C), underwent discoloration after storage at 60°C and 1M. Furthermore, in the example in which components (A) to (C) were contained in a single container, discoloration after storage was suppressed compared to a comparative example composition in which the amounts of components (A) and (B) per single dose were the same but component (C) was not included. In Table 1, discoloration after storage was suitably suppressed in Examples 1 to 3. Specifically, in Examples 1, 2, and 3, discoloration after storage was suppressed compared to Comparative Examples 1, 2, and 3, which had the same amounts of components (A) and (B), respectively. Furthermore, the discoloration suppression effect in Example 2 was more pronounced compared to cases where magnesium aluminometasilicate or silicic acid was included in the same container instead of component (C) (Comparative Examples 4 and 5). In addition, a discoloration suppression effect was observed in Examples 11 to 13, in which the amount of desiccant in Example 2 was varied, compared to Comparative Example 2 (Table 6). In Table 2, Examples 4, 5, and 6 showed suppressed discoloration after storage compared to Comparative Examples 6, 7, and 8, respectively. In Tables 3 and 5, Examples 7, 8, 9, and 10 showed suppressed discoloration after storage compared to Comparative Examples 9, 10, 11, and 12, respectively. From Table 7, even when component (B) was component (B2), Example 14 showed suppressed discoloration after storage compared to Comparative Example 13. Furthermore, as shown in Table 4, when component (A) and tranexamic acid were present together, no discoloration was observed under the aforementioned storage conditions, regardless of the presence or absence of a desiccant.

Claims

1. A solid preparation containing the following ingredients (A) to (C) in the first container. (A) At least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. (B) At least one selected from the group consisting of the following components (B1) and (B2) (B1) At least one selected from the group consisting of glycyrrhizic acid, its salts and their hydrates. (B2) At least one selected from the group consisting of licorice and its extracts. (C) Desiccant

2. The solid preparation comprises a solid composition containing the components (A) and (B), The solid formulation according to claim 1, wherein the component (C) is located outside the solid composition in the first container.

3. The solid preparation according to claim 2, wherein the dosage form of the solid composition is one selected from the group consisting of tablets, orally disintegrating tablets, chewable tablets, powders, capsules, and granules.

4. The solid formulation according to claim 2, wherein the solid composition is a pharmaceutical composition.

5. The solid formulation according to claim 2, wherein the solid composition is a treatment for rhinitis.

6. The solid formulation according to claim 2, wherein the solid composition is a cold medicine.

7. The amount of component (A) in the solid composition per day is 1 mg or more and 20 mg or less. The solid preparation according to claim 2, wherein the amount of component (B) in the solid composition per day is 1 mg or more and 300 mg or less.

8. The solid preparation according to claim 2, wherein the mass ratio of the content of component (A) to the total amount of components (A) and (B) in the solid composition ((A) / ((A) + (B))) is 0.01 or more and 0.9 or less.

9. The solid preparation according to claim 2, wherein in one of the first containers, the mass ratio of the content of component (A) to the total amount of components (A) and (C) ((A) / ((A) + (C))) is 0.005 or more and 0.35 or less.

10. The solid preparation according to claim 2, wherein the first container is at least one container selected from the group consisting of bottles, cans, synthetic resin bottles, PTP containers, SP containers, paper containers, and natural resin bottles.

11. The color difference ΔE of the solid composition before and after storage is measured by the following method and obtained by the following formula (I). * The solid preparation according to claim 2, wherein the amount is 20 or less. (method) The solid dosage form was stored in a sealed state at 60°C for one month. Each sample before and after storage was measured using a spectrophotometer under the following conditions in accordance with JIS Z 8722, and based on the measured values, CIE1976L * a * b * Obtain the chromaticity coordinates defined by the color system, and the color difference ΔE * We seek. ΔE * ={(L * 2-L * 1) 2 +(a * 2-a * 1) 2 +(b * 2-b * 1) 2 } 1 / 2 (I) (In the above formula (I), (L * 1, a * 1, b * 1) and (L * 2, a * 2, b * 2) The CIE 1976L of the solid composition before storage and after storage at 60°C for one month. * a * b * These are chromaticity coordinates defined by a color system.

12. A solid preparation containing the following components (A) and (B) in a second container, The following component (C), A package containing the first container. (A) At least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. (B) At least one selected from the group consisting of glycyrrhizic acid, its salts and their hydrates. (C) Desiccant

13. The packaging according to claim 12, wherein the first container is at least one selected from the group consisting of pillow containers and individual packaging boxes.

14. A solid composition comprising the following components (A) to (C). (A) At least one selected from the group consisting of cetirizine, its optical isomers, and salts thereof. (B) At least one selected from the group consisting of glycyrrhizic acid, its salts and their hydrates. (C) Desiccant

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